scholarly journals Silicon Photonic Biosensors Using Label-Free Detection

Author(s):  
Enxiao Luan ◽  
Hossam Shoman ◽  
Daniel M. Ratner ◽  
Karen C. Cheung ◽  
Lukas Chrostowski

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.

Author(s):  
Enxiao Luan ◽  
Hossam Shoman ◽  
Daniel M. Ratner ◽  
Karen C. Cheung ◽  
Lukas Chrostowski

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.


Sensors ◽  
2018 ◽  
Vol 18 (10) ◽  
pp. 3519 ◽  
Author(s):  
Enxiao Luan ◽  
Hossam Shoman ◽  
Daniel Ratner ◽  
Karen Cheung ◽  
Lukas Chrostowski

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.


Proceedings ◽  
2020 ◽  
Vol 60 (1) ◽  
pp. 15
Author(s):  
Bukola Attoye ◽  
Matthew Baker ◽  
Chantevy Pou ◽  
Fiona Thomson ◽  
Damion K. Corrigan

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.


2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Sooraj Sanjay ◽  
Mainul Hossain ◽  
Ankit Rao ◽  
Navakanta Bhat

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.


2017 ◽  
Vol 9 (24) ◽  
pp. 3619-3625 ◽  
Author(s):  
Congxiao Zhang ◽  
Xuefei Lv ◽  
Saeed Yasmeen ◽  
Hong Qing ◽  
Yulin Deng

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.


Biosensors ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 4
Author(s):  
Donggee Rho ◽  
Seunghyun Kim

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.


Sensors ◽  
2021 ◽  
Vol 21 (5) ◽  
pp. 1872
Author(s):  
Holger Schulze ◽  
Harry Wilson ◽  
Ines Cara ◽  
Steven Carter ◽  
Edward N. Dyson ◽  
...  

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.


Author(s):  
Antonia Perju ◽  
Nongnoot Wongkaew

AbstractLateral flow assays (LFAs) are the best-performing and best-known point-of-care tests worldwide. Over the last decade, they have experienced an increasing interest by researchers towards improving their analytical performance while maintaining their robust assay platform. Commercially, visual and optical detection strategies dominate, but it is especially the research on integrating electrochemical (EC) approaches that may have a chance to significantly improve an LFA’s performance that is needed in order to detect analytes reliably at lower concentrations than currently possible. In fact, EC-LFAs offer advantages in terms of quantitative determination, low-cost, high sensitivity, and even simple, label-free strategies. Here, the various configurations of EC-LFAs published are summarized and critically evaluated. In short, most of them rely on applying conventional transducers, e.g., screen-printed electrode, to ensure reliability of the assay, and additional advances are afforded by the beneficial features of nanomaterials. It is predicted that these will be further implemented in EC-LFAs as high-performance transducers. Considering the low cost of point-of-care devices, it becomes even more important to also identify strategies that efficiently integrate nanomaterials into EC-LFAs in a high-throughput manner while maintaining their favorable analytical performance.


MRS Advances ◽  
2018 ◽  
Vol 3 (26) ◽  
pp. 1491-1496
Author(s):  
Natalie Hughes ◽  
Nancy Nguyen ◽  
Deanna-Kaye Daley ◽  
Justin Grennell ◽  
Amira Gee ◽  
...  

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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