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Biosensors
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Microfluidic Bio-Sensors and Their Applications
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Microfluidic Bio-Sensors and Their Applications

A special issue of Biosensors (ISSN 2079-6374). This special issue belongs to the section "Biosensor and Bioelectronic Devices".

Deadline for manuscript submissions: closed (10 December 2022) | Viewed by 42489

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Dr. Krishna Kant

E-Mail Website
Guest Editor
Centro De Investigaciones Biomédicas (CINBIO), Universidade de Vigo, 36310 Vigo, Spain
Interests: microfluidic sensing; electrochemical bio-sensing; point-of-care diagnostics; precision diagnostics; plasmonic sensing; microfluidic devices; lab-on-chip
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The integration of microfluidics and sensing technology is a rapidly developing field with major applications towards diagnostic devices, including rapid detection for food safety, chemical and biological research, medical diagnostics, and environmental monitoring. This Special Issue is dedicated to covering innovations over a variety of topics in this area, from sensing to manufacturing and integration methods to novel microfluidic-based sensors for biological application. Articles reporting on the latest developments in multiplexed sensors and other types of sensor integrated with microfluidics are of interest, including electrochemical, optical, magnetic, and other transduction types.

I am very pleased to invite you to contribute to this Special Issue on “Microfluidic Bio-Sensors and Their Applications”, which are emerging research subjects with various applications. The scope of the journal is wide on biosensing, including but not limited to the following areas:

  • Lab-on-a-chip and other biochips and microarray systems;
  • Novel microfluidic based biosensing concepts, mechanisms, and detection principles;
  • 3D printed microfluidic and biosensing devices;
  • Development of biosensor methodologies and applications;
  • Fabrication technology of chip-based detection devices;
  • Scaffold based biomimetic systems and microfluidic devices for biosensing application;
  • Biological and chemical actuators, including smart materials and microfluidic components;
  • Biophotonic sensors and chemical sensing systems.

Research articles and detailed comprehensive review reports on recent development in the field as well as achievements and new fabrication technologies claimed to be relevant to biosensing and actuation will be considered for publication. This Special Issue is addressed at biologists, microfluidic experts, 3D bio printing and cell culture experts, etc.

Dr. Krishna Kant
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biosensors is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Point-of-care (PoC)
  • Diagnostics
  • Molecular imprinted polymer biosensing
  • Multiplexed biosensing
  • Bio-inspired materials
  • Cell and tissue sensors
  • 3D printing
  • Microfluidic devices
  • Lab-on-chip

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Published Papers (11 papers)

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Editorial

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2 pages, 163 KiB  
Editorial
Microfluidic Bio-Sensors and Their Applications
by Krishna Kant
Biosensors 2023, 13(9), 843; https://doi.org/10.3390/bios13090843 - 24 Aug 2023
Cited by 2 | Viewed by 1557
Abstract
Biosensors are a promising tool for a wide variety of target analyte detection and enable point-of-care diagnostics with reduced volume and space [...] Full article
(This article belongs to the Special Issue Microfluidic Bio-Sensors and Their Applications)

