Silicon Photonic Biosensors Using Label-Free Detection

Thanks to advanced semiconductor microfabrication technology, chip-scale integration and miniaturization of lab-on-a-chip components, silicon-based optical biosensors have made significant progress for the purpose of point-of-care diagnosis. In this review, we provide an overview of the state-of-the-art in evanescent field biosensing technologies including interferometer, microcavity, photonic crystal, and Bragg grating waveguide-based sensors. Their sensing mechanisms and sensor performances, as well as real biomarkers for label-free detection, are exhibited and compared. We also review the development of chip-level integration for lab-on-a-chip photonic sensing platforms, which consist of the optical sensing device, flow delivery system, optical input and readout equipment. At last, some advanced system-level complementary metal-oxide semiconductor (CMOS) chip packaging examples are presented, indicating the commercialization potential for the low cost, high yield, portable biosensing platform leveraging CMOS processes.

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Silicon Photonic Biosensors Using Label-Free Detection

10.20944/preprints201809.0150.v1 ◽

2018 ◽

Author(s):

Enxiao Luan ◽

Hossam Shoman ◽

Daniel M. Ratner ◽

Karen C. Cheung ◽

Lukas Chrostowski

Keyword(s):

Point Of Care ◽

Low Cost ◽

Lab On A Chip ◽

System Level ◽

High Yield ◽

Label Free ◽

Label Free Detection ◽

Microfabrication Technology ◽

Scale Integration ◽

Silicon Based

Thanks to advanced semiconductor microfabrication technology, chip-scale integration and miniaturization of lab-on-a-chip components, silicon-based optical biosensors have made significant progress for the purpose of point-of-care diagnosis. In this review, we provide an overview of the state-of-the-art in evanescent field biosensing technologies including interferometer, microcavity, photonic crystal, and Bragg grating waveguide-based sensors. Their sensing mechanisms and sensor performances, as well as real biomarkers for label-free detection, are exhibited and compared. We also review the development of chip-level integration for lab-on-a-chip photonic sensing platforms, which consist of the optical sensing device, flow delivery system, optical input and readout equipment. At last, some advanced system-level CMOS-chip packaging examples are presented, indicating the commercialization potential for the low cost, high yield, portable biosensing platform leveraging CMOS processes.

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Silicon Photonic Biosensors Using Label-Free Detection

10.20944/preprints201809.0150.v2 ◽

2018 ◽

Author(s):

Enxiao Luan ◽

Hossam Shoman ◽

Daniel M. Ratner ◽

Karen C. Cheung ◽

Lukas Chrostowski

Keyword(s):

Point Of Care ◽

Low Cost ◽

Lab On A Chip ◽

System Level ◽

High Yield ◽

Label Free ◽

Label Free Detection ◽

Microfabrication Technology ◽

Scale Integration ◽

Silicon Based

Thanks to advanced semiconductor microfabrication technology, chip-scale integration and miniaturization of lab-on-a-chip components, silicon-based optical biosensors have made significant progress for the purpose of point-of-care diagnosis. In this review, we provide an overview of the state-of-the-art in evanescent field biosensing technologies including interferometer, microcavity, photonic crystal, and Bragg grating waveguide-based sensors. Their sensing mechanisms and sensor performances, as well as real biomarkers for label-free detection, are exhibited and compared. We also review the development of chip-level integration for lab-on-a-chip photonic sensing platforms, which consist of the optical sensing device, flow delivery system, optical input and readout equipment. At last, some advanced system-level CMOS-chip packaging examples are presented, indicating the commercialization potential for the low cost, high yield, portable biosensing platform leveraging CMOS processes.

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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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Amorphous Silicon Thin Film Transistor Biosensing System

MRS Proceedings ◽

10.1557/opl.2013.81 ◽

2013 ◽

Vol 1530 ◽

Author(s):

Hanbin Ma ◽

Ben Miller ◽

Sungsik Lee ◽

Arman Ahnood ◽

Marius Bauza ◽

...

