Оптические сенсоры для анализа жидких сред на основе комбинации фотонных интегральных схем и микрофлюидных устройств (Optical sensors for liquid analysis based on a combination of photonic integrated circuits and microfluidic devices) тема диссертации и автореферата по ВАК РФ 00.00.00, кандидат наук Кузин Алексей Юрьевич

• Кузин Алексей Юрьевич
• кандидат наук
• 2025

Оглавление диссертации кандидат наук Кузин Алексей Юрьевич

TABLE OF CONTENTS

Introduction

Chapter 1. Literature review and problem statement

1.1 Photonic integrated circuits

1.1.1 Optical waveguide

1.1.1.1 Refractive index theory in dielectric media

1.1.1.2 Photonic waveguide sensors

1.1.2 Microring resonator

1.1.3 Mach-Zehnder interferometer

1.1.4 Speckle spectrometer and demultiplexer

1.1.5 Coupling elements for input and output of optical radiation

1.1.6 Platforms and fabrication capabilities

1.2 Multiscale fluidics

1.2.1 Fluid behavior at diverse length scales: milli, micro, and nano

1.2.2 Modern applications of microfluidics

1.3 Lab-on-a-chip sensors based on combination PICs and MFCs

1.3.1 Biomarkers (i)

1.3.2 Biorecognition elements (ii)

1.3.2.1 Physical adsorption

1.3.2.2 Physical entrapment

1.3.2.3 Covalent immobilization

1.3.2.4 Non-covalent immobilization (streptavidin-biotin system)

1.3.2.5 Biorecognition elements for silicone-based surface

1.3.3 Sensor and output signal (iii-iv)

1.3.3.1 Refractive index sensors for environmental and fluid monitoring

1.3.3.2 Nanophotonic-microfluidic sensors for liquid biopsy applications

1.4 Research object selection and task definition

Chapter 2. Development, fabrication and measurement methodology of a hybrid

nanophotonic-microfluidic sensor platform

2.1 Fabrication protocol and characterization of photonic chip

2.1.1 Determination waveguide width

2.1.2 Refractive index profiling of the chip topology

2.2 Fabrication protocol of microfluidic chip

2.3 Integration of photonic and microfluidic chips

2.4 Experimental setup and measurement methodology

2.5 Methods for nanophotonic-microfluidic sensor characterization

2.5.1 Methods for thermal control of PICs including microheater performance and stabilization techniques

2.5.2 Characterization method for MZI-based sensors

2.5.3 Characterization method for MRR-based sensors

2.5.4 Characterization method for speckle demultiplexer-based sensors

2.5.5 Spectral data processing and analysis method

2.6 Methods for isolation and characterization of sEVs from cell culture media

2.7 Methods of DARPin production and chip surface modification

2.8 Conclusion

Chapter 3. Photonic integrated circuits combined with microfluidics

3.1 Interaction of evanescent waveguide mode with analytes in microfluidic channels

3.2 On-chip Mach-Zehnder interferometer coupled with microfluidics

3.3 On-chip microring resonator coupled with microfluidics

3.4 On-chip robust speckle demultiplexer coupled with microfluidics

3.5 Investigating performance limitations in a developed nanophotonic-microfluidic sensor platform

3.5.1 Optical coupling efficiency

3.5.2 Propagation losses

3.5.3 Temperature fluctuations in the medium and analyte, and flow rate control stability

3.5.4 Thermal influence of heating contacts

3.5.5 Spectral resolution

3.6 Conclusion

Chapter 4. Microfluidic-nanophotonic sensor for on-chip analysis of complex

refractive index

4.1 Utilizing the near-infrared spectral band for advanced spectroscopy

4.2 Kramers-Kronig Relations for C-band

4.3 Optimizing PIC and MFC design through simulation for enhanced performance

4.4 Nanophotonic-microfluidic sensor based on microring resonator for on-chip analysis of

complex refractive index

4.4.1 Extraction of complex refractive index

4.5 Conclusion

Chapter 5. Applications of developed microfluidic-nanophotonic platform for

advanced sensing and analysis analysis

5.1 In situ monitoring of layer-by-layer assembly surface modification of nanophotonic-

microfluidic sensor

5.2 Breast cancer detection based on specific exosomes as markers

5.2.1 Molecular classification of breast cancer

5.2.2 HER2 in breast cancer

5.2.3 Tumor progression and exosomes

5.3 Real-time functionalization of a nanophotonic sensor for liquid biopsy

5.3.1 Isolation and characterization of sEVs from cell culture media

5.3.2 Specific detection of HER2-positive exosomes

5.3.3 Validation of specific sEVs detection

5.4 Conclusion

Conclusions

Acknowledgments

List of Abbreviations

Bibliography

List of Figures

List of Tables

Введение диссертации (часть автореферата) на тему «Оптические сенсоры для анализа жидких сред на основе комбинации фотонных интегральных схем и микрофлюидных устройств (Optical sensors for liquid analysis based on a combination of photonic integrated circuits and microfluidic devices)»

Introduction

In recent years, optical sensors have emerged as powerful analytical tools with a wide range of applications. When implemented with ultra-small sample volumes while maintaining potential for device modification and scaling, these sensors offer significant value for applications ranging from food quality control and medical diagnostics to pharmaceutical development, petrochemical analysis, and beyond. In this regard, there is an increasing demand for promising sensing methods that can lead to more accurate and cost-effective devices with shorter acquisition times and require only a small sample volume [1,2]. Furthermore, one of the most pressing challenges in modern medicine today is the development of fast, compact, and affordable diagnostic tools for the early detection of diseases. As one of the deadliest diseases worldwide, cancer accounts for 16.8 % of all deaths and 22.8 % fatalities caused by non-communicable diseases [3]. The most common types of cancer are breast, lung, colorectal, and prostate cancer [4]. Many cancers can be successfully treated if detected early [5]. However, there is a significant difference in the availability of treatment between countries with different income levels [6]. According to reports [7], comprehensive treatment is available in more than 90 % of high-income countries, but less than 15 % of low-income countries. Thus, one of the most pressing issues in medicine is finding fast, convenient, and affordable ways to diagnose conditions and detect oncological and other diseases in the human body at an early stage. By replacing traditional tissue biopsies with the analysis of bodily fluids or exhaled gases, the risk of spread and metastasis can be significantly reduced, thereby preserving the quality of life for patients [8]. In this regard, two main approaches can be used independently to address this issue: liquid biopsy [9,10] of biological fluids and gas biopsy [11] using exhaled air. A liquid biopsy approach involves analyzing venous blood, saliva, or urine samples instead of tumor tissue, allowing a wider range of patients to be tested. This approach also allows the early detection of diseases and helps assess the effectiveness of both chemotherapy and surgery. Also, it should be noted that a crucial component of liquid biopsy is the ability to perform highly sensitive, quantitative analysis of specific markers in real-time using microliter volumes of the biological fluid being studied.

The relevance of the research area of this dissertation work is due, on the one hand, to the pressing need to develop highly sensitive strategies for determining the chemical composition and concentration of solution components, precision control of surface modification with molecules providing required specificity, as well as for determining the concentration of exosomal markers, which could significantly improve the prognosis and treatment of cancer and other diseases, and on the other hand, to the notable gap in the availability of advanced optical sensors for realtime liquid analysis, enabling refractometric analysis with enhanced sensitivity, minimal analyte volume requirements, rapid data processing, and noise immunity, making them ideal for specialized applications.

The degree of the research area development. To address the aforementioned challenges, the development of a fully functional sensor platform requires the integration of four key components: (i) the analyte, (ii) a biorecognition element, (iii) a transducer/sensor, and (iv) a signal output system.

(i) Biomarkers such as proteins, ribonucleic acid (RNA), deoxyribonucleic acid (DNA), and

other molecules provide critical insights into biological systems and human health [12]. These markers can be found in extracellular vesicles (EVs), which are nanosized lipid particles that carry biological material between cells [13]. EVs were first found in 1946 by Chargaff and West [14] and were divided into three categories based on their size: apoptotic bodies (1-5 pm), microvesicles (150 nm-1 pm), and exosomes (30 nm - 150 nm) [15]. About 20 years ago, it was discovered that EVs play a crucial role in cellular communication and can be used to monitor the condition of cells and tissues [16]. Among all EVs, exosomes or small extracellular vesicles (sEVs), are secreted by cells from various tissues and organs into the intercellular space, are particularly important for theranostic applications [17]. Exosomes contain important biological markers, including membrane proteins and nucleic acids [18]. Moreover, specific markers found in exosomes can be used in a liquid biopsy approach to detect the presence of certain diseases [19]. For instance, the overexpression of a specific receptor in exosomes called the human epidermal growth factor receptor 2 (HER2) has been linked to human breast cancer in 20-30 % of cases [20]. Recent studies have shown that exosomes can be found in various body fluids, including blood [21], semen [22], saliva [23], plasma [24], urine [25], cerebrospinal fluid [26], amniotic fluid [27], bronchoalveolar lavage [28], synovial [29], breast milk [30], epididymal fluid [31], and in tears [32]. By analyzing the level of this marker in blood or other body fluids, doctors can detect the presence or absence of cancer and monitor its progression [33] and evaluate treatment efficiency [34]. To date, there exists only one FDA-approved liquid biopsy test based on analysis of RNA markers (ERG, PCA3, and SPDEF) contained in EVs isolated from patient urine. This test is intended for assessing the risk of high-grade prostate cancer (HGPCa) in men aged 50 years and older who have prostate-specific antigen (PSA) levels of 2-10 ng/mL [35]. Thus, the presence of specific exosomes produced by tumor cells can be used as a marker for cancer, and their quantity can be used to evaluate the effectiveness of treatment [36]. This includes the choice of drug [37], type of therapy [38], and quality of surgical interventions [39]. That is why the specific detection of exosomes and potential control of their levels in biological fluids could provide a successful therapeutic strategy [40], including reducing their number to normal levels to prevent disease progression [41].

(ii) Biorecognition elements for exosomes, such as antibodies [42], aptamers [43], peptides [44], molecularly imprinted polymers [45], and and DARPins [46], bind to surface markers (e.g., cluster of differentiation 9 (CD9) protein [47], CD63 [48], CD81 [49]) or internal biomarkers (e.g., miRNAs [50], proteins [51]), enabling targeted isolation [52], detection [53], and characterization [54]. Basic conventional methods for separating exosomes comprise ultracentrifugation-based separation [55], immunological separation [56], ultrafiltration separation [57], size-exclusion chromatography [58], and polymer-based precipitation separation [59]. Despite the successes achieved in the separation of exosomes, significant difficulties remain due to the complexity of their structure. Widely used detection techniques include scanning electron microscopy (SEM) [60], atomic force microscopy (AFM) [61], nanoparticle tracking analysis (NTA) [62], dynamic light scattering (DLS) [63], transmission electron microscopy (TEM) [64], flow cytometry [65], western blotting (WB) [66], enzyme-linked immunosorbent assay (ELISA) [67], and Raman & surface-enhanced Raman spectroscopy (SERS) [68]. Each detection technique offers unique pros and cons, making it relevant

to combine with others for the creation of more advanced approaches for real-time, highly sensitive detection of selected exosomal markers using microliter volumes of samples [69]. Therefore, the challenges in exosome detection involve distinguishing their origin and accurately selecting targets on their surface. Currently, there is no single best detection protocol recognized, and it is required a sufficient number of clinical samples to evaluate the stability, accuracy, and specificity of each detection method [70]. Thus, there has been increasing interest in alternative methods that do not require labeling, as they promise to provide highly sensitive detection of novel biomarkers in oncology such as exosomes [71].

(iii-iv) One of the promising directions for future development in this field is developing of a lab-on-a-chip (LOC) that utilizes a label-free detection technique [72]. Label-free biosensors based on photonics allow for the detection of analytes through changes in the optical signal [73]. Currently, there is a significant amount of work being done to develop various types of optical biosensors that do not require labeling [74]. These biosensors are based on different principles of interaction of light with matter, such as transmission [75], emission [76], adsorption [77], and light scattering [78]. Based on these principles, some of the most commonly used techniques include the resonant wavelength shift (RWS) [79], the resonant angle change (RAC) [80], localized surface plasmon resonance (LSPR) [81], and the refractive index change (RIC) [82]. The presented methods, taken individually or in combination, can serve as highly sensitive detectors in the LOC platform. For instance, biosensors based on LSPRs have received attention for use in nanoplasmonic EV sensing due to their exceptional sensitivity to minute changes in the refractive index of the surrounding medium [83]. Bathini et al. demonstrated the use of self-assembled gold nanoislands for analyzing EVs purified from a breast cancer cell line and numerically showed that each square micrometer of the gold nanostructure on the sensor platform could accommodate 27 EVs [84]. However, in order to work effectively with individual sensors from the array on the platform and transport the necessary analytes and components for modifying sensitive elements, it is necessary to combine them with microfluidic devices [85].

The cross-sensitivity issue can be overcome by properly designing and fabricating of highly sensitive biosensors based on PICs and microfluidics. This is due to the low cost, short analysis time, small sample and reagent volume required, and the needed selectivity, specificity, and limit of detection (LOD) without the need for fluorescent labeling [86]. Among the various platforms for developing biosensors based on PICs, a silicon nitride (SixNy) and in particular a stoichiometric SiN (Si3N4) platforms stand out as a promising option due to its low optical loss, fabrication flexibility, and transparency in the visible (VIS) and near-infrared (NIR) regions [87]. For this reason, several promising works have been presented regarding detecting various analytes using PICs based on the Si3N4 platform for different diseases [88]. Grosman et al. demonstrated the detection of RNA fragments at concentrations of 10 cp/pL with a sensitivity of 750 nm/RIU. However, this sensor did not include a microfluidic system for precisely controlling analytes and modifying the active sensor surface in .situ. In another study, a microfluidic sensor was developed based on a SiN platform with a low LOD (2.6 x 10-6 RIU) for protein immobilization on different microring resonators (MRRs) in an array [89]. However, using a single cuvette for all the PICs on

the chip limits the ability to test them individually.

The dissertation goal. The goal of this dissertation is to create optical sensors for liquid analysis based on a combination of photonic integrated circuits and microfluidic devices.

To achieve this goal, the following problems were addressed:

1. To develop a design and a technological route of PICs based on Si3N4 platform combined with microfluidic devices, utilizing coupled analytical and numerical models to enhance sensor performance;

2. To characterize the developed hybrid nanophotonic-microfluidic sensor platform and evaluate the advantages and disadvantages of the sensors in terms of sensitivity, limit of detection, and sensing area constrained by the microfluidic channel;

3. To investigate the limitations of the hybrid nanophotonic-microfluidic sensors, focusing on optical coupling efficiency, propagation losses, temperature fluctuations (in both medium and analyte), flow rate stability, robustness, heating contact effects, and spectral resolution;

4. To investigate the potential of a highly developed nanophotonic-microfluidic sensor for LOC analysis of complex refractive indices of liquids;

5. To investigate the feasibility of a developed hybrid nanophotonic-microfluidic sensor based on Si3N4 platform for in-situ monitoring of layer-by-layer and conventional assemblies for surface modification, with regard to stability after washing, quantity, and thickness of the deposited layers;

6. To provide and study real-time functionalization capabilities of the sensitive nanophotonic sensors for the detection and quantification of biological markers, such as exosomes containing the specific membrane protein HER2.

Scientific novelty:

1. The extraction of complex RI from liquid analytes under flow conditions was successfully demonstrated by systematically varying the microfluidic channel width atop an MRR sensor.

2. The developed speckle demultiplexer, when integrated with microfluidic channels, demonstrates linear sensitivity for liquid analytes in single-channel detection mode.

3. Monolayer film detection and subsequent assembly processes were achieved using developed MRR and Mach-Zehnder interferometer (MZI) sensors on a silicon nitride platform integrated with microfluidic channels, employing the layer-by-layer assembly technique (LbL).

4. An all-optical surface functionalization of MZI-based photonic sensors integrated with microfluidic channels was achieved using designed ankyrin repeat proteins (DARPins), enabling label-free and specific detection of human epidermal growth factor receptor 2 (HER2) exosomes.