Research

Jump to: Editorial, Review

14 pages, 7884 KiB  
Article
Microfluidic-Assisted Synthesis of Metal—Organic Framework —Alginate Micro-Particles for Sustained Drug Delivery
by Akhilesh Bendre, Vinayak Hegde, Kanalli V. Ajeya, Subrahmanya Thagare Manjunatha, Derangula Somasekhara, Varalakshmi K. Nadumane, Krishna Kant, Ho-Young Jung, Wei-Song Hung and Mahaveer D. Kurkuri
Biosensors 2023, 13(7), 737; https://doi.org/10.3390/bios13070737 - 17 Jul 2023
Cited by 13 | Viewed by 2866
Abstract
Drug delivery systems (DDS) are continuously being explored since humans are facing more numerous complicated diseases than ever before. These systems can preserve the drug’s functionality and improve its efficacy until the drug is delivered to a specific site within the body. One [...] Read more.
Drug delivery systems (DDS) are continuously being explored since humans are facing more numerous complicated diseases than ever before. These systems can preserve the drug’s functionality and improve its efficacy until the drug is delivered to a specific site within the body. One of the least used materials for this purpose are metal—organic frameworks (MOFs). MOFs possess many properties, including their high surface area and the possibility for the addition of functional surface moieties, that make them ideal drug delivery vehicles. Such properties can be further improved by combining different materials (such as metals or ligands) and utilizing various synthesis techniques. In this work, the microfluidic technique is used to synthesize Zeolitic Imidazole Framework-67 (ZIF-67) containing cobalt ions as well as its bimetallic variant with cobalt and zinc as ZnZIF-67 to be subsequently loaded with diclofenac sodium and incorporated into sodium alginate beads for sustained drug delivery. This study shows the utilization of a microfluidic approach to synthesize MOF variants. Furthermore, these MOFs were incorporated into a biopolymer (sodium alginate) to produce a reliable DDS which can perform sustained drug releases for up to 6 days (for 90% of the full amount released), whereas MOFs without the biopolymer showed sudden release within the first day. Full article
(This article belongs to the Special Issue Microfluidic Bio-Sensors and Their Applications)
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14 pages, 5806 KiB  
Article
Quantitative, Temperature-Calibrated and Real-Time Glucose Biosensor Based on Symmetrical-Meandering-Type Resistor and Intertwined Capacitor Structure
by Yangchuan Ma, Tian Qiang, Minjia Gao, Junge Liang and Yanfeng Jiang
Biosensors 2021, 11(12), 484; https://doi.org/10.3390/bios11120484 - 28 Nov 2021
Cited by 7 | Viewed by 3212
Abstract
Here, we propose a glucose biosensor with the advantages of quantification, excellent linearity, temperature-calibration function, and real-time detection based on a resistor and capacitor, in which the resistor works as a temperature sensor and the capacitor works as a biosensor. The resistor has [...] Read more.
Here, we propose a glucose biosensor with the advantages of quantification, excellent linearity, temperature-calibration function, and real-time detection based on a resistor and capacitor, in which the resistor works as a temperature sensor and the capacitor works as a biosensor. The resistor has a symmetrical meandering type structure that increases the contact area, leading to variations in resistance and effective temperature monitoring of a glucose solution. The capacitor is designed with an intertwined structure that fully contacts the glucose solution, so that capacitance is sensitively varied, and high sensitivity monitoring can be realized. Moreover, a polydimethylsiloxane microfluidic channel is applied to achieve a fixed shape, a fixed point, and quantitative measurements, which can eliminate influences caused by fluidity, shape, and thickness of the glucose sample. The glucose solution in a temperature range of 25–100 °C is measured with variations of 0.2716 Ω/°C and a linearity response of 0.9993, ensuring that the capacitor sensor can have reference temperature information before detecting the glucose concentration, achieving the purpose of temperature calibration. The proposed capacitor-based biosensor demonstrates sensitivities of 0.413 nF/mg·dL−1, 0.048 nF/mg·dL−1, and 0.011 pF/mg·dL−1; linearity responses of 0.96039, 0.91547, and 0.97835; and response times less than 1 second, respectively, at DC, 1 kHz, and 1 MHz for a glucose solution with a concentration range of 25–1000 mg/dL. Full article
(This article belongs to the Special Issue Microfluidic Bio-Sensors and Their Applications)
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12 pages, 4420 KiB  
Article
RFID-Based Microwave Biosensor for Non-Contact Detection of Glucose Solution
by Minjia Gao, Tian Qiang, Yangchuan Ma, Junge Liang and Yanfeng Jiang
Biosensors 2021, 11(12), 480; https://doi.org/10.3390/bios11120480 - 26 Nov 2021
Cited by 9 | Viewed by 3896
Abstract
Due to the increasing number of diabetic patients, early monitoring of glucose levels is particularly important; therefore, glucose biosensors have attracted enormous attention from researchers. In this paper, we propose a glucose microwave biosensor based on RFID and achieve a non-contact measurement of [...] Read more.
Due to the increasing number of diabetic patients, early monitoring of glucose levels is particularly important; therefore, glucose biosensors have attracted enormous attention from researchers. In this paper, we propose a glucose microwave biosensor based on RFID and achieve a non-contact measurement of the concentration of glucose solutions. The Reader is a complementary split-ring resonator (CSRR), and the Tag is comprised of a squared spiral capacitor (SSC). A polydimethylsiloxane microfluidic quantitative cavity with a volume of 1.56 μL is integrated on the Tag to ensure that the glucose solution can be accurately set to the sensitive area and fully contacted with the electromagnetic flux. Because the SSC exhibits different capacitances when it contacts glucose solutions of different concentrations, changing the resonant frequency of the CSRR, we can use the relationship to characterize the biosensing response. Measurement results show that bare CSRR and RFID-based biosensors have achieved sensitivities of 0.31 MHz/mg·dL−1 and 10.27 kHz/mg·dL−1, and detection limits of 13.79 mg/dL and 1.19 mg/dL, respectively, and both realize a response time of less than 1 s. Linear regression analysis of the abovementioned biosensors showed an excellent linear relationship. The proposed design provides a feasible solution for microwave biosensors aiming for the non-contact measurement of glucose concentration. Full article
