scholarly journals Label-free DNA biosensing by topological light confinement

Nanophotonics ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Gianluigi Zito ◽  
Gennaro Sanità ◽  
Bryan Guilcapi Alulema ◽  
Sofía N. Lara Yépez ◽  
Vittorino Lanzio ◽  
...  
Keyword(s):  
Single Molecule ◽  
Bound States ◽  
Production Control ◽  
Point Of Care ◽  
Low Cost ◽  
Label Free ◽  
Large Area ◽  
Light Confinement ◽  
Binding Event ◽  
The Continuum

Abstract Large-area and transparent all-dielectric metasurfaces sustaining photonic bound states in the continuum (BICs) provide a set of fundamental advantages for ultrasensitive biosensing. BICs bridge the gap of large effective mode volume with large experimental quality factor. Relying on the transduction mechanism of reactive sensing principle, herein, we first numerically study the potential of subwavelength confinement driven by topological decoupling from free space radiation for BIC-based biosensing. Then, we experimentally combine this capability with minimal and low-cost optical setup, applying the devised quasi-BIC resonator for PNA/DNA selective biosensing with real-time monitoring of the binding event. A sensitivity of 20 molecules per micron squared is achieved, i.e. ≃0.01 pg. Further enhancement can easily be envisaged, pointing out the possibility of single-molecule regime. This work aims at a precise and ultrasensitive approach for developing low-cost point-of-care tools suitable for routine disease prescreening analyses in laboratory, also adaptable to industrial production control.

scholarly journals Ultra-low HIV-1 p24 detection limits with a bioelectronic sensor

2019 ◽  
Vol 412 (4) ◽  
pp. 811-818 ◽  
Author(s):  
Eleonora Macchia ◽  
Lucia Sarcina ◽  
Rosaria Anna Picca ◽  
Kyriaki Manoli ◽  
Cinzia Di Franco ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Single Molecule ◽  
Limit Of Detection ◽  
Point Of Care ◽  
Low Cost ◽  
Wide Field ◽  
Label Free ◽  
Limit Of Quantification ◽  
Great Relevance ◽  
Hiv 1

AbstractEarly diagnosis of the infection caused by human immunodeficiency virus type-1 (HIV-1) is vital to achieve efficient therapeutic treatment and limit the disease spreading when the viremia is at its highest level. To this end, a point-of-care HIV-1 detection carried out with label-free, low-cost, and ultra-sensitive screening technologies would be of great relevance. Herein, a label-free single molecule detection of HIV-1 p24 capsid protein with a large (wide-field) single-molecule transistor (SiMoT) sensor is proposed. The system is based on an electrolyte-gated field-effect transistor whose gate is bio-functionalized with the antibody against the HIV-1 p24 capsid protein. The device exhibits a limit of detection of a single protein and a limit of quantification in the 10 molecule range. This study paves the way for a low-cost technology that can quantify, with single-molecule precision, the transition of a biological organism from being “healthy” to being “diseased” by tracking a target biomarker. This can open to the possibility of performing the earliest possible diagnosis.

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

Biosensors ◽  
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.

scholarly journals Integrating high-performing electrochemical transducers in lateral flow assay

2021 ◽  
Author(s):  
Antonia Perju ◽  
Nongnoot Wongkaew
Keyword(s):  
High Performance ◽  
Point Of Care ◽  
Low Cost ◽  
High Sensitivity ◽  
Lateral Flow ◽  
Analytical Performance ◽  
Label Free ◽  
High Performing ◽  
Lateral Flow Assays ◽  
Electrochemical Transducers

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.

scholarly journals Beating the reaction limits of biosensor sensitivity with dynamic tracking of single binding events

2019 ◽  
Vol 116 (10) ◽  
pp. 4129-4134 ◽  
Author(s):  
Derin Sevenler ◽  
Jacob Trueb ◽  
M. Selim Ünlü
Keyword(s):  
Single Molecule ◽  
Limit Of Detection ◽  
Solid Phase ◽  
Large Area ◽  
Kinetic Assay ◽  
Synthetic Dna ◽  
Dynamic Tracking ◽  
Binding Event ◽  
Endpoint Assay ◽  
Phase Sensor

The clinical need for ultrasensitive molecular analysis has motivated the development of several endpoint-assay technologies capable of single-molecule readout. These endpoint assays are now primarily limited by the affinity and specificity of the molecular-recognition agents for the analyte of interest. In contrast, a kinetic assay with single-molecule readout could distinguish between low-abundance, high-affinity (specific analyte) and high-abundance, low-affinity (nonspecific background) binding by measuring the duration of individual binding events at equilibrium. Here, we describe such a kinetic assay, in which individual binding events are detected and monitored during sample incubation. This method uses plasmonic gold nanorods and interferometric reflectance imaging to detect thousands of individual binding events across a multiplex solid-phase sensor with a large area approaching that of leading bead-based endpoint-assay technologies. A dynamic tracking procedure is used to measure the duration of each event. From this, the total rates of binding and debinding as well as the distribution of binding-event durations are determined. We observe a limit of detection of 19 fM for a proof-of-concept synthetic DNA analyte in a 12-plex assay format.

