Label-Free Optical Resonator-Based Biosensors

The demand for biosensor technology has grown drastically over the last few decades, mainly in disease diagnosis, drug development, and environmental health and safety. Optical resonator-based biosensors have been widely exploited to achieve highly sensitive, rapid, and label-free detection of biological analytes. The advancements in microfluidic and micro/nanofabrication technologies allow them to be miniaturized and simultaneously detect various analytes in a small sample volume. By virtue of these advantages and advancements, the optical resonator-based biosensor is considered a promising platform not only for general medical diagnostics but also for point-of-care applications. This review aims to provide an overview of recent progresses in label-free optical resonator-based biosensors published mostly over the last 5 years. We categorized them into Fabry-Perot interferometer-based and whispering gallery mode-based biosensors. The principles behind each biosensor are concisely introduced, and recent progresses in configurations, materials, test setup, and light confinement methods are described. Finally, the current challenges and future research topics of the optical resonator-based biosensor are discussed.

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Demonstration of a Label-Free and Low-Cost Optical Cavity-Based Biosensor Using Streptavidin and C-Reactive Protein

Biosensors ◽

10.3390/bios11010004 ◽

2020 ◽

Vol 11 (1) ◽

pp. 4

Author(s):

Donggee Rho ◽

Seunghyun Kim

Keyword(s):

Limit Of Detection ◽

Point Of Care ◽

Low Cost ◽

Optical Cavity ◽

Sample Volume ◽

Small Sample ◽

Label Free ◽

C Reactive Protein ◽

Reactive Protein ◽

Cavity Structure

An optical cavity-based biosensor (OCB) has been developed for point-of-care (POC) applications. This label-free biosensor employs low-cost components and simple fabrication processes to lower the overall cost while achieving high sensitivity using a differential detection method. To experimentally demonstrate its limit of detection (LOD), we conducted biosensing experiments with streptavidin and C-reactive protein (CRP). The optical cavity structure was optimized further for better sensitivity and easier fluid control. We utilized the polymer swelling property to fine-tune the optical cavity width, which significantly improved the success rate to produce measurable samples. Four different concentrations of streptavidin were tested in triplicate, and the LOD of the OCB was determined to be 1.35 nM. The OCB also successfully detected three different concentrations of human CRP using biotinylated CRP antibody. The LOD for CRP detection was 377 pM. All measurements were done using a small sample volume of 15 µL within 30 min. By reducing the sensing area, improving the functionalization and passivation processes, and increasing the sample volume, the LOD of the OCB are estimated to be reduced further to the femto-molar range. Overall, the demonstrated capability of the OCB in the present work shows great potential to be used as a promising POC biosensor.

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Label-Free Electrochemical Sensor for Rapid Bacterial Pathogen Detection Using Vancomycin-Modified Highly Branched Polymers

Sensors ◽

10.3390/s21051872 ◽

2021 ◽

Vol 21 (5) ◽

pp. 1872

Author(s):

Holger Schulze ◽

Harry Wilson ◽

Ines Cara ◽

Steven Carter ◽

Edward N. Dyson ◽

...

Keyword(s):

Pathogen Detection ◽

Electrochemical Impedance ◽

Point Of Care ◽

Branched Polymers ◽

Label Free ◽

Conformation Change ◽

Gram Positive ◽

Gram Positive Bacteria ◽

Staphylococcus Carnosus ◽

Label Free Detection

Rapid point of care tests for bacterial infection diagnosis are of great importance to reduce the misuse of antibiotics and burden of antimicrobial resistance. Here, we have successfully combined a new class of non-biological binder molecules with electrochemical impedance spectroscopy (EIS)-based sensor detection for direct, label-free detection of Gram-positive bacteria making use of the specific coil-to-globule conformation change of the vancomycin-modified highly branched polymers immobilized on the surface of gold screen-printed electrodes upon binding to Gram-positive bacteria. Staphylococcus carnosus was detected after just 20 min incubation of the sample solution with the polymer-functionalized electrodes. The polymer conformation change was quantified with two simple 1 min EIS tests before and after incubation with the sample. Tests revealed a concentration dependent signal change within an OD600 range of Staphylococcus carnosus from 0.002 to 0.1 and a clear discrimination between Gram-positive Staphylococcus carnosus and Gram-negative Escherichia coli bacteria. This exhibits a clear advancement in terms of simplified test complexity compared to existing bacteria detection tests. In addition, the polymer-functionalized electrodes showed good storage and operational stability.