Theoretical and practical significance. The theoretical significance of the results lies, on the one hand, in gaining new knowledge about the interaction between the near-field waveguide mode ('evanescent mode') at the sensitive area of PICs and various biomarkers/liquids in the telecommunication wavelength range (1.3.6 - Optics). On the other hand, the study reveals the potential of a sensitive negatively charged Si3N4 surface regarding its ability to interact with dispersed and low-dimensional systems, enhancing immobilization through van der Waals forces, hydrogen, and covalent bonding of functional layers (1.3.8 - Physics of condensed matter).

The practical significance of the results includes new insights into developing optical sensor devices based on PICs and microfluidics, sensor surface modification, refractometric capabilities, and specific exosomes detection. These advancements will significantly contribute to implementing the strategic priority of the Russian Federation's scientific and technological development: transitioning to personalized, predictive, and preventive medicine, high-tech healthcare, and health-saving technologies. Furthermore, the results represent a crucial first step toward creating a LOC system for real-time, precise monitoring of coating applications, chemical analysis, and medical diagnostics or treatment effectiveness evaluation. The proposed approach will enable highly sensitive and rapid testing for viral and oncological diseases in clinical settings, substantially reducing both time and material costs for patient diagnostics.

The dissertation work was carried out with the support of the following scientific foundations:

• The Russian Science Foundation (RSF) under grants No. 19-72-10156 (PIC fabrication), No. 21-72-10117 (PIC testing), No. 22-14-00209 (Preparation of the microfluidic part of the sensor), No. 22-12-00351 (Numerical calculations), and No. 23-79-00056 (Design development), No. 23-13-00035 (PIC surface modification, EV sample preparation and characterization).

• The Russian Foundation for Basic Research under grant No. 18-29-27031 (Theoretical study).

• The Ministry of Science and Higher Education of the Russian Federation (FSME-2022-0008 and FSME-2025-0002) (experimental study).

• The Gennadiy Komissarov Foundation (scholarship) and Ministry of Science and Higher Education of the Russian Federation (Scholarship of the President of the Russian Federation, and Scholarships of the President of the Russian Federation for studying abroad 2022, 2024) (financial support and academic internships).

Methodology and research methods. The current dissertation is based on a combination of theoretical analysis (investigation of the limitations of the Kramers-Kronig relation, development of an approach for extracting the complex refractive index and sensitivity enhancement), mathematical modeling (investigation of sensitivity, LOD, and performance limitations of the developed platform; optimization of the geometry of PICs combined with microfluidic channels was performed in COMSOL Multiphysics®), and experimental methods (investigation of sensitivity, LOD, and performance limitations of the developed sensor platform was conducted using SEM, AFM, NTA, and WB).

Main results submitted for the defense:

1. A nanophotonic-microfluidic refractometer has been developed based on a silicon nitride platform. This device combines photonic ring microresonators with microfluidic channels to measure the complex refractive index of liquids within the range of 1480 - 1640 nm. It was found that as the degree of microfluidic channel coverage on the resonator increased from 25 % to 100 %, sensitivity and the detection limit both increased by a factor of three, to values of 132 nm/RIU and 7.2 x 10-6 RIU for the real part of the refractive index, respectively. (1.3.6 -Optics, directions of research: 3, 7).

2. A speckle demultiplexer based on a silicon nitride platform with a radius of 150 microns, a hole diameter of 150 nm, and a hole count of 11,450 has been developed, in which diffusion operating

conditions are achieved in 8 of the 11 output channels. When operating in the diffusion mode in combination with microfluidic channels, a linear sensitivity of 61.8 ± 2.3 nm/RIU was achieved for isopropanol concentrations in water ranging from 80 to 10-5 ppm. (1.3.6 - Optics, directions of research: 1,5).

3. A nanophotonic-microfluidic sensor has been developed based on a silicon nitride platform, which allows for in-situ monitoring of the formation of single monolayer and multilayer coatings formed by layer-by-layer assembly method. The sensitivity of this sensor, based on a Mach-Zehnder interferometer, was found to be 25 % higher than that of a sensor based on a micro-ring resonator, for detecting a layer of bovine serum albumin with a thickness of 8 ± 1 nm. The sensitivity of the Mach-Zehnder interferometer-based sensor for the same analyte (BSA) is 9 times greater than the results obtained from a previously developed refractometer based on microstructured fibers. (1.3.8 - Physics of condensed matter, directions of research: 4, 6).

4. A nanophotonic-microfluidic sensor based on the Mach-Zehnder interferometer has been developed, which allows in situ monitoring of the process of sensor surface modification by molecules of designed ankyrin repeat proteins necessary to increase the specificity of this device for exosomal tissue markers with increased expression of the HER2 receptor. An increase in the resonance wavelength shift of the interferometer by 250 pm was demonstrated for exosomes isolated from cell lines with the higher expression of the HER2 receptor, compared with the peak position for exosomes isolated from a cell line with the low expression of the HER2 receptor at the same concentration of the two types of exosomes studied ( 4.2 x 1010 mL-1). (1.3.8 - Physics of condensed matter, the direction of research: 2).

Validity of the obtained results. The reliability and validity of the obtained results are ensured through the application of advanced research methods, including AFM for surface characterization, NTA for exosome size and concentration measurements, SEM for high-resolution imaging of nanostructures, and WB for protein analysis and verification. These methods were carefully selected to provide comprehensive and accurate data, ensuring the reproducibility of the findings. Furthermore, the key results of the dissertation have been published in high-impact, peer-reviewed scientific journals, confirming their scientific significance and adherence to international research quality standards. The independent expert evaluation during the peer review process underscores the credibility and contribution of this work to the field of study.

Approbation of the dissertation work. The results of this work were regularly discussed at scientific seminars hosted by leading research groups in the dissertation's field of study, including:

• Laboratory of Photonic Gas Sensors at MISIS Universit (https://misis.ru/university/struktura-universiteta/lab/118/);

• BioPhotonics Lab at Skoltech (http://biophotonicsskoltech.ru/);

• Nanomembrane Group at Fudan University (https://nanomem.fudan.edu.cn/).

Besides, the main results of the work were presented at research schools, and national and international conferences, including:

1. Kuzin A.Yu., Chernyshev V.S., Florya I.N., Kovalyuk V.V., Golikov A.D., Goltsman G.G., Gorin D.A., "Photonic integrated circuits liquid/gas biopsy sensors for biomedical applications," XXI International Conference on Holography and Applied Optical Technologies (HOLOEXPO), Kazan, Russia, 09.09.2024-13.09.2024 (Oral presentation);

2. Kuzin A.Yu., Chernyshev V.S., Florya I.N., An P.P., Golikov A.D., Kovalyuk V.V., Goltsman G.G., Gorin D.A., "Optofluidic chip for CD63+/HER2+ extracellular vesicle quantification and breast cancer screening," Forum-exhibition HEALTHCARE-SKFO 2024, Pyatigorsk, Russia, 06.06.2024-08.06.2024 (Oral presentation);

3. Kuzin A.Yu., Chernyshev V.S., Florya I.N., An P.P., Golikov A.D., Kovalyuk V.V., Goltsman G.G., Gorin D.A., "Development of highly sensitive sensors based on a combination of photonic integrated circuits and microfluidic channels for biomedical applications," The 2nd Annual Russian Youth Conference "Methods and instruments for the analysis of biological samples "AnalitBioPribor-2023, St. Petersburg, Russia, 23.11.2023-24.11.2023 (Oral presentation);

4. Kuzin A.Yu., Chernyshev V.S., Kovalyuk V.V., An P.P., Golikov A.D., Svyatodukh S.S., Perevoschikov S., Deyev S.M, Florya I.N., Goltsman G.G., Gorin D.A., "Microfluidic integrated-optical lab-on-a-chip for disease diagnosis and treatment monitoring," The 2nd Annual Russian Youth Conference "Methods and instruments for the analysis of biological samples "AnalitBioPribor-2023, St. Petersburg, Russia, 23.11.2023-24.11.2023 (Oral presentation);

5. Kuzin A.Yu., Chernyshev V.S., Kovalyuk V.V., An P.P., Golikov A.D., Goltsman G.G., Gorin D.A., "In Situ Monitoring of Layer-By-Layer Assembly Surface Modification of Nanophotonic-Microfluidic," The 2nd BRICS Workshop on Biophotonics, Saratov, Russia, 16.05.2023-18.05.2023 (Oral presentation);

6. Kuzin A.Yu., Chernyshev V.S., Kovalyuk V.V., An P.P., Golikov A.D., Goltsman G.G., Gorin D.A., "Hybrid nanophotonic-microfluidic sensor for highlysensitive liquids and gases analyses," The 26nd Annual Conference Saratov Fall Meeting 2022 X Symposium on Optics & Biophotonics, Saratov, Russia, 26.09.2022-30.09.2022 (Oral presentation);

7. Kuzin A.Yu., Chernyshev V.S., Kovalyuk V.V., An P.P., Golikov A.D., Goltsman G.G., Gorin D.A., "Combination of photonic integrated circuits and microfluidic channels for highly sensitive applications in biomedical applications," 90 Years of Ufa State Aviation Technical University in Service to Science, Education, and Business, Ufa, Russia, 21.11.2022-22.11.2022 (Oral presentation);

8. Kuzin A.Yu., Lyubchak A.N., Golikov A.D., An P.P., Kovalyuk V.V., Goltsman G.G., "Thermo-optical effect in a Mach-Zehnder interferometer on a silicon nitride platform for quantum photonic applications," Saint Petersburg OPEN 2022, St. Petersburg, Russia, 24.05.2022-27.05.2022 (Poster);

9. Kuzin A.Yu., Elmanov, I. A., Elmanova, A. V., An, P. P., Kovalyuk, V. V., Goltsman, G. N., "On-chip Photonic Crystal Cavity Integrated with Thermal Graphene Source," The 43rd Symposium on Photonics and Electromagnetic Research (Photonics and Electromagnetic Research Symposium, PIERS 2021), Hangzhou, China, 25.04.2021-29.04.2021 (Oral presentation).

Publications. The main results on the topic of the dissertation were published in 5 papers in peer-reviewed scientific journals indexed in Web of Science and Scopus, 3 of which are included in the Nature Index.

Personal contribution of the author. The content of the dissertation and the main points presented for defense reflect the author's personal contribution to the published works, which were carried out by the author independently or in collaboration with colleagues.

The fabrication route for a hybrid nanophotonic-microfluidic sensor on a silicon nitride platform was developed in collaboration with Dr. Vadim Kovalyuk (NUST MISIS, MSPU, Russia), Dr. Vasiliy Chernyshev (V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Russia), and Alexander Golikov (MSPU, Russia).

The PIC characterization methodology and measurement setup were developed in collaboration with Dr. Vadim Kovalyuk (NUST MISIS, MSPU, Russia) and Pavel An (MSPU, Russia).

The methodology and setup for integrating photonic and microfluidic chips were developed in collaboration with Dr. Vasiliy Chernyshev (V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Russia).

The on-chip robust speckle demultiplexer integrated with microfluidics was developed and characterized in collaboration with Dr. Ilia Fradkin (Skoltech, Russia), Dr. Vasiliy Chernyshev (V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Russia), and Dr. Vadim Kovalyuk (NUST MISIS, MSPU, Russia).

The performance limitations of the developed nanophotonic-microfluidic sensor platform were characterized in collaboration with Dr. Vadim Kovalyuk (MISIS, MSPU, Russia), Dr. Vasiliy Chernyshev (V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Russia), Dr. Roman Ozhegov (HSE MIEM, MSPU, Russia), Pavel An (MSPU, Russia), and Irina Florya (NUST MISIS, MSPU, Russia).

The nanophotonic-microfluidic sensor for on-chip analysis of complex refractive index was developed and characterized in collaboration with Krupamaya Panda (EC Lyon, France and USYD, Australia), Irina Florya (NUST MISIS, MSPU, Russia), Dr. Vadim Kovalyuk (NUST MISIS, MSPU, Russia), Dr. Vasiliy Chernyshev (V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Russia).

In situ monitoring of LbL assembly for surface modification and functionalization of a nanophotonic-microfluidic sensor for specific exosomal marker detection was performed in collaboration with Dr. Vasiliy Chernyshev (V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Russia), Dr. Vadim Kovalyuk (NUST MISIS, MSPU, Russia).

The author's contribution included the formulation of tasks, analytical and numerical calculations to improve the performance of PICs, the selection of the most suitable PIC configurations based on their sensitivity, LOD, and robustness, developing of the photonic chip design, the integration of the photonic and microfluidic chips, conducting experiments and measuring the spectral characteristics of the developed sensors, characterizing the developed sensor platform,

processing the experimental results, participating in the discussion and analysis of the obtained data, as well as preparing scientific articles. All results presented for defense were obtained by the author personally or with his direct participation.

Dissertation structure. The dissertation consists of an introduction, 5 chapters, and a conclusion. The dissertation is 177 pages long, including 66 figures and 13 tables. The list of references contains 365 titles.

Заключение диссертации по теме «Другие cпециальности», Кузин Алексей Юрьевич

Conclusions

In the course of the dissertation work, all the set tasks were completed and the following scientific results were obtained:

• The design and fabrication route for hybrid nanophotonic-microfluidic sensors were developed. Sensors based on the Si3N4 platform incorporating PIC designs (MRR, MZI, and speckle demultiplexer) were successfully fabricated and integrated with microfluidic devices;

• The developed hybrid nanophotonic-microfluidic sensor platform based on PICs performed in MRR, MZI, and speckle demultiplexer configurations was characterized from 1480 to 1620 nm. The sensitivity and limit of detection depend on the geometry configuration of the developed PICs, and the area of coverage with microfluidic channels was investigated using different concentrations of isopropanol in deionized water as an analyte. For developed sensor configurations at a fixed microfluidic channel width of 100 pm, the best sensitivity values (LOD) for MRRs, MZI, and speckle demultiplexer were 138.2 nm/RIU (11 ppm), 96.2 nm/RIU (180 ppm), and 61.8 nm/RIU (290 ppm), respectively. At the same time, the speckle demultiplexer demonstrated enhanced robustness and a sensing area 150 times larger than comparable MZI and MRR configurations;

• The performance limitations of the developed nanophotonic-microfluidic sensor platform were systematically investigated, including optical coupling efficiency, propagation losses, temperature fluctuations in the medium and analyte, flow rate control stability, thermal influence of heating contacts, and spectral resolution;

• A nanophotonic-microfluidic refractometer has been developed on a silicon nitride platform, based on a combination of photonic MRRs with microfluidic channels, enabling precise measurement of the complex refractive index of liquids pushed across. The maximum relative deviation between extracted and literature data for deionized water in the case of real and imaginary parts of refractive index were 0.44% and 37%, correspondingly;

• A method for controlling the surface modification of photonic integrated sensors based on Si3N4 was developed, utilizing convective and layer-by-layer assembly techniques. The sensitivity of the developed sensor, based on a MZI, was found to be 25 % higher than that of a sensor based on a micro-ring resonator, for detecting a layer of bovine serum albumin with a thickness of 8 ± 1 nm;

• A nanophotonic-microfluidic sensor based on a MZI has been developed, enabling in situ monitoring of sensor surface modification. This modification involves the attachment of designed ankyrin repeat proteins, which enhance the device's specificity for detecting exosomal tissue markers with elevated expression of the human epidermal growth factor receptor 2.

Based on this, a real-time protocol was established to monitor the modification of SisN4 surfaces for receptor activation, using small extracellular vesicles containing the specific membrane protein as the analyte.

As a result, the goal of the dissertation work has been achieved: optical sensors for liquid analysis based on a combination of photonic integrated circuits and microfluidic devices were developed and comprehensively studied.

The results of this dissertation work demonstrate that the developed sensor platform, based on a combination of PICs and MFCs, has several advantages. These include the ability to analyze very small volumes of analyte, scalability, reusability, high sensitivity, a low LOD, specificity, and real-time scanning capabilities. As a result, numerous applications become available for further development of this platform (Figure 66). For example, as already demonstrated, integrating the developed platform with machine learning enables advanced real-time state-of-charge monitoring in vanadium redox flow batteries [334]. Besides, through a microfluidic assembly of silica colloidal particles, specific sensing of gases and vapors can be achieved in the developed nanophotonic-microfluidic platform for gas biopsy and environmental applications [365]. Therefore, the significant advances in packaged lab prototypes bring the technology closer to real-world applications. A key goal is replacing bulky, time-consuming clinical tests with high-performance silicon nitride-based label-free LOC systems. Another promising direction is the development of a portable biosensor system that can be controlled using smartphones for routine biological assays, enabling future POC diagnostics.