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 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 A ClyA nanopore tweezer for analysis of functional states of protein-ligand interactions

2019 ◽  
Author(s):  
Xin Li ◽  
Kuohao Lee ◽  
Jianhan Chen ◽  
Min Chen
Keyword(s):  
Single Molecule ◽  
Conformational Changes ◽  
Bound States ◽  
Conformational Dynamics ◽  
Electrical Current ◽  
Label Free ◽  
Protein Motions ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Molecular Tweezer

AbstractConformational changes of proteins are essential to their functions. Yet it remains challenging to measure the amplitudes and timescales of protein motions. Here we show that the ClyA nanopore can be used as a molecular tweezer to trap a single maltose-binding protein (MBP) within its lumen, which allows conformation changes to be monitored as electrical current fluctuations in real time. The current measurements revealed three distinct ligand-bound states for MBP in the presence of reducing saccharides. Our biochemical and kinetic analysis reveal that these three states represented MBP bound to different isomers of reducing sugars. These findings shed light on the mechanism of substrate recognition by MBP and illustrate that the nanopore tweezer is a powerful, label-free, single-molecule approach for studying protein conformational dynamics under functional conditions.

scholarly journals Imaging-based spectrometer-less optofluidic biosensors based on dielectric metasurfaces for detecting extracellular vesicles

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yasaman Jahani ◽  
Eduardo R. Arvelo ◽  
Filiz Yesilkoy ◽  
Kirill Koshelev ◽  
Chiara Cianciaruso ◽  
...  
Keyword(s):  
Real Time ◽  
Extracellular Vesicles ◽  
Bound States ◽  
Point Of Care ◽  
Complementary Metal Oxide Semiconductor ◽  
Spectral Shift ◽  
Processing Technique ◽  
Oxide Semiconductor ◽  
Linear Estimator ◽  
Large Area

AbstractBiosensors are indispensable tools for public, global, and personalized healthcare as they provide tests that can be used from early disease detection and treatment monitoring to preventing pandemics. We introduce single-wavelength imaging biosensors capable of reconstructing spectral shift information induced by biomarkers dynamically using an advanced data processing technique based on an optimal linear estimator. Our method achieves superior sensitivity without wavelength scanning or spectroscopy instruments. We engineered diatomic dielectric metasurfaces supporting bound states in the continuum that allows high-quality resonances with accessible near-fields by in-plane symmetry breaking. The large-area metasurface chips are configured as microarrays and integrated with microfluidics on an imaging platform for real-time detection of breast cancer extracellular vesicles encompassing exosomes. The optofluidic system has high sensing performance with nearly 70 1/RIU figure-of-merit enabling detection of on average 0.41 nanoparticle/µm2 and real-time measurements of extracellular vesicles binding from down to 204 femtomolar solutions. Our biosensors provide the robustness of spectrometric approaches while substituting complex instrumentation with a single-wavelength light source and a complementary-metal-oxide-semiconductor camera, paving the way toward miniaturized devices for point-of-care diagnostics.

scholarly journals Portable tumor biosensing of serum by plasmonic biochips in combination with nanoimprint and microfluidics

Nanophotonics ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 307-316 ◽  
Author(s):  
Jianyang Zhou ◽  
Feng Tao ◽  
Jinfeng Zhu ◽  
Shaowei Lin ◽  
Zhengying Wang ◽  
...  
Keyword(s):  
Nanoimprint Lithography ◽  
Clinical Medicine ◽  
Point Of Care ◽  
Low Cost ◽  
Human Tumor ◽  
High Sensitivity ◽  
Visible Range ◽  
Label Free ◽  
Portable Detection ◽  
Clinical Experiments

AbstractPlasmonic sensing has a great potential in the portable detection of human tumor markers, among which the carcinoembryonic antigen (CEA) is one of the most widely used in clinical medicine. Traditional plasmonic and non-plasmonic methods for CEA biosensing are still not suitable for the fast developing era of Internet of things. In this study, we build up a cost-effective plasmonic immunochip platform for rapid portable detection of CEA by combining soft nanoimprint lithography, microfluidics, antibody functionalization, and mobile fiber spectrometry. The plasmonic gold nanocave array enables stable surface functionality, high sensitivity, and simple reflective measuring configuration in the visible range. The rapid quantitative CEA sensing is implemented by a label-free scheme, and the detection capability for the concentration of less than 5 ng/ml is achieved in clinical experiments, which is much lower than the CEA cancer diagnosis threshold of 20 ng/ml and absolutely sufficient for medical applications. Clinical tests of the chip on detecting human serums demonstrate good agreement with conventional medical examinations and great advantages on simultaneous multichannel detections for high-throughput and multi-marker biosensing. Our platform provides promising opportunities on low-cost and compact medical devices and systems with rapid and sensitive tumor detection for point-of-care diagnosis and mobile healthcare.

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