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A tandem giant magnetoresistance assay for one-shot quantification of clinically relevant concentrations of N-terminal pro-B-type natriuretic peptide in human blood

Analytical and Bioanalytical Chemistry ◽

10.1007/s00216-021-03227-5 ◽

2021 ◽

Author(s):

Fanda Meng ◽

Weisong Huo ◽

Jie Lian ◽

Lei Zhang ◽

Xizeng Shi ◽

...

Keyword(s):

Detection Limit ◽

Giant Magnetoresistance ◽

Dynamic Range ◽

Point Of Care ◽

Sample Volume ◽

Small Sample ◽

Broad Dynamic Range ◽

Gmr Sensors ◽

Gmr Sensor ◽

Sample Volume Requirement

AbstractWe report a microfluidic sandwich immunoassay constructed around a dual-giant magnetoresistance (GMR) sensor array to quantify the heart failure biomarker NT-proBNP in human plasma at the clinically relevant concentration levels between 15 pg/mL and 40 ng/mL. The broad dynamic range was achieved by differential coating of two identical GMR sensors operated in tandem, and combining two standard curves. The detection limit was determined as 5 pg/mL. The assay, involving 53 plasma samples from patients with different cardiovascular diseases, was validated against the Roche Cobas e411 analyzer. The salient features of this system are its wide concentration range, low detection limit, small sample volume requirement (50 μL), and the need for a short measurement time of 15 min, making it a prospective candidate for practical use in point of care analysis.

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Comparison of DNAzyme activity for the development of an immobilized heme sensor

MRS Advances ◽

10.1557/adv.2017.637 ◽

2018 ◽

Vol 3 (26) ◽

pp. 1491-1496

Author(s):

Natalie Hughes ◽

Nancy Nguyen ◽

Deanna-Kaye Daley ◽

Justin Grennell ◽

Amira Gee ◽

...

Keyword(s):

Self Assembly ◽

Point Of Care ◽

Label Free ◽

Detection Range ◽

Chemical Complexity ◽

Detection Strategy ◽

Detection Approach ◽

Label Free Detection ◽

G Quadruplex ◽

Care Systems

ABSTRACTPoint-of-care systems require highly sensitive, quantitative and selective detection platforms for the real-time multiplexed monitoring of target analytes. To ensure facile development of a sensor, it is preferable for the detection assay to have minimal chemical complexity, contain no wash steps and provide a wide and easily adaptable detection range for multiple targets. Current studies involve label-free detection strategy for relevant clinical molecules such as heme using G-quadruplex based self-assembly. We have explored the measurement of binding and kinetic parameters of various G-quadruplex/heme complexes which are able to self-associate to form a DNAzyme with peroxidase mimicking capabilities and are critical to nucleic acid research. The detection strategy includes immobilizing the G-quadruplex sequences within a polymer matrix to provide a self-assembly based detection approach for heme that could be translated towards other clinically relevant targets.

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Ultrasensitive WSe2 field-effect transistor-based biosensor for label-free detection of cancer in point-of-care applications

2D Materials ◽

10.1088/2053-1583/ac1253 ◽

2021 ◽

Author(s):

Mohammad Mosarof Hossain ◽

Babar Shabbir ◽

Yingjie Wu ◽

Wenzhi Yu ◽

Vaishnavi Krishnamurthi ◽

...