Figure 66 — Promising applications of the developed optical sensors for liquid analysis based on a combination of PICs and MFCs.

In addition, future research directions that could emerge from this work and have the potential to advance the field, could begin with the following steps:

• In this work, a rib waveguide design supporting TE single-mode propagation was implemented for Rl-based MRR and MZI sensors (Sections 3.3 and 3.2). Despite the successful results achieved, further optimization of waveguide-based sensor designs can enhance their sensitivity. The following simple yet effective design strategies can be employed: (i) utilizing TM-polarized optical modes with strong evanescent fields near the top surface, (ii) incorporating slotted segments in the sensing region, (iii) implementing ultra-thin waveguide structures, (iv) developing suspended sensing structures to enhance evanescent field-analyte interaction, and (v) employing porous silicon waveguides to increase the active sensing area.

• The results presented for the speckle demultiplexer demonstrate the potential of the device for detecting RI changes with high robustness, although the potential error remains relatively large (Section 3.4). However, the precision could be significantly improved by employing more advanced data processing techniques and, crucially, by incorporating spectra from all output channels. It will allow to use the speckle demultiplexer not only for optical density measurements, but also for direct spectral reconstruction and chemical composition analysis, with the help of appropriate data processing algorithms.

• The important outcome of this dissertation work is the development of an algorithm for in situ monitoring of surface functionalization via DARPin attachment, enhancing the specificity of the nanophotonic-microfluidic sensor for detecting exosomal tissue markers with elevated HER2 expression (Section 5.3). However, further steps include modifying the protocol for surface functionalization to validate specific exosomal markers or proteins for RI-based MRR and MZI sensors. Additionally, it will be necessary to investigate the S and LOD of specific HER2-based proteins and exosomes to compare them with ELISA or other methods.

Список литературы диссертационного исследования кандидат наук Кузин Алексей Юрьевич, 2025 год

Bibliography

1. Nayak S., Blumenfeld N. R., Laksanasopin T., and Sia S. K. Point-of-care diagnostics: recent developments in a connected age // Analytical chemistry. — 2017. — Vol. 89, no. 1.— P. 102-123.

2. Chin C. D., Linder V., and Sia S. K. Commercialization of microfluidic point-of-care diagnostic devices // Lab on a Chip.— 2012.— Vol. 12, no. 12. —P. 2118-2134.

3. Bray F., Laversanne M., Sung H., Ferlay J., Siegel R. L., Soerjomataram I., and Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries // CA: a cancer journal for clinicians. — 2024. — Vol. 74, no. 3. —P. 229-263.

4. Wild C., Weiderpass E., and Stewart B. World cancer report : International Agency for Research on Cancer. — 2020. — Access mode: https://www.ncbi.nlm.nih.gov/books/ NBK606505/ (online; accessed: 2024-07-20).

5. Loud J. T. and Murphy J. Cancer screening and early detection in the 21st century // Seminars in oncology nursing / Elsevier. — 2017.—Vol. 33.—P. 121-128.

6. Shah S. C., Kayamba V., Peek Jr R. M., and Heimburger D. Cancer control in low-and middle-income countries: is it time to consider screening? // Journal of global oncology. — 2019.—Vol. 5. —P. 1-8.

7. Assessing national capacity for the prevention and control of noncommunicable diseases: report of the 2021 global survey / World Health Organization. — 2023. — ISBN: 9789240071698. — Access mode: https://www.who.int/publications/i/item/ 9789240002319 (online; accessed: 2024-07-10).

8. Crosby D., Bhatia S., Brindle K. M., Coussens L. M., Dive C., Emberton M., Esener S., Fitzgerald R. C., Gambhir S. S., Kuhn P., et al. Early detection of cancer // Science.— 2022.—Vol. 375, no. 6586. —P. eaay9040.

9. Siravegna G., Marsoni S., Siena S., and Bardelli A. Integrating liquid biopsies into the management of cancer // Nature reviews Clinical oncology. — 2017.—Vol. 14, no. 9.— P. 531-548.

10. Lone S. N., Nisar S., Masoodi T., Singh M., Rizwan A., Hashem S., El-Rifai W., Bedognetti D., Batra S. K., Haris M., et al. Liquid biopsy: a step closer to transform diagnosis, prognosis and future of cancer treatments // Molecular cancer. — 2022. — Vol. 21, no. 1. — P. 79.

11. Kok R., van Schaijik B., Johnson N. W., Malki M. I., Frydrych A., and Kujan O. Breath biopsy, a novel technology to identify head and neck squamous cell carcinoma: A systematic review // Oral Diseases.— 2023.— Vol. 29, no. 8. —P. 3034-3048.

12. Chaturvedi V. K., Singh A., Singh V. K., and Singh M. P. Cancer nanotechnology: a new revolution for cancer diagnosis and therapy // Current drug metabolism. — 2019. — Vol. 20, no. 6. —P. 416-429.

13.

14.

15.

16.

17.

18.

19.

20.

21

22

23

24

25

26

Chen H., Wang L., Zeng X., Schwarz H., Nanda H. S., Peng X., and Zhou Y. Exosomes, a new star for targeted delivery // Frontiers in Cell and Developmental Biology. — 2021. — Vol. 9. —P. 751079.

Chargaff E. and West R. THE BIOLOGICAL SIGNIFICANCE OF THE THROMBOPLAS-TIC PROTEIN OF BLOOD // Journal of Biological Chemistry. — 1946. — Vol. 166, no. 1. — P. 189-197.

Tkach M. and Thery C. Communication by extracellular vesicles: where we are and where we need to go // Cell.— 2016.— Vol. 164, no. 6. —P. 1226-1232.

Tenchov R., Sasso J. M., Wang X., Liaw W.-S., Chen C.-A., and Zhou Q. A. Exosomes-nature's lipid nanoparticles, a rising star in drug delivery and diagnostics // ACS nano. — 2022.—Vol. 16, no. 11. —P. 17802-17846.

Kalluri R. and LeBleu V. S. The biology, function, and biomedical applications of exosomes // science. — 2020. — Vol. 367, no. 6478. — P. eaau6977.

Chuo S. T.-Y., Chien J. C.-Y., and Lai C. P.-K. Imaging extracellular vesicles: current and emerging methods // Journal of biomedical science. — 2018.—Vol. 25.—P. 1-10.

Chernyshev V. S., Chuprov-Netochin R. N., Tsydenzhapova E., Van Devener B., Leonov S., Gorin D., and Skliar M. Dynamic surface tension probe for measuring the concentration of extracellular vesicles // Biochemical and Biophysical Research Communications. — 2022. — Vol. 609. —P. 189-194.

Mitri Z., Constantine T., and O Regan R. The HER2 receptor in breast cancer: pathophysi-ology, clinical use, and new advances in therapy // Chemotherapy research and practice. — 2012.—Vol. 2012, no. 1. —P. 743193.

Sabapatha A., Gercel-Taylor C., and Taylor D. D. Specific isolation of placenta-derived exosomes from the circulation of pregnant women and their immunoregulatory consequences 1 // American Journal of Reproductive Immunology. — 2006.—Vol. 56, no. 5-6. — P. 345355.

Gurunathan S., Kang M.-H., Jeyaraj M., Qasim M., and Kim J.-H. Review of the isolation, characterization, biological function, and multifarious therapeutic approaches of exosomes // Cells. —2019.—Vol. 8, no. 4. —P. 307.

Simpson R. J., Jensen S. S., and Lim J. W. Proteomic profiling of exosomes: current perspectives // Proteomics. — 2008.—Vol. 8, no. 19. —P. 4083-4099.

Caby M.-P., Lankar D., Vincendeau-Scherrer C., Raposo G., and Bonnerot C. Exosomal-like vesicles are present in human blood plasma // International immunology. — 2005. — Vol. 17, no. 7. —P. 879-887.

Pisitkun T., Shen R.-F., and Knepper M. A. Identification and proteomic profiling of exosomes in human urine // Proceedings of the National Academy of Sciences. — 2004. —Vol. 101, no. 36. —P. 13368-13373.

Saman S., Kim W., Raya M., Visnick Y., Miro S., Saman S., Jackson B., McKee A. C., Alvarez V. E., Lee N. C., et al. Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease // Journal of biological chemistry. —2012.—Vol. 287, no. 6.—P. 3842-3849.

27. Keller S., Rupp C., Stoeck A., Runz S., Fogel M., Lugert S., Hager H.-D., Abdel-Bakky M., Gutwein P., and Altevogt P. CD24 is a marker of exosomes secreted into urine and amniotic fluid // Kidney international. — 2007.— Vol. 72, no. 9.—P. 1095-1102.

28. Admyre C., Grunewald J., Thyberg J., Gripenback S., Tornling G., Eklund A., Scheynius A., and Gabrielsson S. Exosomes with major histocompatibility complex class II and co-stimulatory molecules are present in human BAL fluid // European Respiratory Journal. — 2003.—Vol. 22, no. 4. —P. 578-583.

29. Skriner K., Adolph K., Jungblut P. R., and Burmester G. R. Association of citrullinated proteins with synovial exosomes // Arthritis & Rheumatism: Official Journal of the American College of Rheumatology. —2006. —Vol. 54, no. 12.—P. 3809-3814.

30. Admyre C., Johansson S. M., Qazi K. R., Filen J.-J., Lahesmaa R., Norman M., Neve E. P., Scheynius A., and Gabrielsson S. Exosomes with immune modulatory features are present in human breast milk // The Journal of immunology. — 2007. — Vol. 179, no. 3. — P. 1969-1978.

31. Kowalczyk A., Wrzecinska M., Czerniawska-Pikatkowska E., and Kupczynski R. Exosomes-Spectacular role in reproduction // Biomedicine & Pharmacotherapy. — 2022. — Vol. 148.— P. 112752.

32. Grigor'eva A. E., Tamkovich S. N., Eremina A. V., Tupikin A. E., Kabilov M. R., Chernykh V. V., Vlassov V. V., Laktionov P. P., and Ryabchikova E. I. Exosomes in tears of healthy individuals: Isolation, identification, and characterization // Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry. — 2016.—Vol. 10, no. 2. — P. 165-172.

33. Liu J., Chen Y., Pei F., Zeng C., Yao Y., Liao W., and Zhao Z. Extracellular vesicles in liquid biopsies: potential for disease diagnosis // BioMed Research International. — 2021.— Vol. 2021, no. 1. —P. 6611244.

34. El Andaloussi S., Mager I., Breakefield X. O., and Wood M. J. Extracellular vesicles: biology and emerging therapeutic opportunities // Nature reviews Drug discovery. — 2013. —Vol. 12, no. 5. —P. 347-357.

35. Tutrone R., Donovan M. J., Torkler P., Tadigotla V., McLain T., Noerholm M., Skog J., and McKiernan J. Clinical utility of the exosome based ExoDx Prostate (IntelliScore) EPI test in men presenting for initial Biopsy with a PSA 2-10 ng/mL // Prostate Cancer and Prostatic Diseases. —2020.—Vol. 23, no. 4. —P. 607-614.

36. Hazrati A., Mirsanei Z., Heidari N., Malekpour K., Rahmani-Kukia N., Abbasi A., and Soudi S. The potential application of encapsulated exosomes: A new approach to increase exosomes therapeutic efficacy // Biomedicine & Pharmacotherapy. — 2023.—Vol. 162.— P. 114615.

37. Rezaie J., Feghhi M., and Etemadi T. A review on exosomes application in clinical trials: perspective, questions, and challenges // Cell Communication and Signaling. — 2022. — Vol. 20, no. 1. —P. 145.

38. Zhang M., Hu S., Liu L., Dang P., Liu Y., Sun Z., Qiao B., and Wang C. Engineered exosomes from different sources for cancer-targeted therapy // Signal transduction and targeted therapy. — 2023.—Vol. 8, no. 1.—P. 124.

39. Pinto H. and Sánchez-Vizcaíno Mengual E. Exosomes in the real world of medical aesthetics: A review // Aesthetic Plastic Surgery.— 2024.— Vol. 48, no. 13. —P. 2513-2527.

40

41

42

43

44

45

46

47

48

49

50

51

52

53

Thery C., Ostrowski M., and Segura E. Membrane vesicles as conveyors of immune responses // Nature reviews immunology. — 2009. — Vol. 9, no. 8. — P. 581-593.

Wang J., Sun X., Zhao J., Yang Y., Cai X., Xu J., and Cao P. Exosomes: a novel strategy for treatment and prevention of diseases // Frontiers in pharmacology. — 2017.—Vol. 8.— P. 300.

Wang C., Jin D., Yu Y., Tang L., Sun Y., Sun Z., and Zhang G.-J. A dual antibody-modified nanochannel biosensor for capture and identification of exosomes // Sensors and Actuators B: Chemical. —2020.—Vol. 314. —P. 128056.

Zhu C., Li L., Wang Z., Irfan M., and Qu F. Recent advances of aptasensors for exosomes detection // Biosensors and Bioelectronics. — 2020.—Vol. 160. — P. 112213.

da Fonseca Alves R., Pallares-Rusinol A., Rossi R., Marti M., Vaz E. R., de Araujo T. G., Sotomayor M. D. P. T., and Pividori M. I. Peptide-based biosensing approaches for targeting breast cancer-derived exosomes // Biosensors and Bioelectronics. — 2024. — Vol. 255. — P. 116211.

Zhang J., Chen Q., Gao X., Lin Q., Suo Z., Wu D., Wu X., and Chen Q. A Label-Free and Antibody-Free Molecularly Imprinted Polymer-Based Impedimetric Sensor for NSCLC-Cells-Derived Exosomes Detection // Biosensors. — 2023. — Vol. 13, no. 6. — P. 647.

Yonet-Tanyeri N., Ahlmark B. Z., and Little S. R. Advances in Multiplexed Paper-Based Analytical Devices for Cancer Diagnosis: A Review of Technological Developments // Advanced materials technologies. — 2021.—Vol. 6, no. 8.—P. 2001138.

Mazurov D., Barbashova L., and Filatov A. Tetraspanin protein CD 9 interacts with metallo-protease CD 10 and enhances its release via exosomes // The FEBS journal. — 2013. —Vol. 280, no. 5.—P. 1200-1213.

Song Z., Mao J., Barrero R. A., Wang P., Zhang F., and Wang T. Development of a CD63 aptamer for efficient cancer immunochemistry and immunoaffinity-based exosome isolation // Molecules. —2020. —Vol. 25, no. 23. —P. 5585.

Fan Y., Pionneau C., Cocozza F., Boelle P.-y., Chardonnet S., Charrin S., Thery C., Zimmermann P., and Rubinstein E. Differential proteomics argues against a general role for CD9, CD81 or CD63 in the sorting of proteins into extracellular vesicles // Journal of Extracellular Vesicles. —2023.—Vol. 12, no. 8. —P. 12352.

Wu Y., Zhang Y., Zhang X., Luo S., Yan X., Qiu Y., Zheng L., and Li L. Research advances for exosomal miRNAs detection in biosensing: From the massive study to the individual study // Biosensors and Bioelectronics. — 2021.—Vol. 177. — P. 112962.

Chang K., Sun P., Dong X., Zhu C., Liu X., Zheng D., and Liu C. Aptamers as recognition elements for electrochemical detection of exosomes // Chemical Research in Chinese Universities. —2022. —Vol. 38, no. 4. —P. 879-885.

Gaillard M., Thuaire A., Nonglaton G., Agache V., Roupioz Y., and Raillon C. Biosensing extracellular vesicles: contribution of biomolecules in affinity-based methods for detection and isolation // Analyst. — 2020.— Vol. 145, no. 6.—P. 1997-2013.

Boriachek K., Masud M. K., Palma C., Phan H.-P., Yamauchi Y., Hossain M. S. A., Nguyen N.-T., Salomon C., and Shiddiky M. J. Avoiding pre-isolation step in exosome analysis: direct isolation and sensitive detection of exosomes using gold-loaded nanoporous ferric oxide nanozymes // Analytical chemistry. — 2019. — Vol. 91, no. 6. — P. 3827-3834.