(This article belongs to the Special Issue Microfluidic Bio-Sensors and Their Applications)
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12 pages, 2667 KiB  
Article
Sequence-Independent DNA Adsorption on Few-Layered Oxygen-Functionalized Graphene Electrodes: An Electrochemical Study for Biosensing Application
by Narges Asefifeyzabadi, Torrey E. Holland, Poopalasingam Sivakumar, Saikat Talapatra, Ishani M. Senanayake, Boyd M. Goodson and Mohtashim H. Shamsi
Biosensors 2021, 11(8), 273; https://doi.org/10.3390/bios11080273 - 14 Aug 2021
Cited by 8 | Viewed by 3508
Abstract
DNA is strongly adsorbed on oxidized graphene surfaces in the presence of divalent cations. Here, we studied the effect of DNA adsorption on electrochemical charge transfer at few-layered, oxygen-functionalized graphene (GOx) electrodes. DNA adsorption on the inkjet-printed GOx electrodes caused [...] Read more.
DNA is strongly adsorbed on oxidized graphene surfaces in the presence of divalent cations. Here, we studied the effect of DNA adsorption on electrochemical charge transfer at few-layered, oxygen-functionalized graphene (GOx) electrodes. DNA adsorption on the inkjet-printed GOx electrodes caused amplified current response from ferro/ferricyanide redox probe at concentration range 1 aM–10 nM in differential pulse voltammetry. We studied a number of variables that may affect the current response of the interface: sequence type, conformation, concentration, length, and ionic strength. Later, we showed a proof-of-concept DNA biosensing application, which is free from chemical immobilization of the probe and sensitive at attomolar concentration regime. We propose that GOx electrodes promise a low-cost solution to fabricate a highly sensitive platform for label-free and chemisorption-free DNA biosensing. Full article
(This article belongs to the Special Issue Microfluidic Bio-Sensors and Their Applications)
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15 pages, 1931 KiB  
Article
Rapid Multianalyte Microfluidic Homogeneous Immunoassay on Electrokinetically Driven Beads
by Pierre-Emmanuel Thiriet, Danashi Medagoda, Gloria Porro and Carlotta Guiducci
Biosensors 2020, 10(12), 212; https://doi.org/10.3390/bios10120212 - 21 Dec 2020
Cited by 4 | Viewed by 3961
Abstract
The simplicity of homogeneous immunoassays makes them suitable for diagnostics of acute conditions. Indeed, the absence of washing steps reduces the binding reaction duration and favors a rapid and compact device, a critical asset for patients experiencing life-threatening diseases. In order to maximize [...] Read more.
The simplicity of homogeneous immunoassays makes them suitable for diagnostics of acute conditions. Indeed, the absence of washing steps reduces the binding reaction duration and favors a rapid and compact device, a critical asset for patients experiencing life-threatening diseases. In order to maximize analytical performance, standard systems employed in clinical laboratories rely largely on the use of high surface-to-volume ratio suspended moieties, such as microbeads, which provide at the same time a fast and efficient collection of analytes from the sample and controlled aggregation of collected material for improved readout. Here, we introduce an integrated microfluidic system that can perform analyte detection on antibody-decorated beads and their accumulation in confined regions within 15 min. We employed the system to the concomitant analysis of clinical concentrations of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Cystatin C in serum, two acute kidney injury (AKI) biomarkers. To this end, high-aspect-ratio, three-dimensional electrodes were integrated within a microfluidic channel to impart a controlled trajectory to antibody-decorated microbeads through the application of dielectrophoretic (DEP) forces. Beads were efficiently retained against the fluid flow of reagents, granting an efficient on-chip analyte-to-bead binding. Electrokinetic forces specific to the beads’ size were generated in the same channel, leading differently decorated beads to different readout regions of the chip. Therefore, this microfluidic multianalyte immunoassay was demonstrated as a powerful tool for the rapid detection of acute life-threatening conditions. Full article
(This article belongs to the Special Issue Microfluidic Bio-Sensors and Their Applications)
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13 pages, 2532 KiB  
Article
Development of a Pharmacogenetic Lab-on-Chip Assay Based on the In-Check Technology to Screen for Genetic Variations Associated to Adverse Drug Reactions to Common Chemotherapeutic Agents
by Rosario Iemmolo, Valentina La Cognata, Giovanna Morello, Maria Guarnaccia, Mariamena Arbitrio, Enrico Alessi and Sebastiano Cavallaro
Biosensors 2020, 10(12), 202; https://doi.org/10.3390/bios10120202 - 9 Dec 2020
Cited by 3 | Viewed by 2919
Abstract
Background: Antineoplastic agents represent the most common class of drugs causing Adverse Drug Reactions (ADRs). Mutant alleles of genes coding for drug-metabolizing enzymes are the best studied individual risk factors for these ADRs. Although the correlation between genetic polymorphisms and ADRs is well-known, [...] Read more.
