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

Proceedings ◽  
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.

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

2020 ◽  
Vol 11 ◽  
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.

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

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.

scholarly journals An uncomplicated electrochemical sensor combining a perfluorocarbon SAM and ACE2 as the bio-recognition element to sensitively and specifically detect SARS-CoV-2 in complex samples.

2020 ◽  
Author(s):  
Vincent Vezza ◽  
Adrian Butterworth ◽  
Perrine Lasserre ◽  
Ewen O Blair ◽  
Alexander MacDonald ◽  
...  
Keyword(s):  
Specific Binding ◽  
Low Cost ◽  
Diagnostic Testing ◽  
Economic Effects ◽  
Spike Protein ◽  
Clinical Samples ◽  
Label Free ◽  
Ambient Conditions ◽  
Electrochemical Assay ◽  
Recognition Element

Emerging in late 2019, the SARS-CoV-2 virus has had a devastating health and economic effects around the world forcing governments to enact restrictions on day to day life, resulting in severe economic and social disruption. The virus has stimulated new research in the fields of drug development, vaccinology and diagnostic testing. Here we present the basis for a simple, mass manufacturable saliva based electrochemical assay for the SARS-CoV-2 virus acheived through adsorption of the Angiotsnsin Converting Enzyme 2 (ACE2) into thiolated amphiphobic prefluoro monolayer assemled on a gold sensor surface. Following sensor preparation, it is possible to measure specific binding of recombinant spike protein and discriminate positive and negative samples of inactivated SARS-CoV-2 following 30 minutes incubation under ambient conditions. Representative calculations of limits of detection are made for recombinant spike protein (1.68 ng/ml) and inactivated virus (37.8 dC/mL). The assay as presented ultimately shows discrimination between positive and negative inactivated SARS-CoV-2 samples originating from clinical molecular standards kit intended for clinical and biomedical assay validation, and which is designed to mimic clinical samples through presence of cells and proteins in the sample medium. The simple design of the label free measurement and the selection of reagents involved means the assay has clear potential for transfer onto mass producible units such as screen-printed electrodes similar to glucose-format test strips, to enable widespread, low cost and rapid testing for SARS-CoV-2 in the general population

scholarly journals An uncomplicated electrochemical sensor combining a perfluorocarbon SAM and ACE2 as the bio-recognition element to sensitively and specifically detect SARS-CoV-2 in complex samples.

2020 ◽  
Author(s):  
Vincent Vezza ◽  
Adrian Butterworth ◽  
Perrine Lasserre ◽  
Ewen O Blair ◽  
Alexander MacDonald ◽  
...  
Keyword(s):  
Specific Binding ◽  
Low Cost ◽  
Diagnostic Testing ◽  
Economic Effects ◽  
Spike Protein ◽  
Clinical Samples ◽  
Label Free ◽  
Ambient Conditions ◽  
Electrochemical Assay ◽  
Recognition Element

Emerging in late 2019, the SARS-CoV-2 virus has had a devastating health and economic effects around the world forcing governments to enact restrictions on day to day life, resulting in severe economic and social disruption. The virus has stimulated new research in the fields of drug development, vaccinology and diagnostic testing. Here we present the basis for a simple, mass manufacturable saliva based electrochemical assay for the SARS-CoV-2 virus acheived through adsorption of the Angiotsnsin Converting Enzyme 2 (ACE2) into thiolated amphiphobic prefluoro monolayer assemled on a gold sensor surface. Following sensor preparation, it is possible to measure specific binding of recombinant spike protein and discriminate positive and negative samples of inactivated SARS-CoV-2 following 30 minutes incubation under ambient conditions. Representative calculations of limits of detection are made for recombinant spike protein (1.68 ng/ml) and inactivated virus (37.8 dC/mL). The assay as presented ultimately shows discrimination between positive and negative inactivated SARS-CoV-2 samples originating from clinical molecular standards kit intended for clinical and biomedical assay validation, and which is designed to mimic clinical samples through presence of cells and proteins in the sample medium. The simple design of the label free measurement and the selection of reagents involved means the assay has clear potential for transfer onto mass producible units such as screen-printed electrodes similar to glucose-format test strips, to enable widespread, low cost and rapid testing for SARS-CoV-2 in the general population

scholarly journals Silicon Photonic Biosensors Using Label-Free Detection

Sensors ◽  
2018 ◽  
Vol 18 (10) ◽  
pp. 3519 ◽  
Author(s):  
Enxiao Luan ◽  
Hossam Shoman ◽  
Daniel Ratner ◽  
Karen Cheung ◽  
Lukas Chrostowski
Keyword(s):  
Point Of Care ◽  
Low Cost ◽  
Lab On A Chip ◽  
Complementary Metal Oxide Semiconductor ◽  
Oxide Semiconductor ◽  
System Level ◽  
High Yield ◽  
Label Free ◽  
Label Free Detection ◽  
Microfabrication Technology