54. Altintas O. and Saylan Y. Exploring the versatility of exosomes: a review on isolation, characterization, detection methods, and diverse applications // Analytical chemistry. — 2023.—Vol. 95, no. 44. —P. 16029-16048.

55. An M., Wu J., Zhu J., and Lubman D. M. Comparison of an optimized ultracentrifugation method versus size-exclusion chromatography for isolation of exosomes from human serum // Journal of proteome research. — 2018. — Vol. 17, no. 10. — P. 3599-3605.

56. Xu W.-M., Li A., Chen J.-J., and Sun E.-J. Research development on exosome separation technology // The Journal of membrane biology. — 2023. — Vol. 256, no. 1. — P. 25-34.

57. Chernyshev V. S., Chuprov-Netochin R. N., Tsydenzhapova E., Svirshchevskaya E. V., Poltavtseva R. A., Merdalimova A., Yashchenok A., Keshelava A., Sorokin K., Keshelava V., et al. Asymmetric depth-filtration: A versatile and scalable method for high-yield isolation of extracellular vesicles with low contamination // Journal of Extracellular Vesicles. — 2022. — Vol. 11, no. 8. —P. e12256.

58. Yu L.-L., Zhu J., Liu J.-X., Jiang F., Ni W.-K., Qu L.-S., Ni R.-Z., Lu C.-H., and Xiao M.-B. A comparison of traditional and novel methods for the separation of exosomes from human samples // BioMed research international. — 2018.—Vol. 2018, no. 1. — P. 3634563.

59. Gao M., Cai J., Zitkovsky H. S., Chen B., and Guo L. Comparison of yield, purity, and functional properties of large-volume exosome isolation using ultrafiltration and polymer-based precipitation // Plastic and Reconstructive Surgery. — 2022.—Vol. 149, no. 3.— P. 638-649.

60. Sokolova V., Ludwig A.-K., Hornung S., Rotan O., Horn P. A., Epple M., and Giebel B. Characterisation of exosomes derived from human cells by nanoparticle tracking analysis and scanning electron microscopy // Colloids and Surfaces B: Biointerfaces. — 2011. — Vol. 87, no. 1. —P. 146-150.

61. Sunkara V., Woo H.-K., and Cho Y.-K. Emerging techniques in the isolation and characterization of extracellular vesicles and their roles in cancer diagnostics and prognostics // Analyst. —2016. —Vol. 141, no. 2.—P. 371-381.

62. Dragovic R. A., Gardiner C., Brooks A. S., Tannetta D. S., Ferguson D. J., Hole P., Carr B., Redman C. W., Harris A. L., Dobson P. J., et al. Sizing and phenotyping of cellular vesicles using Nanoparticle Tracking Analysis // Nanomedicine: Nanotechnology, Biology and Medicine. —2011.—Vol. 7, no. 6. —P. 780-788.

63. Stetefeld J., McKenna S. A., and Patel T. R. Dynamic light scattering: a practical guide and applications in biomedical sciences // Biophysical reviews. — 2016.—Vol. 8. — P. 409-427.

64. Raposo G. and Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends // Journal of Cell Biology. — 2013. — Vol. 200, no. 4. — P. 373-383.

65. Zhang H., Freitas D., Kim H. S., Fabijanic K., Li Z., Chen H., Mark M. T., Molina H., Martin A. B., Bojmar L., et al. Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation // Nature cell biology. — 2018.—Vol. 20, no. 3. —P. 332-343.

66. Taylor D. D. and Gercel-Taylor C. RETRACTED: MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer // Gynecologic Oncology. — 2008. — Vol. 110, no. 1.—P. 13-21.

67

68

69

70

71

72

73

74

75

76

77

78

79

80

81

Liu C., Xu X., Li B., Situ B., Pan W., Hu Y., An T., Yao S., and Zheng L. Single-exosome-counting immunoassays for cancer diagnostics // Nano letters. — 2018. — Vol. 18, no. 7.— P. 4226-4232.

Koster H. J., Rojalin T., Powell A., Pham D., Mizenko R. R., Birkeland A. C., and Carney R. P. Surface enhanced Raman scattering of extracellular vesicles for cancer diagnostics despite isolation dependent lipoprotein contamination // Nanoscale. — 2021.—Vol. 13, no. 35.— P. 14760-14776.

Zhang M., Jin K., Gao L., Zhang Z., Li F., Zhou F., and Zhang L. Methods and technologies for exosome isolation and characterization // Small Methods. — 2018.—Vol. 2, no. 9.— P. 1800021.

Lin S., Yu Z., Chen D., Wang Z., Miao J., Li Q., Zhang D., Song J., and Cui D. Progress in microfluidics-based exosome separation and detection technologies for diagnostic applications // Small. —2020. —Vol. 16, no. 9.—P. 1903916.

Donzella V. and Crea F. Optical biosensors to analyze novel biomarkers in oncology // Journal of Biophotonics. — 2011.— Vol. 4, no. 6.—P. 442-452.

García-Meca C., Lechago S., Brimont A., Griol A., Mas S., Sanchez L., Bellieres L., Losilla N. S., and Martí J. On-chip wireless silicon photonics: from reconfigurable interconnects to lab-on-chip devices // Light: Science & Applications. — 2017.—Vol. 6, no. 9.— P. e17053-e17053.

Estevez M. C., Alvarez M., and Lechuga L. M. Integrated optical devices for lab-on-a-chip biosensing applications // Laser & Photonics Reviews. — 2012.—Vol. 6, no. 4. — P. 463-487.

Zanchetta G., Lanfranco R., Giavazzi F., Bellini T., and Buscaglia M. Emerging applications of label-free optical biosensors // Nanophotonics. — 2017.—Vol. 6, no. 4.—P. 627-645.

McBirney S. E., Chen D., Scholtz A., Ameri H., and Armani A. M. Rapid diagnostic for point-of-care malaria screening // ACS sensors. — 2018.—Vol. 3, no. 7. — P. 1264-1270.

Chen Y.-C. and Fan X. Biological lasers for biomedical applications // Advanced Optical Materials. —2019. —Vol. 7, no. 17. —P. 1900377.

Rodrigo D., Limaj O., Janner D., Etezadi D., García de Abajo F. J., Pruneri V., and Altug H. Mid-infrared plasmonic biosensing with graphene // Science. — 2015. —Vol. 349, no. 6244. — P. 165-168.

Krasnok A., Caldarola M., Bonod N., and Alú A. Spectroscopy and biosensing with optically resonant dielectric nanostructures // Advanced optical materials. — 2018. — Vol. 6, no. 5.— P. 1701094.

Washburn A. L., Gunn L. C., and Bailey R. C. Label-free quantitation of a cancer biomarker in complex media using silicon photonic microring resonators // Analytical chemistry. — 2009.—Vol. 81, no. 22. —P. 9499-9506.

Teramura Y. and Iwata H. Label-free immunosensing for a-fetoprotein in human plasma using surface plasmon resonance // Analytical biochemistry. — 2007.—Vol. 365, no. 2.— P. 201-207.

Chen S., Svedendahl M., Kall M., Gunnarsson L., and Dmitriev A. Ultrahigh sensitivity made simple: nanoplasmonic label-free biosensing with an extremelylow limit-of-detection for bacterial and cancer diagnostics // Nanotechnology. — 2009. — Vol. 20, no. 43. — P. 434015.

82

83

84

85

86

87

88

89

90

91

92

93

94

95

Gohring J. T., Dale P. S., and Fan X. Detection of HER2 breast cancer biomarker using the opto-fluidic ring resonator biosensor // Sensors and Actuators B: Chemical. — 2010. — Vol. 146, no. 1. —P. 226-230.

Amrollahi P., Zheng W., Monk C., Li C.-Z., and Hu T. Y. Nanoplasmonic sensor approaches for sensitive detection of disease-associated exosomes // ACS applied bio materials. — 2021. — Vol. 4, no. 9.—P. 6589-6603.

Bathini S., Raju D., Badilescu S., Kumar A., Ouellette R., Ghosh A., and Packirisamy M. Nano-bio interactions of extracellular vesicles with gold nanoislands for early cancer diagnosis // Research. —2018. —no. 3917986.

Dawson H., Elias J., Etienne P., and Calas-Etienne S. The rise of the OM-LoC: Opto-microfluidic enabled lab-on-Chip // Micromachines. — 2021.—Vol. 12, no. 12. — P. 1467.

Mai A., Mai C., and Steglich P. From Lab-on-chip to Lab-in-App: Challenges towards silicon photonic biosensors product developments // Results in Optics. — 2022. — Vol. 9.— P. 100317.

Huang Y., Song J., Luo X., Liow T.-Y., and Lo G.-Q. CMOS compatible monolithic multi-layer Si3N4-on-SOI platform for low-loss high performance silicon photonics dense integration // Optics Express. —2014.—Vol. 22, no. 18. —P. 21859-21865.

Grosman A., Duanis-Assaf T., Mazurski N., Zektzer R., Frydendahl C., Stern L., Reches M., and Levy U. On-chip multivariant COVID 19 photonic sensor based on silicon nitride double-microring resonators // Nanophotonics. — 2023.—Vol. 12, no. 14.—P. 2831-2839.

Besselink G., Heideman R., Schreuder E., Wevers L., Falke F., and Van den Vlekkert H. Performance of arrayed microring resonator sensors with the TriPleX platform // J. Biosens. Bioelectron. — 2016. — Vol. 7, no. 2. —P. 1000209.

Gorton L. Biosensors and modern biospecific analytical techniques. — 1st edition ed. — Elsevier, 2005. —Vol. 44. —P. 1-635.—ISBN: 0-444-50715-9.

Renaud J.-P., Chung C.-w., Danielson U. H., Egner U., Hennig M., Hubbard R. E., and Nar H. Biophysics in drug discovery: impact, challenges and opportunities // Nature reviews Drug discovery. —2016.—Vol. 15, no. 10.—P. 679-698.

Chalyan T., Potrich C., Schreuder E., Falke F., Pasquardini L., Pederzolli C., Heideman R., and Pavesi L. Afm1 detection in milk by fab'functionalized si3n4 asymmetric mach-zehnder interferometric biosensors // Toxins. — 2019. — Vol. 11, no. 7.—P. 409.

Ramirez J. C., Grajales Garcia D., Maldonado J., and Fernandez-Gavela A. Current Trends in Photonic Biosensors: Advances towards Multiplexed Integration // Chemosensors. — 2022.—Vol. 10, no. 10. —P. 398.

Ermatov T., Novoselova M., Skibina J., Machnev A., Gorin D., and Noskov R. E. Ultrasmooth, biocompatible, and removable nanocoating for hollow-core microstructured optical fibers // Opt. Lett. —2021. —Vol. 46, no. 19.—P. 4828-4831.

Virk J. K., Das S., Kaler R., Singh H., and Kundu T. D-shape optical fiber probe dimension optimization for LSPR based bio-sensor // Optical Fiber Technology. — 2022. — Vol. 71.— P. 102930.

96. Ding R., Chen Y., Wang Q., Wu Z., Zhang X., Li B., and Lin L. Recent advances in quantum dots-based biosensors for antibiotics detection // Journal of Pharmaceutical Analysis. — 2022.—Vol. 12, no. 3. —P. 355-364.

97. Han Y., Shchukin D., Schneider J., and Möhwald H. Fluorescence indicative pH drop in sonication // Colloids and Surfaces A: Physicochemical and Engineering Aspects. — 2014.— Vol. 445. —P. 30-33.

98. Azzouz A., Hejji L., Kim K.-H., Kukkar D., Souhail B., Bhardwaj N., Brown R. J., and Zhang W. Advances in surface plasmon resonance-based biosensor technologies for cancer biomarker detection // Biosensors and Bioelectronics. — 2022. — Vol. 197.—P. 113767.

99. Chen Y., Liu J., Yang Z., Wilkinson J. S., and Zhou X. Optical biosensors based on refractometric sensing schemes: A review // Biosensors and Bioelectronics. — 2019.—Vol. 144. —P. 111693.

100. Lechuga L. M. Optical biosensors // Comprehensive analytical chemistry. — 2005. — Vol. 44.—P. 209-250.

101. Li T.-D., Zhang R., Chen H., Huang Z.-P., Ye X., Wang H., Deng A.-M., and Kong J.-L. An ultrasensitive polydopamine bi-functionalized SERS immunoassay for exosome-based diagnosis and classification of pancreatic cancer // Chemical science. — 2018. — Vol. 9, no. 24. —P. 5372-5382.

102. Satyanarayana S., Karnik R. N., and Majumdar A. Stamp-and-stick room-temperature bonding technique for microdevices // Journal of Microelectromechanical Systems. — 2005. — Vol. 14, no. 2. —P. 392-399.

103. Densmore A., Xu D.-X., Janz S., Waldron P., Mischki T., Lopinski G., Deläge A., Lapointe J., Cheben P., Lamontagne B., and Schmid J. H. Spiral-path high-sensitivity silicon photonic wire molecular sensor with temperature-independent response // Optics Letters. — 2008. — Vol. 33, no. 6. —P. 596-598.

104. Bonnot K., Cuesta-Soto F., Rodrigo M., Varriale A., Sanchez N., D'Auria S., Spitzer D., and Lopez-Royo F. Biophotonic ring resonator for ultrasensitive detection of DMMP as a simulant for organophosphorus agents // Analytical Chemistry. — 2014. — Vol. 86, no. 10.— P. 5125-5130.

105. Grist S. M., Schmidt S. A., Flueckiger J., Donzella V., Shi W., Fard S. T., Kirk J. T., Ratner D. M., Cheung K. C., and Chrostowski L. Silicon photonic micro-disk resonators for label-free biosensing // Optics Express. — 2013.—Vol. 21, no. 7. — P. 7994-8006.

106. Wang Z., Zhang J., Xie J., Yin Y., Wang Z., Shen H., Li Y., Li J., Liang S., Cui L., Zhang H., and Yang B. Patterning organic/inorganic hybrid bragg stacks by integrating one-dimensional photonic crystals and macrocavities through photolithography: toward tunable colorful patterns as highly selective sensors // ACS Applied Materials & Interfaces. — 2012.—Vol. 4, no. 3.—P. 1397-1403.

107. Zinoviev K., Carrascosa L. G., Sanchez del Río J., Sepulveda B., Domínguez C., and Lechuga L. M. Silicon photonic biosensors for lab-on-a-chip applications // Advances in Optical Technologies. —2008.—Vol. 2008.—P. 1-6.

108. Shekhar S., Bogaerts W., Chrostowski L., Bowers J. E., Hochberg M., Soref R., and Shas-tri B. J. Roadmapping the next generation of silicon photonics // Nature Communications. — 2024.—Vol. 15, no. 1. —P. 751.

109. Soref R. and Lorenzo J. Single-crystal silicon: a new material for 1.3 and 1.6 ^m integrated-optical components // Electronics Letters. — 1985. — Vol. 21, no. 21. — P. 953-954.

110. Schmidtchen J., Splett A., Schuppert B., Petermann K., and Burbach G. Low loss singlemode optical waveguides with large cross-section in silicon-on-insulator // Electronics letters. — 1991. —Vol. 27, no. 16. —P. 1486-1488.

111. Bestwick T. ASOC/sup TM/-a silicon-based integrated optical manufacturing technology // 1998 Proceedings. 48th Electronic Components and Technology Conference (Cat. No. 98CH36206) / IEEE. —1998. —P. 566-571.

112. Liu A., Jones R., Liao L., Samara-Rubio D., Rubin D., Cohen O., Nicolaescu R., and Paniccia M. A high-speed silicon optical modulator based on a metal-oxide-semiconductor capacitor // Nature. — 2004.—Vol. 427, no. 6975. —P. 615-618.

113. Ahn D., Hong C.-y., Liu J., Giziewicz W., Beals M., Kimerling L. C., Michel J., Chen J., and Kartner F. X. High performance, waveguide integrated Ge photo detectors // Optics express. —2007. —Vol. 15, no. 7.—P. 3916-3921.

114. Fang A. W., Park H., Cohen O., Jones R., Paniccia M. J., and Bowers J. E. Electrically pumped hybrid AlGaInAs-silicon evanescent laser // Optics express. — 2006.—Vol. 14, no. 20. —P. 9203-9210.