Background: Antineoplastic agents represent the most common class of drugs causing Adverse Drug Reactions (ADRs). Mutant alleles of genes coding for drug-metabolizing enzymes are the best studied individual risk factors for these ADRs. Although the correlation between genetic polymorphisms and ADRs is well-known, pharmacogenetic tests are limited to centralized laboratories with expensive or dedicated instrumentation used by specialized personnel. Nowadays, DNA chips have overcome the major limitations in terms of sensibility, specificity or small molecular detection, allowing the simultaneous detection of several genetic polymorphisms with time and costs-effective advantages. In this work, we describe the design of a novel silicon-based lab-on-chip assay able to perform low-density and high-resolution multi-assay analysis (amplification and hybridization reactions) on the In-Check platform. Methods: The novel lab-on-chip was used to screen 17 allelic variants of three genes associated with adverse reactions to common chemotherapeutic agents: DPYD (Dihydropyrimidine dehydrogenase), MTHFR (5,10-Methylenetetrahydrofolate reductase) and TPMT (Thiopurine S-methyltransferase). Results: Inter- and intra assay variability were performed to assess the specificity and sensibility of the chip. Linear regression was used to assess the optimal hybridization temperature set at 52 °C (R2 ≈ 0.97). Limit of detection was 50 nM. Conclusions: The high performance in terms of sensibility and specificity of this lab-on-chip supports its further translation to clinical diagnostics, where it may effectively promote precision medicine. Full article
(This article belongs to the Special Issue Microfluidic Bio-Sensors and Their Applications)
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17 pages, 14279 KiB  
Article
Gas Crosstalk between PFPE–PEG–PFPE Triblock Copolymer Surfactant-Based Microdroplets and Monitoring Bacterial Gas Metabolism with Droplet-Based Microfluidics
by Sunghyun Ki and Dong-Ku Kang
Biosensors 2020, 10(11), 172; https://doi.org/10.3390/bios10110172 - 11 Nov 2020
Cited by 8 | Viewed by 5378
Abstract
The PFPE–PEG–PFPE (Perfluoropolyether-polyethylene glycol-perfluoropolyether) surfactant has been used in droplet-based microfluidics and is known to provide high droplet stability and biocompatibility. Since this surfactant ensures the stability of droplets, droplet-based microfluidic systems have been widely used to encapsulate and analyze various biological components [...] Read more.
The PFPE–PEG–PFPE (Perfluoropolyether-polyethylene glycol-perfluoropolyether) surfactant has been used in droplet-based microfluidics and is known to provide high droplet stability and biocompatibility. Since this surfactant ensures the stability of droplets, droplet-based microfluidic systems have been widely used to encapsulate and analyze various biological components at the single-molecule scale, including viruses, bacteria, nucleic acids and proteins. In this study, we experimentally confirmed that gas crosstalk occurred between droplets formed by fluorinated oil and the PFPE–PEG–PFPE surfactant. E. coli K-12 bacterial cells were encapsulated with Luria–Bertani broth within droplets for the cultivation, and gas crosstalk was identified with neighboring droplets that contain phenol red. Since bacteria produce ammonia gas during its metabolism, penetration of ammonia gas initiates a color change of phenol red-containing droplets. Ammonia gas exchange was also confirmed by reacting ammonium chloride and sodium hydroxide within droplets that encapsulated. Herein, we demonstrate the gas crosstalk issue between droplets when it is formed using the PFPE–PEG–PFPE surfactant and also confirm that the density of droplet barrier has effects on gas crosstalk. Our results also suggest that droplet-based microfluidics can be used for the monitoring of living bacteria by the determination of bacterial metabolites during cultivation. Full article
(This article belongs to the Special Issue Microfluidic Bio-Sensors and Their Applications)
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13 pages, 2622 KiB  
Article
The Effect of Optically Induced Dielectrophoresis (ODEP)-Based Cell Manipulation in a Microfluidic System on the Properties of Biological Cells
by Po-Yu Chu, Chia-Hsun Hsieh, Chien-Ru Lin and Min-Hsien Wu
Biosensors 2020, 10(6), 65; https://doi.org/10.3390/bios10060065 - 16 Jun 2020
Cited by 23 | Viewed by 4873
Abstract
Cell manipulation using optically induced dielectrophoresis (ODEP) in microfluidic systems has attracted the interest of scientists due to its simplicity. Although this technique has been successfully demonstrated for various applications, one fundamental issue has to be addressed—Whether, the ODEP field affects the native [...] Read more.
Cell manipulation using optically induced dielectrophoresis (ODEP) in microfluidic systems has attracted the interest of scientists due to its simplicity. Although this technique has been successfully demonstrated for various applications, one fundamental issue has to be addressed—Whether, the ODEP field affects the native properties of cells. To address this issue, we explored the effect of ODEP electrical conditions on cellular properties. Within the experimental conditions tested, the ODEP-based cell manipulation with the largest velocity occurred at 10 Vpp and 1 MHz, for the two cancer cell types explored. Under this operating condition, however, the cell viability of cancer cells was significantly affected (e.g., 70.5 ± 10.0% and 50.6 ± 9.2% reduction for the PC-3 and SK-BR-3 cancer cells, respectively). Conversely, the exposure of cancer cells to the ODEP electrical conditions of 7–10 Vpp and 3–5 MHz did not significantly alter the cell viability, cell metabolic activity, and the EpCAM, VIM, and ABCC1 gene expression of cancer cells. Overall, this study fundamentally investigated the effect of ODEP electrical conditions on the cellular properties of cancer cells. The information obtained is crucially important for the utilization of ODEP-based cell manipulation in a microscale system for various applications. Full article
(This article belongs to the Special Issue Microfluidic Bio-Sensors and Their Applications)
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Review