Keyword(s):

Field Effect ◽

Field Effect Transistor ◽

Point Of Care ◽

Label Free ◽

Label Free Detection ◽

Effect Transistor

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Field-Effect Sensors for Virus Detection: From Ebola to SARS-CoV-2 and Plant Viral Enhancers

Frontiers in Plant Science ◽

10.3389/fpls.2020.598103 ◽

2020 ◽

Vol 11 ◽

Cited By ~ 2

Author(s):

Arshak Poghossian ◽

Melanie Jablonski ◽

Denise Molinnus ◽

Christina Wege ◽

Michael J. Schöning

Keyword(s):

Field Effect ◽

Point Of Care ◽

Virus Detection ◽

Fast Response ◽

Plant Viruses ◽

Clinical Samples ◽

Label Free ◽

Label Free Detection ◽

Field Effect Devices ◽

Long Time

Coronavirus disease 2019 (COVID-19) is a novel human infectious disease provoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, no specific vaccines or drugs against COVID-19 are available. Therefore, early diagnosis and treatment are essential in order to slow the virus spread and to contain the disease outbreak. Hence, new diagnostic tests and devices for virus detection in clinical samples that are faster, more accurate and reliable, easier and cost-efficient than existing ones are needed. Due to the small sizes, fast response time, label-free operation without the need for expensive and time-consuming labeling steps, the possibility of real-time and multiplexed measurements, robustness and portability (point-of-care and on-site testing), biosensors based on semiconductor field-effect devices (FEDs) are one of the most attractive platforms for an electrical detection of charged biomolecules and bioparticles by their intrinsic charge. In this review, recent advances and key developments in the field of label-free detection of viruses (including plant viruses) with various types of FEDs are presented. In recent years, however, certain plant viruses have also attracted additional interest for biosensor layouts: Their repetitive protein subunits arranged at nanometric spacing can be employed for coupling functional molecules. If used as adapters on sensor chip surfaces, they allow an efficient immobilization of analyte-specific recognition and detector elements such as antibodies and enzymes at highest surface densities. The display on plant viral bionanoparticles may also lead to long-time stabilization of sensor molecules upon repeated uses and has the potential to increase sensor performance substantially, compared to conventional layouts. This has been demonstrated in different proof-of-concept biosensor devices. Therefore, richly available plant viral particles, non-pathogenic for animals or humans, might gain novel importance if applied in receptor layers of FEDs. These perspectives are explained and discussed with regard to future detection strategies for COVID-19 and related viral diseases.

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Multitarget, quantitative nanoplasmonic electrical field-enhanced resonating device (NE2RD) for diagnostics

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1510824112 ◽

2015 ◽

Vol 112 (32) ◽

pp. E4354-E4363 ◽

Cited By ~ 44

Author(s):

Fatih Inci ◽

Chiara Filippini ◽

Murat Baday ◽

Mehmet Ozgun Ozen ◽

Semih Calamak ◽

...

Keyword(s):

Dynamic Range ◽

Point Of Care ◽

Medical Diagnostics ◽

Clinical Samples ◽

Label Free ◽

Protein Biomarkers ◽

Electrical Field ◽

Color Changes ◽

Sensing Platform ◽

Broad Dynamic Range

Recent advances in biosensing technologies present great potential for medical diagnostics, thus improving clinical decisions. However, creating a label-free general sensing platform capable of detecting multiple biotargets in various clinical specimens over a wide dynamic range, without lengthy sample-processing steps, remains a considerable challenge. In practice, these barriers prevent broad applications in clinics and at patients’ homes. Here, we demonstrate the nanoplasmonic electrical field-enhanced resonating device (NE2RD), which addresses all these impediments on a single platform. The NE2RD employs an immunodetection assay to capture biotargets, and precisely measures spectral color changes by their wavelength and extinction intensity shifts in nanoparticles without prior sample labeling or preprocessing. We present through multiple examples, a label-free, quantitative, portable, multitarget platform by rapidly detecting various protein biomarkers, drugs, protein allergens, bacteria, eukaryotic cells, and distinct viruses. The linear dynamic range of NE2RD is five orders of magnitude broader than ELISA, with a sensitivity down to 400 fg/mL This range and sensitivity are achieved by self-assembling gold nanoparticles to generate hot spots on a 3D-oriented substrate for ultrasensitive measurements. We demonstrate that this precise platform handles multiple clinical samples such as whole blood, serum, and saliva without sample preprocessing under diverse conditions of temperature, pH, and ionic strength. The NE2RD’s broad dynamic range, detection limit, and portability integrated with a disposable fluidic chip have broad applications, potentially enabling the transition toward precision medicine at the point-of-care or primary care settings and at patients’ homes.