115. Huang A., Gunn C., Li G.-L., Liang Y., Mirsaidi S., Narashimha A., and Pinguet T. A 10Gb/s photonic modulator and WDM MUX/DEMUX integrated with electronics in 0.13/spl mu/m SOI CMOS // 2006 IEEE International Solid State Circuits Conference-Digest of Technical Papers / IEEE. — 2006. — P. 922-929.

116. Fathololoumi S., Malouin C., Hui D., Al-Hemyari K., Nguyen K., Seddighian P., Chen Y.-J., Wang Y., Yan A., Defrees R., et al. Highly integrated 4 Tbps silicon photonic IC for compute fabric connectivity // 2022 IEEE Symposium on High-Performance Interconnects (HOTI) / IEEE. —2022. —P. 1-4.

117. Ahmed A. H., Lim D., Elmoznine A., Ma Y., Huynh T., Williams C., Vera L., Liu Y., Shi R., Streshinsky M., et al. 30.6 a 6v swing 3.6% thd¿ 40ghz driver with 4.5x bandwidth extension for a 272gb/s dual-polarization 16-qam silicon photonic transmitter // 2019 IEEE International Solid-State Circuits Conference-(ISSCC) / IEEE. — 2019. — P. 484-486.

118. Iqbal M., Gleeson M. A., Spaugh B., Tybor F., Gunn W. G., Hochberg M., Baehr-Jones T., Bailey R. C., and Gunn L. C. Label-free biosensor arrays based on silicon ring resonators and high-speed optical scanning instrumentation // IEEE Journal of selected topics in quantum electronics. —2010. —Vol. 16, no. 3. —P. 654-661.

119. Zhang X., Kwon K., Henriksson J., Luo J., and Wu M. C. A large-scale microelectromechanical-systems-based silicon photonics LiDAR // Nature. — 2022.—Vol. 603, no. 7900.—P. 253-258.

120. Raval M., Yaacobi A., and Watts M. R. Integrated visible light phased array system for autostereoscopic image projection // Optics Letters. — 2018.—Vol. 43, no. 15.—P. 36783681.

121. Seok T. J., Kwon K., Henriksson J., Luo J., and Wu M. C. Wafer-scale silicon photonic switches beyond die size limit // Optica. — 2019.—Vol. 6, no. 4.—P. 490-494.

122.

123.

124.

125.

126.

127.

128.

129.

130.

131

132.

133.

134.

135.

Shastri B. J., Tait A. N., Ferreira de Lima T., Pernice W. H., Bhaskaran H., Wright C. D., and Prucnal P. R. Photonics for artificial intelligence and neuromorphic computing // Nature Photonics. —2021. —Vol. 15, no. 2.—P. 102-114.

Ashtiani F., Geers A. J., and Aflatouni F. An on-chip photonic deep neural network for image classification // Nature.— 2022.— Vol. 606, no. 7914. —P. 501-506.

Bogaerts W., Perez D., Capmany J., Miller D. A., Poon J., Englund D., Morichetti F., and Melloni A. Programmable photonic circuits // Nature.—2020.—Vol. 586, no. 7828.— P. 207-216.

Reed B. D., Meyer M. J., Abramzon V., Ad O., Ad O., Adcock P., Ahmad F. R., Alppay G., Ball J. A., Beach J., et al. Real-time dynamic single-molecule protein sequencing on an integrated semiconductor device // Science. — 2022. — Vol. 378, no. 6616. — P. 186-192.

Punjabi N., Satija J., and Mukherji S. Evanescent wave absorption based fiber-optic sensor-cascading of bend and tapered geometry for enhanced sensitivity // Sensing Technology: Current Status and Future Trends III. — 2015. — P. 25-45.

Butt M. A. Dielectric waveguide-based sensors with enhanced evanescent field: unveiling the dynamic interaction with the ambient medium for biosensing and gas-sensing applications—a review // Photonics / MDPI.— 2024.— Vol. 11. —P. 198.

Butt M., Khonina S., and Kazanskiy N. Enhancement of evanescent field ratio in a silicon strip waveguide by incorporating a thin metal film // Laser Physics. — 2019. —Vol. 29, no. 7. —P. 076202.

Consani C., Dubois F., and Aubock G. Figures of merit for mid-IR evanescent-wave absorption sensors and their simulation by FEM methods // optics Express. — 2021. — Vol. 29, no. 7. — P. 9723-9736.

Liu J.-m. Photonic Devices. — Cambridge University Press, 2005. — P. 1-1028. — ISBN: 9780511614255.

Ranacher C., Tortschanoff A., Consani C., Jannesari R., Grille T., and Jakoby B. Numerical investigations of infrared slot waveguides for gas sensing // Proceedings / MDPI. — 2018. — Vol. 2. —P. 799.

Butt M. A. and Piramidowicz R. Standard slot waveguide and double hybrid plasmonic waveguide configurations for enhanced evanescent field absorption methane gas sensing // Photonics Letters of Poland. — 2022.—Vol. 14, no. 1.

Torrijos-Moran L., Griol A., and Garcia-Ruperez J. Experimental study of subwavelength grating bimodal waveguides as ultrasensitive interferometric sensors // Optics Letters. — 2019.—Vol. 44, no. 19. —P. 4702-4705.

Zemtsov D. S., Pshenichnyuk I. A., Kosolobov S. S., Zemtsova A. K., Zhigunov D. M., Smirnov A. S., Garbuzov K. N., and Drachev V. P. Plasmon-assisted Si-ITO integrated electro-optical rib-shape modulator // Journal of Lightwave Technology. — 2023. — Vol. 41, no. 19. —P. 6310-6314.

Kwon M.-S. Metal-insulator-silicon-insulator-metal waveguides compatible with standard CMOS technology // Optics Express. — 2011.—Vol. 19, no. 9. —P. 8379-8393.

136.

137.

138.

139.

140.

141

142.

143.

144.

145.

146.

147.

148.

149.

Lembrikov B. I., Ianetz D., and Ben-Ezra Y. Metal/Insulator/Metal (MIM) plasmonic waveguide containing a smectic A liquid crystal (SALC) layer // 2017 19th International Conference on Transparent Optical Networks (ICTON) / IEEE. — 2017. — P. 1-4.

Juan-Colas J., Johnson S., and Krauss T. F. Dual-mode electro-optical techniques for biosensing applications: a review // Sensors. — 2017.—Vol. 17, no. 9. — P. 2047.

Potdar R. P., Khollam Y. B., Shaikh S. F., Raut R. W., Pandit B., and More P. S. Evanescent wave sensor for potassium ion detection with special reference to agricultural application // Journal of Photochemistry and Photobiology A: Chemistry. — 2023. — Vol. 441. — P. 114707.

Zhao H., Zheng C., Pi M., Liang L., Song F., Zhang Y., Wang Y., and Tittel F. K. On-chip mid-infrared silicon-on-insulator waveguide methane sensor using two measurement schemes at 3.291 jm // Frontiers in Chemistry. — 2022.— Vol. 10. —P. 953684.

Song Y., Li B., Zhang H., Li M., Li Q., and He J.-J. Silicon waveguide sensors for carbon dioxide gas sensing in the mid-infrared region // Photonics / MDPI. — 2023.—Vol. 10.— P. 120.

Kumaar S. P. and Sivasubramanian A. Design of a high-sensitivity polymer double-slot waveguide sensor for point-of-care biomedical applications // Sensors International. — 2024. — Vol. 5. —P. 100255.

Barrios C. A. Optical slot-waveguide based biochemical sensors // Sensors. — 2009.—Vol. 9, no. 6. —P. 4751-4765.

Butt M., Khonina S., and Kazanskiy N. Modelling of Rib channel waveguides based on silicon-on-sapphire at 4.67 jm wavelength for evanescent field gas absorption sensor // Optik. —2018.—Vol. 168.—P. 692-697.

Khonina S. N., Kazanskiy N. L., and Butt M. A. Evanescent field ratio enhancement of a modified ridge waveguide structure for methane gas sensing application // IEEE Sensors Journal. —2020.—Vol. 20, no. 15.—P. 8469-8476.

Viphavakit C., Komodromos M., Themistos C., Mohammed W. S., Kalli K., and Azizur Rahman B. Optimization of a horizontal slot waveguide biosensor to detect DNA hybridization // Applied Optics. —2015. —Vol. 54, no. 15. —P. 4881-4888.

Zhou L., Sun X., Li X., and Chen J. Miniature microring resonator sensor based on a hybrid plasmonic waveguide // Sensors. — 2011. — Vol. 11, no. 7.—P. 6856-6867.

Butt M. A., Khonina S., and Kazanskiy N. Highly sensitive refractive index sensor based on hybrid plasmonic waveguide microring resonator // Waves in Random and Complex Media. —2020. —Vol. 30, no. 2. —P. 292-299.

Sun X., Dai D., Thylen L., and Wosinski L. High-sensitivity liquid refractive-index sensor based on a Mach-Zehnder interferometer with a double-slot hybrid plasmonic waveguide // Optics Express. —2015.—Vol. 23, no. 20. —P. 25688-25699.

Butt M. A., Shahbaz M., and Piramidowicz R. Racetrack ring resonator integrated with multimode interferometer structure based on low-cost silica-titania platform for refractive index sensing application // Photonics / MDPI. — 2023.—Vol. 10.—P. 978.

150. Butt M. A., Tyszkiewicz C., Wojtasik K., Karasinski P., Kazmierczak A., and Piramidowicz R. Subwavelength grating waveguide structures proposed on the low-cost silica-titania platform for optical filtering and refractive index sensing applications // International Journal of Molecular Sciences. — 2022.—Vol. 23, no. 12. —P. 6614.

151. Walter J.-G., Alwis L. S., Roth B., and Bremer K. All-optical planar polymer waveguide-based biosensor chip designed for smartphone-assisted detection of vitamin D // Sensors. — 2020.—Vol. 20, no. 23. —P. 6771.

152. Butt M. A., Kazanskiy N. L., and Khonina S. N. Modal characteristics of refractive index engineered hybrid plasmonic waveguide // IEEE Sensors Journal. — 2020. — Vol. 20, no. 17. — P. 9779-9786.

153. Butt M. A., Kazanskiy N., and Khonina S. On-chip symmetrically and asymmetrically transformed plasmonic Bragg grating formation loaded with a functional polymer for filtering and CO2 gas sensing applications // Measurement. — 2022. — Vol. 201. — P. 111694.

154. Ji L., Yang S., Shi R., Fu Y., Su J., and Wu C. Polymer waveguide coupled surface plasmon refractive index sensor: A theoretical study // Photonic Sensors. — 2020. — Vol. 10. — P. 353-363.

155. Milvich J., Kohler D., Freude W., and Koos C. Surface sensing with integrated optical waveguides: a design guideline // Optics express. — 2018.—Vol. 26, no. 16.—P. 1988519906.

156. TalebiFard S., Schmidt S., Shi W., Wu W., Jaeger N. A., Kwok E., Ratner D. M., and Chrostowski L. Optimized sensitivity of silicon-on-insulator (SOI) strip waveguide resonator sensor // Biomedical optics express. — 2017.—Vol. 8, no. 2.—P. 500-511.

157. Carlborg C. F., Gylfason K. B., Kazmierczak A., Dortu F., Polo M. B., Catala A. M., Kresbach G. M., Sohlstrom H., Moh T., Vivien L., et al. A packaged optical slot-waveguide ring resonator sensor array for multiplex label-free assays in labs-on-chips // Lab on a Chip. — 2010.—Vol. 10, no. 3. —P. 281-290.

158. Scullion M. G., Krauss T. F., and Di Falco A. Slotted photonic crystal sensors // Sensors.— 2013.—Vol. 13, no. 3. —P. 3675-3710.

159. Fard S. T., Donzella V., Schmidt S. A., Flueckiger J., Grist S. M., Talebi Fard P., Wu Y., Bojko R. J., Kwok E., Jaeger N. A., et al. Performance of ultra-thin SOI-based resonators for sensing applications // Optics express. — 2014. — Vol. 22, no. 12. — P. 14166-14179.

160. Gaur G., Hu S., Mernaugh R. L., Kravchenko I. I., Retterer S. T., and Weiss S. M. Labelfree detection of Herceptin® using suspended silicon microring resonators // Sensors and Actuators B: Chemical. — 2018. —Vol. 275. —P. 394-401.

161. Rodriguez G. A., Markov P., Cartwright A. P., Choudhury M. H., Afzal F. O., Cao T., Halimi S. I., Retterer S. T., Kravchenko I. I., and Weiss S. M. Photonic crystal nanobeam biosensors based on porous silicon // Optics Express. — 2019. — Vol. 27, no. 7. — P. 95369549.

162. Vollmer F. and Arnold S. Whispering-gallery-mode biosensing: label-free detection down to single molecules // Nature methods. — 2008.—Vol. 5, no. 7.—P. 591-596.

163

164.

165.

166.

167

168.

169.

170.

171.

172.

173.

174.

175.

176.

Armani A. M., Kulkarni R. P., Fraser S. E., Flagan R. C., and Vahala K. J. Label-free, single-molecule detection with optical microcavities // science. — 2007.—Vol. 317, no. 5839. —P. 783-787.

Zhu H., White I. M., Suter J. D., Dale P. S., and Fan X. Analysis of biomolecule detection with optofluidic ring resonator sensors // Optics Express. — 2007. — Vol. 15, no. 15.— P. 9139-9146.

Washburn A. L. and Bailey R. C. Photonics-on-a-chip: recent advances in integrated waveguides as enabling detection elements for real-world, lab-on-a-chip biosensing applications // Analyst. —2011. —Vol. 136, no. 2.—P. 227-236.

Foster M. A., Turner A. C., Lipson M., and Gaeta A. L. Nonlinear optics in photonic nanowires // Optics Express.— 2008.— Vol. 16, no. 2. —P. 1300-1320.

Chalyan T., Guider R., Pasquardini L., Zanetti M., Falke F., Schreuder E., Heideman R. G., Pederzolli C., and Pavesi L. Asymmetric Mach-Zehnder interferometer based biosensors for aflatoxin M1 detection // Biosensors. — 2016. — Vol. 6, no. 1. — P. 1.

Cheben P., Schmid J., Delage A., Densmore A., Janz S., Lamontagne B., Lapointe J., Post E., Waldron P., and Xu D.-X. A high-resolution silicon-on-insulator arrayed waveguide grating microspectrometer with sub-micrometer aperture waveguides // Optics express. — 2007. — Vol. 15, no. 5. —P. 2299-2306.

Cao H. Perspective on speckle spectrometers //J. Opt. — 2017. — Vol. 19, no. 6. — P. 060402.

Redding B., Liew S. F., Sarma R., and Cao H. Compact spectrometer based on a disordered photonic chip // Nature Photonics. — 2013. — Vol. 7, no. 9. — P. 746-751.

Varytis P., Huynh D.-N., Hartmann W., Pernice W., and Busch K. Design study of random spectrometers for applications at optical frequencies // Optics Letters. — 2018. — Vol. 43, no. 13. —P. 3180-3183.

Wen J., Shi W., Gao C., Liu Y., Feng S., Shao Y., Gao H., Shao Y., Zhang Y., Shen W., et al. A computational spectrometer for the visible, near, and mid-infrared enabled by a single-spinning film encoder // Communications Engineering. — 2025. — Vol. 4, no. 1.— P. 37.

Fritze M., Knecht J., Bozler C., Keast C., Fijol J., Jacobson S., Keating P., LeBlanc J., Fike E., Kessler B., et al. Fabrication of three-dimensional mode converters for silicon-based integrated optics // Journal of Vacuum Science & Technology B. — 2003. — Vol. 21, no. 6.— P. 2897-2902.

Vermeulen D. and Poulton C. V. Optical interfaces for silicon photonic circuits // Proceedings of the IEEE. —2018. —Vol. 106, no. 12. —P. 2270-2280.

Kopp C., Augendre E., Orobtchouk R., Lemonnier O., and Fedeli J.-M. Enhanced fiber grating coupler integrated by wafer-to-wafer bonding // Journal of Lightwave Technology. — 2011.—Vol. 29, no. 12. —P. 1847-1851.

Marchetti R., Lacava C., Carroll L., Gradkowski K., and Minzioni P. Coupling strategies for silicon photonics integrated chips // Photonics Research. — 2019.—Vol. 7, no. 2.— P. 201-239.