Keyword(s):

Thin Film ◽

Amorphous Silicon ◽

High Reliability ◽

Low Cost ◽

Thin Film Transistor ◽

Ring Oscillator ◽

Oxide Semiconductor ◽

Label Free ◽

Silicon Thin Film ◽

Label Free Detection

ABSTRACTElectronic systems are a very good platform for sensing biological signals for fast point-of-care diagnostics or threat detection. One of the solutions is the lab-on-a-chip integrated circuit (IC), which is low cost and high reliability, offering the possibility for label-free detection. In recent years, similar integrated biosensors based on the conventional complementary metal oxide semiconductor (CMOS) technology have been reported. However, post-fabrication processes are essential for all classes of CMOS biochips, requiring biocompatible electrode deposition and circuit encapsulation.In this work, we present an amorphous silicon (a-Si) thin film transistor (TFT) array based sensing approach, which greatly simplifies the fabrication procedures and even decreases the cost of the biosensor. The device contains several identical sensor pixels with amplifiers to boost the sensitivity. Ring oscillator and logic circuits are also integrated to achieve different measurement methodologies, including electro-analytical methods such as amperometric and cyclic voltammetric modes. The system also supports different operational modes. For example, depending on the required detection arrangement, a sample droplet could be placed on the sensing pads or the device could be immersed into the sample solution for real time in-situ measurement. The entire system is designed and fabricated using a low temperature TFT process that is compatible to plastic substrates. No additional processing is required prior to biological measurement. A Cr/Au double layer is used for the biological-electronic interface. The success of the TFT-based system used in this work will open new avenues for flexible label-free or low-cost disposable biosensors.

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Design of Fully Integrated Impedimetric CMOS Biosensor for DNA Detection

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.925.524 ◽

2014 ◽

Vol 925 ◽

pp. 524-528

Author(s):

Vinny Lam Siu Fan ◽

Yusmeeraz Binti Yusof

Keyword(s):

Dynamic Range ◽

Low Cost ◽

Complementary Metal Oxide Semiconductor ◽

Cmos Technology ◽

High Gain ◽

Oxide Semiconductor ◽

Impedance Change ◽

Readout Circuit ◽

Label Free ◽

Fully Integrated

This paper described a label-free and fully integrated impedimetric biosensor using standard Complementary Metal Oxide Semiconductor (CMOS) technology to measure both capacitance and resistance of the electrode-electrolyte interface. Conventional impedance biosensors usually use bulky and expensive instruments to monitor the impedance change. This paper demonstrates a low power, high gain and low cost impedance readout circuit design for detecting the biomolecular interactions of deoxyribonucleic acid (DNA) strands at the electrode surface. The proposed biosensor circuit is composed of a transimpedance amplifier (TIA) with two quadrature phase mixers and finally integrated with 5μm x 5μm microelectrode based on 0.18μm Silterra CMOS technology process with 1.8V supply. The output value of the readout circuit is used to estimate the amplitude and phase of the measured admittance. The developed TIA can achieve a gain of 88.6dB up to a frequency of 50MHz. It also has very good linearity up to 2.7mA and the overall dynamic range is approximately 90dB.

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Complementary Metal-Oxide Semiconductor (CMOS) Image Sensor: An Insight as a Point-of-Care Label-Free Immunosensor

Analytical Sciences ◽

10.2116/analsci.26.1215 ◽

2010 ◽

Vol 26 (12) ◽

pp. 1215-1217 ◽

Cited By ~ 9

Author(s):

Karthikeyan KANDASAMY ◽

Mohana MARIMUTHU ◽

Gun Yong SUNG ◽

Chang Geun AHN ◽

Sanghyo KIM

Keyword(s):

Metal Oxide ◽

Point Of Care ◽

Complementary Metal Oxide Semiconductor ◽

Cmos Image Sensor ◽

Image Sensor ◽

Metal Oxide Semiconductor ◽

Oxide Semiconductor ◽

Label Free

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Integrated microfluidic chip with nanobiosensor for rapid and label-free detection of a specific gene

Analytical Methods ◽

10.1039/c7ay00950j ◽

2017 ◽

Vol 9 (24) ◽

pp. 3619-3625 ◽

Cited By ~ 1

Author(s):

Congxiao Zhang ◽

Xuefei Lv ◽

Saeed Yasmeen ◽

Hong Qing ◽

Yulin Deng

Keyword(s):

Food Safety ◽

Point Of Care ◽

Low Cost ◽

Specific Gene ◽

Label Free ◽

Biomolecular Detection ◽

Detection Techniques ◽

Label Free Detection ◽

Rapid Tests ◽

Point Of Care Tests

Biomolecular detection techniques are tending to develop in terms of miniaturization, automation, rapidity, sensitivity and low cost, and these techniques are urgently needed as “point of care tests” or “rapid tests” in clinical diagnosis, environmental monitoring and food safety.

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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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