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19 pages, 3860 KiB  
Review
Role of Paper-Based Sensors in Fight against Cancer for the Developing World
by Amey Dukle, Arputharaj Joseph Nathanael, Balaji Panchapakesan and Tae-Hwan Oh
Biosensors 2022, 12(9), 737; https://doi.org/10.3390/bios12090737 - 7 Sep 2022
Cited by 8 | Viewed by 2480
Abstract
Cancer is one of the major killers across the globe. According to the WHO, more than 10 million people succumbed to cancer in the year 2020 alone. The early detection of cancer is key to reducing the mortality rate. In low- and medium-income [...] Read more.
Cancer is one of the major killers across the globe. According to the WHO, more than 10 million people succumbed to cancer in the year 2020 alone. The early detection of cancer is key to reducing the mortality rate. In low- and medium-income countries, the screening facilities are limited due to a scarcity of resources and equipment. Paper-based microfluidics provide a platform for a low-cost, biodegradable micro-total analysis system (µTAS) that can be used for the detection of critical biomarkers for cancer screening. This work aims to review and provide a perspective on various available paper-based methods for cancer screening. The work includes an overview of paper-based sensors, the analytes that can be detected and the detection, and readout methods used. Full article
(This article belongs to the Special Issue Microfluidic Bio-Sensors and Their Applications)
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33 pages, 3765 KiB  
Review
Recent Advances in Microfluidic Platform for Physical and Immunological Detection and Capture of Circulating Tumor Cells
by Mahesh Padmalaya Bhat, Venkatachalam Thendral, Uluvangada Thammaiah Uthappa, Kyeong-Hwan Lee, Madhuprasad Kigga, Tariq Altalhi, Mahaveer D. Kurkuri and Krishna Kant
Biosensors 2022, 12(4), 220; https://doi.org/10.3390/bios12040220 - 7 Apr 2022
Cited by 31 | Viewed by 6218
Abstract
CTCs (circulating tumor cells) are well-known for their use in clinical trials for tumor diagnosis. Capturing and isolating these CTCs from whole blood samples has enormous benefits in cancer diagnosis and treatment. In general, various approaches are being used to separate malignant cells, [...] Read more.
CTCs (circulating tumor cells) are well-known for their use in clinical trials for tumor diagnosis. Capturing and isolating these CTCs from whole blood samples has enormous benefits in cancer diagnosis and treatment. In general, various approaches are being used to separate malignant cells, including immunomagnets, macroscale filters, centrifuges, dielectrophoresis, and immunological approaches. These procedures, on the other hand, are time-consuming and necessitate multiple high-level operational protocols. In addition, considering their low efficiency and throughput, the processes of capturing and isolating CTCs face tremendous challenges. Meanwhile, recent advances in microfluidic devices promise unprecedented advantages for capturing and isolating CTCs with greater efficiency, sensitivity, selectivity and accuracy. In this regard, this review article focuses primarily on the various fabrication methodologies involved in microfluidic devices and techniques specifically used to capture and isolate CTCs using various physical and biological methods as well as their conceptual ideas, advantages and disadvantages. Full article
(This article belongs to the Special Issue Microfluidic Bio-Sensors and Their Applications)
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