177. Vermeulen D., Selvaraja S., Verheyen P., Lepage G., Bogaerts W., Absil P., Van Thourhout D., and Roelkens G. High-efficiency fiber-to-chip grating couplers realized using an advanced CMOS-compatible silicon-on-insulator platform // Optics Express. — 2010.—Vol. 18, no. 17. —P. 18278-18283.

178. Gehring H., Blaicher M., Hartmann W., Varytis P., Busch K., Wegener M., and Pernice W. Low-loss fiber-to-chip couplers with ultrawide optical bandwidth // APL Photonics. — 2019.—Vol. 4, no. 1.—P. 010801.

179. Soganci I. M., La Porta A., and Offrein B. J. Flip-chip optical couplers with scalable I/O count for silicon photonics // Optics Express. — 2013. — Vol. 21, no. 13. — P. 16075-16085.

180. Brazas J. C. and Li L. Analysis of input-grating couplers having finite lengths // Applied Optics. —1995. —Vol. 34, no. 19. —P. 3786-3792.

181. Chen X., Li C., Fung C. K., Lo S. M., and Tsang H. K. Apodized waveguide grating couplers for efficient coupling to optical fibers // IEEE Photonics Technology Letters. — 2010. — Vol. 22, no. 15. —P. 1156-1158.

182. Scheerlinck S., Schrauwen J., Laere F. V., Taillaert D., Thourhout D. V., and Baets R. Efficient, broadband and compact metal grating couplers for silicon-on-insulator waveguides // Optics Express. —2007.—Vol. 15, no. 15. —P. 9625-9630.

183. Roelkens G., Van Thourhout D., and Baets R. High efficiency Silicon-on-Insulator grating coupler based on a poly-Silicon overlay // Optics Express. — 2006.—Vol. 14, no. 24.— P. 11622-11630.

184. Chen X. and Tsang H. K. Nanoholes grating couplers for coupling between silicon-on-insulator waveguides and optical fibers // IEEE Photonics Journal. — 2009.—Vol. 1, no. 3. — P. 184190.

185. Wang L., Ren J., Han X., Claes T., Jian X., Bienstman P., Baets R., Zhao M., and Morthier G. A label-free optical biosensor built on a low-cost polymer platform // IEEE Photonics Journal. —2012. —Vol. 4, no. 3. —P. 920-930.

186. De Goede M., Dijkstra M., Obregon R., Ramon-Azcon J., Martinez E., Padilla L., Mitjans F., and Garcia-Blanco S. M. Al2O3 microring resonators for the detection of a cancer biomarker in undiluted urine // Optics Express. — 2019.—Vol. 27, no. 13. —P. 18508-18521.

187. Watanabe K., Kishi Y., Hachuda S., Watanabe T., Sakemoto M., Nishijima Y., and Baba T. Simultaneous detection of refractive index and surface charges in nanolaser biosensors // Applied Physics Letters. — 2015.— Vol. 106, no. 2. —P. 021106.

188. Luo R., Jiang H., Liang H., Chen Y., and Lin Q. Self-referenced temperature sensing with a lithium niobate microdisk resonator // Optics letters. — 2017.—Vol. 42, no. 7.— P. 1281-1284.

189. Arya S. K., Wong C. C., Jeon Y. J., Bansal T., and Park M. K. Advances in complementary-metal-oxide-semiconductor-based integrated biosensor arrays // Chemical reviews. — 2015. — Vol. 115, no. 11. —P. 5116-5158.

190. Wang J., Sanchez M. M., Yin Y., Herzer R., Ma L., and Schmidt O. G. Silicon-based integrated label-free optofluidic biosensors: latest advances and roadmap // Advanced Materials Technologies. — 2020.—Vol. 5, no. 6. —P. 1901138.

191.

192.

193.

194.

195.

196.

197.

198.

199.

200.

201.

202.

203.

204.

Shang K., Pathak S., Guan B., Liu G., and Yoo S. Low-loss compact multilayer silicon nitride platform for 3D photonic integrated circuits // Optics Express. — 2015. — Vol. 23, no. 16. —P. 21334-21342.

Blumenthal D. J., Heideman R., Geuzebroek D., Leinse A., and Roeloffzen C. Silicon nitride in silicon photonics // Proceedings of the IEEE. — 2018.—Vol. 106, no. 12. —P. 2209-2231.

Porcel M. A., Hinojosa A., Jans H., Stassen A., Goyvaerts J., Geuzebroek D., Geiselmann M., Dominguez C., and Artundo I. Silicon nitride photonic integration for visible light applications // Optics & Laser Technology. — 2019.—Vol. 112. —P. 299-306.

Baets R., Subramanian A. Z., Clemmen S., Kuyken B., Zhao H., Raza A., Van Laer R., Leo F., Dhakal A., Selvaraja S. K., et al. Silicon Photonics: silicon nitride versus silicon-on-insulator // Optical Fiber Communication Conference / OSA. — 2016. — P. Th3J-1.

Munoz P., Mico G., Bru L. A., Pastor D., Perez D., Domenech J. D., Fernández J., Baños R., Gargallo B., Alemany R., et al. Silicon nitride photonic integration platforms for visible, near-infrared and mid-infrared applications // Sensors. — 2017. — Vol. 17, no. 9.—P. 2088.

Munoz P., van Dijk P. W., Geuzebroek D., Geiselmann M., Dominguez C., Stassen A., Domenech J. D., Zervas M., Leinse A., Roeloffzen C. G., et al. Foundry developments toward silicon nitride photonics from visible to the mid-infrared // IEEE Journal of Selected Topics in Quantum Electronics. — 2019.—Vol. 25, no. 5. — P. 1-13.

Arbabi A. and Goddard L. L. Measurements of the refractive indices and thermo-optic coefficients of Si3N4 and SiO x using microring resonances // Optics letters. — 2013. — Vol. 38, no. 19. —P. 3878-3881.

Terry S. C., Jerman J. H., and Angell J. B. A gas chromatographic air analyzer fabricated on a silicon wafer // IEEE Transactions on Electron Devices. — 1979. — Vol. 26, no. 12. — P. 1880-1886.

Manz A., Graber N., and Widmer H. M. Miniaturized total chemical analysis systems: a novel concept for chemical sensing // Sensors and Actuators B: Chemical. —1990. — Vol. 1, no. 1-6. —P. 244-248.

Keeping S. C., Binz D., Howell C. E., Jamson L., Mead R. A., Greensted C. L., and Coe D. E. Micro-filtration. — 2006. — US Patent 7,066,336. Access mode: https://patents.google.com/ patent/US7066336B2/en.

Shen P.-C., Su C., Lin Y., Chou A.-S., Cheng C.-C., Park J.-H., Chiu M.-H., Lu A.-Y., Tang H.-L., Tavakoli M. M., et al. Ultralow contact resistance between semimetal and monolayer semiconductors // Nature. — 2021.—Vol. 593, no. 7858. — P. 211-217.

Iijima S. and Ichihashi T. Single-shell carbon nanotubes of 1-nm diameter // Nature. — 1993. —Vol. 363, no. 6430. —P. 603-605.

Novoselov K. S., Geim A. K., Morozov S. V., Jiang D.-e., Zhang Y., Dubonos S. V., Grigorieva I. V., and Firsov A. A. Electric field effect in atomically thin carbon films // Science. —2004. —Vol. 306, no. 5696. —P. 666-669.

Wang L., Boutilier M. S., Kidambi P. R., Jang D., Hadjiconstantinou N. G., and Karnik R. Fundamental transport mechanisms, fabrication and potential applications of nanoporous atomically thin membranes // Nature Nanotechnology. — 2017.—Vol. 12, no. 6. — P. 509522.

205

206

207

208

209

210

211

212

213

214

215

216

217

218

219

Tiwari S. K., Bhat S., and Mahato K. K. Design and fabrication of low-cost microfluidic channel for biomedical application // Scientific Reports. — 2020. — Vol. 10, no. 1. — P. 9215.

Squires T. M. and Quake S. R. Microfluidics: Fluid physics at the nanoliter scale // Reviews of Modern Physics. —2005. —Vol. 77, no. 3. —P. 977-1026.

Bocquet L. and Tabeling P. Physics and technological aspects of nanofluidics // Lab on a Chip. —2014.—Vol. 14, no. 17. —P. 3143-3158.

You Y., Ismail A., Nam G.-H., Goutham S., Keerthi A., and Radha B. Angstrofluidics: walking to the limit // Annual Review of Materials Research. — 2022. —Vol. 52. —P. 189218.

Chen L., Yang C., Xiao Y., Yan X., Hu L., Eggersdorfer M., Chen D., Weitz D., and Ye F. Millifluidics, microfluidics, and nanofluidics: manipulating fluids at varying length scales // Materials Today Nano. — 2021.—Vol. 16.—P. 100136.

Sackmann E. K., Fulton A. L., and Beebe D. J. The present and future role of microfluidics in biomedical research // Nature. — 2014.—Vol. 507, no. 7491. —P. 181-189.

Yager P., Edwards T., Fu E., Helton K., Nelson K., Tam M. R., and Weigl B. H. Microfluidic diagnostic technologies for global public health // Nature. — 2006.—Vol. 442, no. 7101.— P. 412-418.

Sparreboom W., van den Berg A., and Eijkel J. C. Principles and applications of nanofluidic transport // Nature Nanotechnology.— 2009.— Vol. 4, no. 11.—P. 713-720.

SHI P., YAN X., WANG X., FENG L., and CHEN D. One-step fabrication of biocompatible oil-core microcapsules with controlled release // CIESC Journal. — 2020. — Vol. 72, no. 1.— P. 619.

Zhang J., Liu Y., Sun J., Gu R., Ma C., and Liu K. Biological fibers based on naturally sourced proteins: Mechanical investigation and applications // Materials Today Advances. — 2020.—Vol. 8. —P. 100095.

Sun Z., Wu B., Ren Y., Wang Z., Zhao C.-X., Hai M., Weitz D. A., and Chen D. Diverse particle carriers prepared by co-precipitation and phase separation: Formation and applications // ChemPlusChem.— 2021.— Vol. 86, no. 1.—P. 49-58.

Zare R. N. and Kim S. Microfluidic platforms for single-cell analysis // Annual Review of Biomedical Engineering. —2010.—Vol. 12.—P. 187-201.

Song C., Gao D., Yuan T., Chen Y., Liu L., Chen X., and Jiang Y. Microfluidic three-dimensional biomimetic tumor model for studying breast cancer cell migration and invasion in the presence of interstitial flow // Chinese Chemical Letters. — 2019. — Vol. 30, no. 5.— P. 1038-1042.

Bessoth F. G., deMello A. J., and Manz A. Microstructure for efficient continuous flow mixing // Analytical Communications. — 1999. — Vol. 36, no. 6.—P. 213-215.

Franke T., Abate A. R., Weitz D. A., and Wixforth A. Surface acoustic wave (SAW) directed droplet flow in microfluidics for PDMS devices // Lab on a Chip. — 2009. — Vol. 9, no. 18. — P. 2625-2627.

220. Schmid L., Weitz D. A., and Franke T. Sorting drops and cells with acoustics: acoustic microfluidic fluorescence-activated cell sorter // Lab on a Chip. — 2014. — Vol. 14, no. 19.— P. 3710-3718.

221. Shang L., Cheng Y., and Zhao Y. Emerging droplet microfluidics // Chemical reviews.— 2017.—Vol. 117, no. 12. —P. 7964-8040.

222. Huh D., Matthews B. D., Mammoto A., Montoya-Zavala M., Hsin H. Y., and Ingber D. E. Reconstituting organ-level lung functions on a chip // Science. — 2010.—Vol. 328, no. 5986. —P. 1662-1668.

223. Jiang K., Jokhun D. S., and Lim C. T. Microfluidic detection of human diseases: From liquid biopsy to COVID-19 diagnosis // Journal of Biomechanics. — 2021.—Vol. 117. — P. 110235.

224. Wolfe D. B., Conroy R. S., Garstecki P., Mayers B. T., Fischbach M. A., Paul K. E., Prentiss M., and Whitesides G. M. Dynamic control of liquid-core/liquid-cladding optical waveguides // Proceedings of the National Academy of Sciences. — 2004.—Vol. 101, no. 34. —P. 12434-12438.

225. Wang H., Park M., Dong R., Kim J., Cho Y.-K., Tlusty T., and Granick S. Boosted molecular mobility during common chemical reactions // Science. — 2020.—Vol. 369, no. 6503.— P. 537-541.

226. Mea H. J., Delgadillo L., and Wan J. On-demand modulation of 3D-printed elastomers using programmable droplet inclusions // Proceedings of the National Academy of Sciences. — 2020.—Vol. 117, no. 26. —P. 14790-14797.

227. Gaut N. J. and Adamala K. P. Toward artificial photosynthesis // Science. — 2020. — Vol. 368, no. 6491. —P. 587-588.

228. Zhou J., Khodakov D. A., Ellis A. V., and Voelcker N. H. Surface modification for PDMS-based microfluidic devices // Electrophoresis. — 2012.—Vol. 33, no. 1. — P. 89-104.

229. Wang Z. and Zhang T. Microfluidics Devices: Fabrication and Surface Modification // Microfluidics: Fundamental, Devices and Applications. — John Wiley and Sons, Ltd, 2018.— P. 113-145. —ISBN: 9783527800643.

230. Total Exosome Isolation Reagent : Thermo Fisher Scientific. — 2023. — Access mode: https://www.thermofisher.com/order/catalog/product/4478359 (online; accessed: 2024-0315).

231. Eloquence™ Exosome RNA-seq Kit : System Biosciences. — 2022. — Access mode: https: //www.systembio.com/products/exosome-research/exosome-isolation (online; accessed: 202403-15).

232. Exo-spin™ Exosome Purification Kits : Cell Guidance Systems. — 2021. — Access mode: https://www.cellgs.com/product/exo-spin-exosome-purification-kits/ (online; accessed: 202403-15).

233. miRCURY Exosome Serum/Plasma Kit : Qiagen. — 2023. — Access mode: https: //www.qiagen.com/us/products/discovery-and-translational-research/exosome-research/ mircury-exosome-serum-plasma-kit/ (online; accessed: 2024-03-15).

234. Yang K., Lin H.-Y., Curley C., et al. Castro bead-based extracellular vesicle analysis using flow cytometry // Adv. Biosys. — 2020. — P. 2000203.

235

236

237

238

239

240

241

242

243

244

245

246

247

248

249

250

Yashchenok A., Chernyshev V., Konovalova E., et al. AntiCD63 oligonucleotide functionalized magnetic beads for the rapid isolation of small extracellular vesicles and detection of EpCAM and HER2 membrane receptors using DARPin probes // Analysis & Sensing. — 2022. — P. e202200059.

Method for Isolation and Analysis of Exosomes Yashchenok A., Chernyshev V., German S., et al. ; OOO "TETRAKVANT" (RU) ; G01N33/5005. — no. 2022102303.

Rufo J., Cai F., Friend J., Wiklund M., and Huang T. J. Acoustofluidics for biomedical applications // Nature Reviews Methods Primers. — 2022. — Vol. 2, no. 1. — P. 30.

Nakamura C., Inuyama Y., Shirai K., Sugimoto N., and Miyake J. Detection of porphyrin using a short peptide immobilized on a surface plasmon resonance sensor chip // Biosensors and Bioelectronics. — 2001.— Vol. 16, no. 9-12.—P. 1095-1100.

Emili A. Q. and Cagney G. Large-scale functional analysis using peptide or protein arrays // Nature biotechnology.— 2000.— Vol. 18, no. 4.—P. 393-397.

Jelinek R. and Kolusheva S. Carbohydrate biosensors // Chemical reviews. — 2004. — Vol. 104, no. 12. —P. 5987-6016.

Tsukruk V. V. and Bliznyuk V. N. Adhesive and friction forces between chemically modified silicon and silicon nitride surfaces // Langmuir. — 1998. — Vol. 14, no. 2. — P. 446-455.

Turkova J. Oriented immobilization of biologically active proteins as a tool for revealing protein interactions and function // Journal of Chromatography B: Biomedical Sciences and Applications. —1999. —Vol. 722, no. 1. —P. 11-31.

Knopp D., Tang D., and Niessner R. Bioanalytical applications of biomolecule-functionalized nanometer-sized doped silica particles // Analytica chimica acta. — 2009. —Vol. 647, no. 1. — P. 14-30.