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Electrochemical DNA Detection Methods to Measure Circulating Tumour DNA for Enhanced Diagnosis and Monitoring of Cancer

Proceedings ◽

10.3390/iecb2020-07067 ◽

2020 ◽

Vol 60 (1) ◽

pp. 15

Author(s):

Bukola Attoye ◽

Matthew Baker ◽

Chantevy Pou ◽

Fiona Thomson ◽

Damion K. Corrigan

Keyword(s):

Point Of Care ◽

Low Cost ◽

Detection Methods ◽

Clinical Samples ◽

Label Free ◽

Ambient Conditions ◽

Liquid Biopsies ◽

Current Time ◽

Electrochemical Approach ◽

Label Free Detection

Liquid biopsies are becoming increasingly important as a potential replacement for existing biopsy procedures which can be invasive, painful and compromised by tumour heterogeneity. This paper reports a simple electrochemical approach tailored towards point-of-care cancer detection and treatment monitoring from biofluids using a label-free detection strategy. The mutations under test were the KRAS G12D and G13D mutations, which are both important in the development and progression of many human cancers and which have a presence that correlates with poor outcomes. These common circulating tumour markers were investigated in clinical samples and amplified by standard and specialist PCR methodologies for subsequent electrochemical detection. Following pre-treatment of the sensor to present a clean surface, DNA probes developed specifically for detection of the KRAS G12D and G13D mutations were immobilized onto low-cost carbon electrodes using diazonium chemistry and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride/N-hydroxysuccinimide coupling. Following the functionalisation of the sensor, it was possible to sensitively and specifically detect a mutant KRAS G13D PCR product against a background of wild-type KRAS DNA from the representative cancer sample. Our findings give rise to the basis of a simple and very low-cost system for measuring ctDNA biomarkers in patient samples. The current time to result of the system was 3.5 h with considerable scope for optimisation, and it already compares favourably to the UK National Health Service biopsy service where patients can wait weeks for their result. This paper reports the technical developments we made in the production of consistent carbon surfaces for functionalisation, assay performance data for KRAS G13D and detection of PCR amplicons under ambient conditions.

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Super-Nernstian ion sensitive field-effect transistor exploiting charge screening in WSe2/MoS2 heterostructure

npj 2D Materials and Applications ◽

10.1038/s41699-021-00273-6 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Sooraj Sanjay ◽

Mainul Hossain ◽

Ankit Rao ◽

Navakanta Bhat

Keyword(s):

Field Effect ◽

Field Effect Transistors ◽

Point Of Care ◽

Low Cost ◽

Ph Sensor ◽

Detection Sensitivity ◽

Label Free ◽

Back Gate ◽

Dielectric Thickness ◽

Label Free Detection

AbstractIon-sensitive field-effect transistors (ISFETs) have gained a lot of attention in recent times as compact, low-cost biosensors with fast response time and label-free detection. Dual gate ISFETs have been shown to enhance detection sensitivity beyond the Nernst limit of 59 mV pH−1 when the back gate dielectric is much thicker than the top dielectric. However, the thicker back-dielectric limits its application for ultrascaled point-of-care devices. In this work, we introduce and demonstrate a pH sensor, with WSe2(top)/MoS2(bottom) heterostructure based double gated ISFET. The proposed device is capable of surpassing the Nernst detection limit and uses thin high-k hafnium oxide as the gate oxide. The 2D atomic layered structure, combined with nanometer-thick top and bottom oxides, offers excellent scalability and linear response with a maximum sensitivity of 362 mV pH−1. We have also used technology computer-aided (TCAD) simulations to elucidate the underlying physics, namely back gate electric field screening through channel and interface charges due to the heterointerface. The proposed mechanism is independent of the dielectric thickness that makes miniaturization of these devices easier. We also demonstrate super-Nernstian behavior with the flipped MoS2(top)/WSe2(bottom) heterostructure ISFET. The results open up a new pathway of 2D heterostructure engineering as an excellent option for enhancing ISFET sensitivity beyond the Nernst limit, for the next-generation of label-free biosensors for single-molecular detection and point-of-care diagnostics.

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