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.

scholarly journals Optimisation of an Electrochemical DNA Sensor for Measuring KRAS G12D and G13D Point Mutations in Different Tumour Types

Biosensors ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 42
Author(s):  
Bukola Attoye ◽  
Matthew J. Baker ◽  
Fiona Thomson ◽  
Chantevy Pou ◽  
Damion K. Corrigan
Keyword(s):  
Electrochemical Detection ◽  
Low Cost ◽  
Carbon Surface ◽  
Electrochemical Technique ◽  
Dna Sensor ◽  
Liquid Biopsies ◽  
Detection Scheme ◽  
Current Time ◽  
Label Free Detection ◽  
Pre Treatment

Circulating tumour DNA (ctDNA) is widely used in liquid biopsies due to having a presence in the blood that is typically in proportion to the stage of the cancer and because it may present a quick and practical method of capturing tumour heterogeneity. This paper outlines a simple electrochemical technique adapted towards point-of-care cancer detection and treatment monitoring from biofluids using a label-free detection strategy. The mutations used for analysis were the KRAS G12D and G13D mutations, which are both important in the initiation, progression and drug resistance of many human cancers, leading to a high mortality rate. A low-cost DNA sensor was developed to specifically investigate these common circulating tumour markers. Initially, we report on some developments made in carbon surface pre-treatment and the electrochemical detection scheme which ensure the most sensitive measurement technique is employed. Following pre-treatment of the sensor to ensure homogeneity, DNA probes developed specifically for detection of the KRAS G12D and G13D mutations were immobilized onto low-cost screen printed carbon electrodes using diazonium chemistry and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride/N-hydroxysuccinimide coupling. Prior to electrochemical detection, the sensor was functionalised with target DNA amplified by standard and specialist PCR methodologies (6.3% increase). Assay development steps and DNA detection experiments were performed using standard voltammetry techniques. Sensitivity (as low as 0.58 ng/μL) and specificity (>300%) was achieved by detecting mutant KRAS G13D PCR amplicons against a background of wild-type KRAS DNA from the representative cancer sample and 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 receive results from the system was 3.5 h with appreciable scope for optimisation, thus far comparing favourably to the UK National Health Service biopsy service where patients can wait for weeks for biopsy results.

scholarly journals Graphene Quantum Dot-Based Electrochemical Immunosensors for Biomedical Applications

Materials ◽  
2019 ◽  
Vol 13 (1) ◽  
pp. 96 ◽  
Author(s):  
Bhargav D. Mansuriya ◽  
Zeynep Altintas
Keyword(s):  
Electrochemical Sensors ◽  
Point Of Care ◽  
Low Cost ◽  
Graphene Quantum Dots ◽  
Clinical Samples ◽  
Label Free ◽  
Electrochemical Immunosensors ◽  
Biomedical Diagnosis ◽  
Electrochemical Immunosensing ◽  
Distinct Features

In the area of biomedicine, research for designing electrochemical sensors has evolved over the past decade, since it is crucial to selectively quantify biomarkers or pathogens in clinical samples for the efficacious diagnosis and/or treatment of various diseases. To fulfil the demand of rapid, specific, economic, and easy detection of such biomolecules in ultralow amounts, numerous nanomaterials have been explored to effectively enhance the sensitivity, selectivity, and reproducibility of immunosensors. Graphene quantum dots (GQDs) have garnered tremendous attention in immunosensor development, owing to their special attributes such as large surface area, excellent biocompatibility, quantum confinement, edge effects, and abundant sites for chemical modification. Besides these distinct features, GQDs acquire peroxidase (POD)-mimicking electro-catalytic activity, and hence, they can replace horseradish peroxidase (HRP)-based systems to conduct facile, quick, and inexpensive label-free immunoassays. The chief motive of this review article is to summarize and focus on the recent advances in GQD-based electrochemical immunosensors for the early and rapid detection of cancer, cardiovascular disorders, and pathogenic diseases. Moreover, the underlying principles of electrochemical immunosensing techniques are also highlighted. These GQD immunosensors are ubiquitous in biomedical diagnosis and conducive for miniaturization, encouraging low-cost disease diagnostics in developing nations using point-of-care testing (POCT) and similar allusive techniques.

scholarly journals Silicon Photonic Biosensors Using Label-Free Detection

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.

scholarly journals Silicon Photonic Biosensors Using Label-Free Detection

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.

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

2017 ◽  
Vol 9 (24) ◽  
pp. 3619-3625 ◽  
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.

Sign in / Sign up

Export Citation Format

Share Document