Homola J. Electromagnetic theory of surface plasmons // Surface plasmon resonance based sensors. — 2006. — P. 3-44.

Norde W. Adsorption of proteins from solution at the solid-liquid interface // Advances in colloid and interface science. — 1986. — Vol. 25. — P. 267-340.

Brogan K. L., Wolfe K. N., Jones P. A., and Schoenfisch M. H. Direct oriented immobilization of F (ab) antibody fragments on gold // Analytica chimica acta. — 2003.—Vol. 496, no. 1-2. —P. 73-80.

Bagiyan G., Koroleva I., Soroka N., and Ufimtsev A. Oxidation of thiol compounds by molecular oxygen in aqueous solutions // Russian chemical bulletin. — 2003. — Vol. 52.— P. 1135-1141.

Savage M. Avidin-biotin Chemistry: A Handbook. —Pierce Chemical Company, 1992. — P. 1-467. —ISBN: 9780935940114.

Rashid J. I. A. and Yusof N. A. The strategies of DNA immobilization and hybridization detection mechanism in the construction of electrochemical DNA sensor: A review // Sensing and bio-sensing research. — 2017.—Vol. 16.—P. 19-31.

Huertas C. S., Calvo-Lozano O., Mitchell A., and Lechuga L. M. Advanced evanescent-wave optical biosensors for the detection of nucleic acids: An analytic perspective // Frontiers in chemistry. —2019.—Vol. 7. —P. 724.

251

252

253

254

255

256

257

258

259

260

261

262

263

264

Lapin N. A. and Chabal Y. J. Infrared characterization of biotinylated silicon oxide surfaces, surface stability, and specific attachment of streptavidin // The Journal of Physical Chemistry B. —2009. —Vol. 113, no. 25.—P. 8776-8783.

Vos K. D., Bartolozzi I., Schacht E., Bienstman P., and Baets R. Silicon-on-Insulator microring resonator for sensitive and label-free biosensing // Optics express. — 2007. — Vol. 15, no. 12. —P. 7610-7615.

Yao Z., Wu K., Tan B. X., Wang J., Li Y., Zhang Y., and Poon A. W. Integrated silicon photonic microresonators: emerging technologies // IEEE Journal of Selected Topics in Quantum Electronics. — 2018.—Vol. 24, no. 6. —P. 1-24.

Kou R., Kobayashi Y., Inoue S., Tsuchizawa T., Ueno Y., Suzuki S., Hibino H., Yamamoto T., Nakajima H., and Yamada K. Dopamine detection on activated reaction field consisting of graphene-integrated silicon photonic cavity // Optics Express. — 2019. — Vol. 27, no. 22.— P. 32058-32068.

Vorobyeva A., Schulga A., Konovalova E., Guler R., Lofblom J., Sandstrom M., Garousi J., Chernov V., Bragina O., Orlova A., et al. Optimal composition and position of histidine-containing tags improves biodistribution of 99mTc-labeled DARPin G3 // Scientific Reports. — 2019.—Vol. 9, no. 1.—P. 9405.

Zhang P., He M., and Zeng Y. Ultrasensitive microfluidic analysis of circulating exosomes using a nanostructured graphene oxide/polydopamine coating // Lab on a Chip. — 2016. — Vol. 16, no. 16. —P. 3033-3042.

Lee K., Shao H., Weissleder R., and Lee H. Acoustic purification of extracellular microvesi-cles // ACS nano. —2015.—Vol. 9, no. 3.—P. 2321-2327.

Lv X., Geng Z., Su Y., Fan Z., Wang S., Fang W., and Chen H. Label-free exosome detection based on a low-cost plasmonic biosensor array integrated with microfluidics // Langmuir. — 2019.—Vol. 35, no. 30. —P. 9816-9824.

Singh P. SPR biosensors: historical perspectives and current challenges // Sensors and actuators B: Chemical.— 2016.— Vol. 229. —P. 110-130.

Lv C., Hu C., Luo J., Liu S., Qiao Y., Zhang Z., Song J., Shi Y., Cai J., and Watanabe A. Recent advances in graphene-based humidity sensors // Nanomaterials. — 2019.—Vol. 9, no. 3. —P. 422.

Blank T., Eksperiandova L., and Belikov K. Recent trends of ceramic humidity sensors development: A review // Sensors and Actuators B: Chemical. — 2016. — Vol. 228. — P. 416-442.

Dastgeer G., Shahzad Z. M., Chae H., Kim Y. H., Ko B. M., and Eom J. Bipolar junction transistor exhibiting excellent output characteristics with a prompt response against the selective protein // Advanced Functional Materials. — 2022.—Vol. 32, no. 38. —P. 2204781.

Manikandan V., Sikarwar S., Yadav B., and Mane R. Fabrication of tin substituted nickel ferrite (Sn-NiFe2O4) thin film and its application as opto-electronic humidity sensor // Sensors and Actuators A: Physical. — 2018.— Vol. 272. —P. 267-273.

Yao Y. and Ma W. Self-assembly of polyelectrolytic/graphene oxide multilayer thin films on quartz crystal microbalance for humidity detection // IEEE Sensors Journal. — 2014. — Vol. 14, no. 11. —P. 4078-4084.

265

266

267

268

269

270.

271

272.

273.

274.

275.

276.

277.

278.

Zhou G., Byun J.-H., Oh Y., Jung B.-M., Cha H.-J., Seong D.-G., Um M.-K., Hyun S., and Chou T.-W. Highly sensitive wearable textile-based humidity sensor made of high-strength, single-walled carbon nanotube/poly (vinyl alcohol) filaments // ACS applied materials & interfaces. —2017. —Vol. 9, no. 5. —P. 4788-4797.

Dastgeer G., Afzal A. M., Jaffery S. H. A., Imran M., Assiri M. A., and Nisar S. Gate modulation of the spin current in graphene/WSe2 van der Waals heterostructure at room temperature // Journal of Alloys and Compounds. — 2022. — Vol. 919. — P. 165815.

Altug H., Oh S.-H., Maier S. A., and Homola J. Advances and applications of nanophotonic biosensors // Nature nanotechnology. — 2022. — Vol. 17, no. 1.—P. 5-16.

Wang J., Maier S. A., and Tittl A. Trends in Nanophotonics-Enabled Optofluidic Biosensors // Advanced Optical Materials. — 2022.—Vol. 10, no. 7. —P. 2102366.

Kindt J. T. and Bailey R. C. Biomolecular analysis with microring resonators: applications in multiplexed diagnostics and interaction screening // Current opinion in chemical biology. — 2013.—Vol. 17, no. 5. —P. 818-826.

Kuzin A., Chernyshev V., Kovalyuk V., An P., Golikov A., Ozhegov R., Gorin D., Gippius N., and Goltsman G. Hybrid nanophotonic-microfluidic sensor for highly sensitive liquid and gas analyses // Optics Letters.— 2022.— Vol. 47, no. 9.—P. 2358-2361.

Sharma T., Wang J., Kaushik B. K., Cheng Z., Kumar R., Wei Z., and Li X. Review of recent progress on silicon nitride-based photonic integrated circuits // IEEE Access. — 2020. — Vol. 8. —P. 195436-195446.

Li H. and Fan X. Characterization of sensing capability of optofluidic ring resonator biosensors // Applied Physics Letters.— 2010.— Vol. 97, no. 1.—P. 011105.

Ermatov T., Noskov R. E., Machnev A. A., Gnusov I., Atkin V., Lazareva E. N., German S. V., Kosolobov S. S., Zatsepin T. S., Sergeeva O. V., et al. Multispectral sensing of biological liquids with hollow-core microstructured optical fibres // Light: Science & Applications.— 2020.—Vol. 9, no. 1.—P. 173.

Dwivedi R., Kumar A., and Tripathi S. M. Ultra high sensitive refractive index sensor using a metal under-clad ridge waveguide modal interferometer near the dispersion turning point // IEEE Sensors Journal. — 2020.—Vol. 21, no. 4. —P. 4674-4681.

Pandey A., Gupta P., Vairagi K., and Mondal S. K. Packaged negative axicon optical fiber probe and Bessel beam interferometry for refractive index measurement of hazardous liquid samples // Journal of Lightwave Technology. — 2019.—Vol. 37, no. 24.—P. 6121-6126.

Zhang X., Zhou C., Luo Y., Yang Z., Zhang W., Li L., Xu P., Zhang P., and Xu T. High Q-factor, ultrasensitivity slot microring resonator sensor based on chalcogenide glasses // Optics Express. —2022.—Vol. 30, no. 3. —P. 3866-3875.

Cheng W., Sun X., Ye S., Yuan B., Sun Y., Marsh J. H., and Hou L. Sidewall grating slot waveguide microring resonator biochemical sensor // Optics Letters. — 2023. —Vol. 48, no. 19. —P. 5113-5116.

Zhang Z., Yang J., He X., Zhang J., Huang J., Chen D., and Han Y. Plasmonic refractive index sensor with high figure of merit based on concentric-rings resonator // Sensors. — 2018.—Vol. 18, no. 1. —P. 116.

279.

280

281

282

283

284

285

286

287

288

289

290

291

292

Li H., Wu L., Jin Y., and Wu A. High Sensitivity Refractive Index Sensor Based on Trapezoidal Subwavelength Grating Slot Microring Resonator // IEEE Photonics Journal. — 2023.—Vol. 15, no. 4. —P. 1-6.

De Goede M., Dijkstra M., Obregon R., Ramon-Azcon J., Martinez E., Padilla L., Mitjans F., and Garcia-Blanco S. M. Al 2 O 3 microring resonators for the detection of a cancer biomarker in undiluted urine // Optics express.— 2019.— Vol. 27, no. 13. —P. 18508-18521.

De Vos K., Girones J., Claes T., De Koninck Y., Popelka S., Schacht E., Baets R., and Bienstman P. Multiplexed antibody detection with an array of silicon-on-insulator microring resonators // IEEE Photonics Journal.— 2009.— Vol. 1, no. 4. —P. 225-235.

De Vos K., Bartolozzi I., Schacht E., Bienstman P., and Baets R. Silicon-on-Insulator microring resonator for sensitive and label-free biosensing // Optics express. — 2007. — Vol. 15, no. 12. —P. 7610-7615.

Sergeeva A. S., Volkova E. K., Bratashov D. N., Shishkin M. I., Atkin V. S., Markin A. V., Skaptsov A. A., Volodkin D. V., and Gorin D. A. Layer-by-layer assembled highly absorbing hundred-layer films containing a phthalocyanine dye: Fabrication and photosensibilization by thermal treatment // Thin Solid Films.— 2015.— Vol. 583. —P. 60-69.

Wulfkuhle J. D., Liotta L. A., and Petricoin E. F. Proteomic applications for the early detection of cancer // Nature Reviews Cancer. — 2003.—Vol. 3, no. 4.—P. 267-275.

McDermott U., Downing J. R., and Stratton M. R. Genomics and the continuum of cancer care // New England Journal of Medicine. — 2011.—Vol. 364, no. 4. —P. 340-350.

Dhawan A. P., Heetderks W. J., Pavel M., Acharya S., Akay M., Mairal A., Wheeler B., Dacso C. C., Sunder T., Lovell N., Gerber M., Shah M., Senthilvel S. G., Wang M. D., and Bhargava B. Current and future challenges in point-of-care technologies: a paradigm-shift in affordable global healthcare with personalized and preventive medicine // IEEE Journal of Translational Engineering in Health and Medicine. — 2015. — Vol. 3.—P. 1-10.

Yager P., Domingo G. J., and Gerdes J. Point-of-care diagnostics for global health // Annual Review of Biomedical Engineering. — 2008. — Vol. 10. — P. 107-144.

Arlett J., Myers E., and Roukes M. Comparative advantages of mechanical biosensors // Nature Nanotechnology. — 2011.—Vol. 6, no. 4.—P. 203-215.

Roberts P., Couny F., Sabert H., Mangan B., Williams D., Farr L., Mason M., Tomlinson A., Birks T., Knight J., and J R. P. S. Ultimate low loss of hollow-core photonic crystal fibres // Optics Express. —2005.—Vol. 13, no. 1. —P. 236-244.

Yang L., Sun H., Jiang W., Xu T., Song B., Peng R., Han L., and Jia L. A chemical method for specific capture of circulating tumor cells using label-free polyphenol-functionalized films // Chemistry of Materials. — 2018. —Vol. 30, no. 13.—P. 4372-4382.

Pongruengkiat W. and Pechprasarn S. Whispering-gallery mode resonators for detecting cancer // Sensors.— 2017.— Vol. 17, no. 9. —P. 2095.

Luchansky M. S., Washburn A. L., McClellan M. S., and Bailey R. C. Sensitive on-chip detection of a protein biomarker in human serum and plasma over an extended dynamic range using silicon photonic microring resonators and sub-micron beads // Lab on a Chip. — 2011.—Vol. 11, no. 12. —P. 2042-2044.

293. Psarouli A., Botsialas A., Salapatas A., Stefanitsis G., Nikita D., Jobst G., Chaniotakis N., Goustouridis D., Makarona E., Petrou P. S., et al. Fast label-free detection of C-reactive protein using broad-band Mach-Zehnder interferometers integrated on silicon chips // Talanta. —

2017.—Vol. 165. —P. 458-465.

294. Martens D., Ramirez-Priego P., Murib M. S., Elamin A. A., Gonzalez-Guerrero A. B., Stehr M., Jonas F., Anton B., Hlawatsch N., Soetaert P., et al. A low-cost integrated biosensing platform based on SiN nanophotonics for biomarker detection in urine // Analytical methods. —2018. —Vol. 10, no. 25. —P. 3066-3073.

295. Luchansky M. S. and Bailey R. C. Rapid, multiparameter profiling of cellular secretion using silicon photonic microring resonator arrays // Journal of the American Chemical Society. — 2011.—Vol. 133, no. 50. —P. 20500-20506.

296. Scheler O., Kindt J. T., Qavi A. J., Kaplinski L., Glynn B., Barry T., Kurg A., and Bailey R. C. Label-free, multiplexed detection of bacterial tmRNA using silicon photonic microring resonators // Biosensors and Bioelectronics. — 2012. — Vol. 36, no. 1. — P. 56-61.

297. Ramirez-Priego P., Martens D., Elamin A. A., Soetaert P., Van Roy W., Vos R., Anton B., Bockstaele R., Becker H., Singh M., et al. Label-free and real-time detection of tuberculosis in human urine samples using a nanophotonic point-of-care platform // ACS sensors. —

2018.—Vol. 3, no. 10. —P. 2079-2086.

298. Liu Q., Lim B. K. L., Lim S. Y., Tang W. Y., Gu Z., Chung J., Park M. K., and Barkham T. Label-free, real-time and multiplex detection of Mycobacterium tuberculosis based on silicon photonic microring sensors and asymmetric isothermal amplification technique (SPMS-AIA) // Sensors and Actuators B: Chemical.— 2018.— Vol. 255. —P. 1595-1603.

299. Wu S., Guo Y., Wang W., Zhou J., and Zhang Q. Label-free biosensing using a microring resonator integrated with poly-(dimethylsiloxane) microfluidic channels // Review of Scientific Instruments. —2019.—Vol. 90, no. 3. —P. 035004.

300. Chakravarty S., Lai W.-C., Zou Y., Drabkin H. A., Gemmill R. M., Simon G. R., Chin S. H., and Chen R. T. Multiplexed specific label-free detection of NCI-H358 lung cancer cell line lysates with silicon based photonic crystal microcavity biosensors // Biosensors and Bioelectronics. —2013.—Vol. 43. —P. 50-55.

301. Fukuyama M., Nishida M., Abe Y., Amemiya Y., Ikeda T., Kuroda A., and Yokoyama S. Detection of antigen-antibody reaction using Si ring optical resonators functionalized with an immobilized antibody-binding protein // Japanese Journal of Applied Physics. — 2011. — Vol. 50, no. 4S. — P. 04DL07.

302. Yang C.-J., Yan H., Tang N., Zou Y., Al-Hadeethi Y., Xu X., Dalir H., and Chen R. T. Ultra sensitivity silicon-based photonic crystal microcavity biosensors for plasma protein detection in patients with pancreatic cancer // Micromachines. — 2020. — Vol. 11, no. 3.—P. 282.

303. Liu Q., Shin Y., Kee J. S., Kim K. W., Rafei S. R. M., Perera A. P., Tu X., Lo G.-Q., Ricci E., Colombel M., et al. Mach-Zehnder interferometer (MZI) point-of-care system for rapid multiplexed detection of microRNAs in human urine specimens // Biosensors and Bioelectronics. —2015.—Vol. 71. —P. 365-372.

304. Vaisocherova H., Brynda E., and Homola J. Functionalizable low-fouling coatings for labelfree biosensing in complex biological media: advances and applications // Analytical and bioanalytical chemistry. — 2015.— Vol. 407, no. 14. —P. 3927-3953.

305. Jeyachandran Y. L., Mielczarski J. A., Mielczarski E., and Rai B. Efficiency of blocking of non-specific interaction of different proteins by BSA adsorbed on hydrophobic and hydrophilic surfaces // Journal of colloid and interface science. — 2010. — Vol. 341, no. 1. — P. 136-142.

306. Mukundan H., Xie H., Anderson A. S., Grace W. K., Shively J. E., and Swanson B. I. Optimizing a waveguide-based sandwich immunoassay for tumor biomarkers: evaluating fluorescent labels and functional surfaces // Bioconjugate chemistry. — 2009.—Vol. 20, no. 2. —P. 222-230.

307. Riquelme M., Zhao H., Srinivasaraghavan V., Pruden A., Vikesland P., and Agah M. Optimizing blocking of nonspecific bacterial attachment to impedimetric biosensors // Sens. Bio-Sensing Res. —2016.—Vol. 8. —P. 47-54.

308. Glover F. and Goulden J. Relationship between refractive index and concentration of solutions // Nature. —1963. —Vol. 200, no. 4912. —P. 1165-1166.

309. Kuzin A., Kovalyuk V., Golikov A., Prokhodtsov A., Marakhin A., Ferrari S., Pernice W., Gippius N., and Goltsman G. Efficiency of focusing grating couplers versus taper length and angle // Journal of Physics: Conference Series / IOP Publishing. — 2019.—Vol. 1410.— P. 012181.

310. Benedikter B. J., Bouwman F. G., Vajen T., Heinzmann A. C., Grauls G., Mariman E. C., Wouters E. F., Savelkoul P. H., Lopez-Iglesias C., Koenen R. R., et al. Ultrafiltration combined with size exclusion chromatography efficiently isolates extracellular vesicles from cell culture media for compositional and functional studies // Scientific Reports. — 2017.— Vol. 7, no. 1.—P. 15297.

311. Yashchenok A. M., Chernyshev V. S., Konovalova E. V., Kholodenko R., Tsydenzhapova E., Shipunova V. O., Schulga A. A., Deyev S. M., and Gorin D. A. Anti-CD63-Oligonucleotide Functionalized Magnetic Beads for the Rapid Isolation of Small Extracellular Vesicles and Detection of EpCAM and HER2 Membrane Receptors using DARPin Probes // Analysis & Sensing. —2023.—Vol. 3, no. 2.—P. e202200059.

312. Sokolova E., Proshkina G., Kutova O., Shilova O., Ryabova A., Schulga A., Stremovskiy O., Zdobnova T., Balalaeva I., and Deyev S. Recombinant targeted toxin based on HER2-specific DARPin possesses a strong selective cytotoxic effect in vitro and a potent antitumor activity in vivo // Journal of Controlled Release. — 2016. — Vol. 233. — P. 48-56.

313. Cardenes B., Clares I., Bezos T., Toribio V., Lopez-Martin S., Rocha A., Peinado H., Yanez-Mo M., and Cabanas C. ALCAM/CD166 is involved in the binding and uptake of cancer-derived extracellular vesicles // International Journal of Molecular Sciences. — 2022. — Vol. 23, no. 10. —P. 5753.

314. Yuan D., Dong Y., Liu Y., and Li T. Mach-Zehnder interferometer biochemical sensor based on silicon-on-insulator rib waveguide with large cross section // Sensors. — 2015.—Vol. 15, no. 9. —P. 21500-21517.

315. White I. M. and Fan X. On the performance quantification of resonant refractive index sensors // Optics express.— 2008.— Vol. 16, no. 2. —P. 1020-1028.

316. Yariv A. Critical coupling and its control in optical waveguide-ring resonator systems // IEEE Photonics Technology Letters. — 2002.—Vol. 14, no. 4. —P. 483-485.

317. Hariharan P. and Braun C. Basics of interferometry // Applied Optics. — 1992.—Vol. 31, no. 31. —P. 6583.

318.

319.

320.

321.

322.

323.

324.

325.

326.

327.

328

329

330

331

Liew S. F., Redding B., Choma M. A., Tagare H. D., and Cao H. Broadband multimode fiber spectrometer // Optics letters. — 2016.— Vol. 41, no. 9. —P. 2029-2032.

Li H., Wu X., Liu G., Vinu R., Wang X., Chen Z., and Pu J. Generation of controllable spectrum in multiple positions from speckle patterns // Optics & Laser Technology. — 2022.—Vol. 149. —P. 107820.

García-Merino J., Mercado-Zúñiga C., Torres-Sanmiguel C., and Torres-Torres C. Mechano-optical effects in multiwall carbon nanotubes ethanol based nanofluids // Optics Express. — 2018.—Vol. 26, no. 2. —P. 2033-2038.

Kuzin A. Y., Elmanov I., Kovalyuk V., An P., and Goltsman G. Silicon nitride focusing grating coupler for input and output light of NV-centers // Proceedings of the 32nd European Modeling & Simulation Symposium. — 2020. — P. 349-353.

Elmanova A., Elmanov I., An P., Kovalyuk V., Kuzin A., Golikov A., and Goltsman G. Characterization of focusing grating couplers for telecom wavelengths in the first and second diffraction order // Journal of Physics: Conference Series / IOP Publishing. — 2021.— Vol. 2086. —P. 012052.

An P., Kovalyuk V., Golikov A., Zubkova E., Ferrari S., Korneev A., Pernice W., and Goltsman G. Experimental optimisation of O-ring resonator Q-factor for on-chip spontaneous four wave mixing // Journal of Physics: Conference Series / IOP Publishing. — 2018. — Vol. 1124. —P. 051047.

Luan E., Shoman H., Ratner D. M., Cheung K. C., and Chrostowski L. Silicon photonic biosensors using label-free detection // Sensors. — 2018.—Vol. 18, no. 10.—P. 3519.

Komma J., Schwarz C., Hofmann G., Heinert D., and Nawrodt R. Thermo-optic coefficient of silicon at 1550 nm and cryogenic temperatures // Applied Physics Letters. — 2012.—Vol. 101, no. 4. —P. 041905.

Elshaari A. W., Zadeh I. E., Jons K. D., and Zwiller V. Thermo-optic characterization of silicon nitride resonators for cryogenic photonic circuits // IEEE Photonics Journal. — 2016.—Vol. 8, no. 3.—P. 1-9.

Pasquini C. Near infrared spectroscopy: fundamentals, practical aspects and analytical applications // Journal of the Brazilian chemical society. — 2003.—Vol. 14. — P. 198-219.

Chen M. and Weng F. Kramers-Kronig analysis of leaf refractive index with the PROSPECT leaf optical property model // Journal of Geophysical Research: Atmospheres. — 2012.— Vol. 117, no. D18.

Paschotta R. Kramers-Kronig relations are mathematical relations between absorption and refractive index of media.—RP Photonics AG, 2006.—Access mode: https://www. rp-photonics.com/kramers_kronig_relations.html (online; accessed: 2025-03-15).

Barclay P. E., Srinivasan K., and Painter O. Nonlinear response of silicon photonic crystal microresonators excited via an integrated waveguide and fiber taper // Optics express. — 2005.—Vol. 13, no. 3. —P. 801-820.

Hale G. and Querry M. Optical constants of water in the 200-nm to 200-^m wavelength region. — https://refractiveindex.mfo/?shelf=3d&book=liqmds&page=water. — 1973. — [Online; accessed 01-February-2023].

332

333

334

335

336

337

338

339

340

341

342

343

344

345

Myers T. L., Tonkyn R. G., Danby T. O., Taubman M. S., Bernacki B. E., Birnbaum J. C., Sharpe S. W., and Johnson T. J. Accurate measurement of the optical constants n and k for a series of 57 inorganic and organic liquids for optical modeling and detection // Applied spectroscopy. —2018.—Vol. 72, no. 4. —P. 535-550.

Kou L., Labrie D., and Chylek P. Refractive indices of water and ice in the 0.65-to 2.5-^m spectral range // Applied optics. — 1993. — Vol. 32, no. 19. — P. 3531-3540.

Vlasov V. I., Kuzin A. Y., Florya I. N., Buriak N. S., Chernyshev V. S., Golikov A. D., Krasnov L. V., Mikhailov S. E., Pugach M. A., Nasibulin A. G., et al. Hybrid nanophotonic-microfluidic sensor integrated with machine learning for operando state-of-charge monitoring in vanadium flow batteries // Journal of Energy Storage. — 2025. — Vol. 111.—P. 115349.

Hale G. M. and Querry M. R. Optical constants of water in the 200-nm to 200-^m wavelength region // Applied optics. — 1973.—Vol. 12, no. 3. — P. 555-563.

Lau H. H., Murney R., Yakovlev N. L., Novoselova M. V., Lim S. H., Roy N., Singh H., Sukhorukov G. B., Haigh B., and Kiryukhin M. V. Protein-tannic acid multilayer films: A multifunctional material for microencapsulation of food-derived bioactives // Journal of Colloid and Interface Science. — 2017.—Vol. 505. —P. 332-340.

Lorber B., Fischer F., Bailly M., Roy H., and Kern D. Protein analysis by dynamic light scattering: Methods and techniques for students // Biochemistry and Molecular Biology Education. —2012. —Vol. 40, no. 6. —P. 372-382.

Sung H. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries // CA: A Cancer Journal for Clinicians. — 2021.—Vol. 71, no. 3. —P. 209-249.

Malignant Neoplasms in Russia in 2020 (Morbidity and Mortality) / ed. by Kaprin A., Starinsky V., and Shakhzadova A. — Moscow : P.A. Hertsen Moscow Oncology Research Institute - Branch of the National Medical Research Radiological Center, 2021. — P. 252.— ISBN: 978-5-85569-128-6.

Ministry of Health of the Russian Federation. Clinical Guidelines: Breast Cancer. — 2021. — [Electronic resource]. Access mode: https://oncology-association.ru/wp-content/uploads/ 2021/02/rak-molochnoj-zhelezy-2021.pdf (online; accessed: 2025-03-16).

Tang P. and Tse G. Immunohistochemical surrogates for molecular classification of breast carcinoma: a 2015 update // Archives of Pathology & Laboratory Medicine. — 2016. — Vol. 140, no. 8. —P. 806-814.

Wang Y., Ikeda D., Narasimhan B., et al. Estrogen receptor-negative invasive breast cancer: imaging features of tumors with and without human epidermal growth factor receptor type 2 overexpression // Radiology. — 2008. — Vol. 246, no. 2. — P. 367-375.

Kennecke H., Yerushalmi R., Woods R., et al. Metastatic behavior of breast cancer subtypes // Journal of Clinical Oncology. — 2010.—Vol. 28, no. 20. —P. 3271-3277.

Wu Q., Li J., Zhu S., et al. Breast cancer subtypes predict the preferential site of distant metastases: a SEER based study // Oncotarget. — 2017.— Vol. 8, no. 17. —P. 27990-27996.

Wolff A., Hammond M., Hicks D., et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update // Archives of Pathology & Laboratory Medicine.— 2014.— Vol. 138, no. 2. —P. 241-256.

346.

347.

348.

349.

350.

351.

352.

353.

354.

355

356

357

358

359

360

361

Venetis K., Crimini E., Sajjadi E., et al. HER2 low, ultra-low, and novel complementary biomarkers: Expanding the spectrum of HER2 positivity in breast cancer // Frontiers in Molecular Biosciences.— 2022.— Vol. 9.—P. 834651.

Luo L., Wu Z., Wang Y., et al. Regulating the production and biological function of small extracellular vesicles: current strategies, applications and prospects // Journal of Nanobiotechnology. — 2021.— Vol. 19.—P. 422.

Chen Y., Zhao Y., Yin Y., et al. Mechanism of cargo sorting into small extracellular vesicles // Bioengineered. — 2021.— Vol. 12, no. 1.—P. 8186-8201.

Whiteside T. Tumor-derived exosomes and their role in cancer progression // Advances in Clinical Chemistry. —2016.—Vol. 74. —P. 103-141.

Li F., Liu J., Xu F., et al. Role of tumor-derived exosomes in bone metastasis // Oncology Letters. —2019.—Vol. 18, no. 4. —P. 3935-3945.

Kalluri R. The biology and function of exosomes in cancer // Journal of Clinical Investigation. — 2016.—Vol. 126, no. 4.—P. 1208-1215.

Becker A., Thakur B., Weiss J., et al. Extracellular vesicles in cancer: Cell-to-cell mediators of metastasis // Cancer Cell.— 2016.— Vol. 30, no. 6. —P. 836-848.

Dong X., Bai X., Ni J., et al. Exosomes and breast cancer drug resistance // Cell Death & Disease. —2020.—Vol. 11.—P. 987.

Yuan X., Qian N., Ling S., et al. Breast cancer exosomes contribute to pre-metastatic niche formation and promote bone metastasis of tumor cells // Theranostics. — 2021. — Vol. 11, no. 3. —P. 1429-1445.

Wang X., Sun C., Huang X., et al. The advancing roles of exosomes in breast cancer // Frontiers in Cell and Developmental Biology. — 2021.—Vol. 9. — P. 731062.

Marar C., Starich B., and Wirtz D. Extracellular vesicles in immunomodulation and tumor progression // Nature Immunology. — 2021. — Vol. 22, no. 5. — P. 560-570.

Xiao L., Hareendran S., and Loh Y. Function of exosomes in neurological disorders and brain tumors // Extracellular Vesicles and Circulating Nucleic Acids. — 2021. — Vol. 2.— P. 55-79.

Andreu Z., Masia E., Charbonnier D., and Vicent M. A rapid, convergent approach to the identification of exosome inhibitors in breast cancer models // Nanotheranostics. — 2023. — Vol. 7, no. 1.—P. 1-21.

Zhou B., Xu K., Zheng X., et al. Application of exosomes as liquid biopsy in clinical diagnosis // Signal Transduction and Targeted Therapy. — 2020. — Vol. 5, no. 1. — P. 144.

Kabe Y., Suematsu M., Sakamoto S., et al. Development of a highly sensitive device for counting the number of disease-specific exosomes in human sera // Clinical Chemistry. — 2018.—Vol. 64, no. 10. —P. 1463-1473.

Nanou A., Zeune L., Bidard F., et al. HER2 expression on tumor-derived extracellular vesicles and circulating tumor cells in metastatic breast cancer // Breast Cancer Research. — 2020.—Vol. 22. —P. 86.

362. Zhang Z., Zhang L., Yu G., et al. Exosomal miR-1246 and miR-155 as predictive and prognostic biomarkers for trastuzumab-based therapy resistance in HER2-positive breast cancer // Cancer Chemotherapy and Pharmacology. — 2020. — Vol. 86, no. 6. — P. 761-772.

363. Zhang H., Yan C., and Wang Y. Exosome-mediated transfer of circHIPK3 promotes trastuzumab chemoresistance in breast cancer // Journal of Drug Targeting. — 2021.— Vol. 29, no. 9. —P. 1004-1015.

364. Qian X., Qu H., Zhang F., et al. Exosomal long noncoding RNA AGAP2-AS1 regulates trastuzumab resistance via inducing autophagy in breast cancer // American Journal of Cancer Research.— 2021.— Vol. 11, no. 5.—P. 1962-1981.

365. Zaytsev V., Kuzin A., Panda K., Chernyshev V., Florya I., Fedorov F. S., Kovalyuk V., Golikov A., An P. P., Khlebstov B. N., et al. Convective assembly of silica colloidal particles inside photonic integrated chip-based microfluidic systems for gas sensing applications // Nanoscale. —2024.—Vol. 16, no. 37. —P. 17365-17370.