scholarly journals The potential of SERS as an AST methodology in clinical settings

Nanophotonics ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ota Samek ◽  
Silvie Bernatová ◽  
Fadi Dohnal

Abstract The ability to identify and characterize microorganisms from tiny sample volumes in a rapid and reliable way is the first and crucial step in the diagnostics of microbial infections. Ideal analytical techniques would require minimal and low-cost sample preparation, permit automatic analysis of many serial samples, and allow rapid classification of present microorganisms against a stable database. Current practice, however, is far from this ideal; a typical analytical procedure might require a few days. Delayed laboratory results might lead, for example, to progress/spread of the infection, more serious condition of the patient, even death, prescription of inappropriate antibiotics that could be ineffective against causative agents and may as well contribute to the emerging problem of drug resistance in microorganisms. Several studies confirmed that surface enhanced Raman scattering (SERS) is capable of a rapid identification and discrimination of biological samples including medically relevant bacteria. A typical spectrum contains a wealth of information indicative of the cellular content of nucleic acids, purine bases, proteins, carbohydrates, and lipids. Such a spectrum functions as a cellular ‘fingerprint’ and serves as a sensitive indicator of the physiological state of the cell which in turn enables to differentiate cell types, actual physiological states, nutrient conditions, and phenotype changes. Consequently, the focus of this review is on the SERS spectra of bacteria which result from secreted metabolic substances – the purine bases – which are a common feature in the label-free SERS research related to clinical diagnostics of pathogens. Here is the review of the current status of SERS applications on bacteria. A special attention is given to the efforts of profiling antimicrobial susceptibility at clinically relevant species, which in turn has a great potential for use in routine point-of-care (POC) tests. Thus, early and accurate infection disease management can be provided at the bedside or at remote care centres.

Sensors ◽  
2021 ◽  
Vol 21 (12) ◽  
pp. 3985
Author(s):  
Nan Wan ◽  
Yu Jiang ◽  
Jiamei Huang ◽  
Rania Oueslati ◽  
Shigetoshi Eda ◽  
...  

A sensitive and efficient method for microRNAs (miRNAs) detection is strongly desired by clinicians and, in recent years, the search for such a method has drawn much attention. There has been significant interest in using miRNA as biomarkers for multiple diseases and conditions in clinical diagnostics. Presently, most miRNA detection methods suffer from drawbacks, e.g., low sensitivity, long assay time, expensive equipment, trained personnel, or unsuitability for point-of-care. New methodologies are needed to overcome these limitations to allow rapid, sensitive, low-cost, easy-to-use, and portable methods for miRNA detection at the point of care. In this work, to overcome these shortcomings, we integrated capacitive sensing and alternating current electrokinetic effects to detect specific miRNA-16b molecules, as a model, with the limit of detection reaching 1.0 femto molar (fM) levels. The specificity of the sensor was verified by testing miRNA-25, which has the same length as miRNA-16b. The sensor we developed demonstrated significant improvements in sensitivity, response time and cost over other miRNA detection methods, and has application potential at point-of-care.


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.


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.


Nanophotonics ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Gianluigi Zito ◽  
Gennaro Sanità ◽  
Bryan Guilcapi Alulema ◽  
Sofía N. Lara Yépez ◽  
Vittorino Lanzio ◽  
...  

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.


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.


The Analyst ◽  
2021 ◽  
Author(s):  
Michael J. Hertaeg ◽  
Rico F. Tabor ◽  
Heather McLiesh ◽  
Gil Garnier

Paper-based diagnostics are leading the field of low-cost, point of care analytical techniques.


Nanophotonics ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 307-316 ◽  
Author(s):  
Jianyang Zhou ◽  
Feng Tao ◽  
Jinfeng Zhu ◽  
Shaowei Lin ◽  
Zhengying Wang ◽  
...  

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.


2015 ◽  
Vol 13 (1) ◽  
Author(s):  
Dominika Pihíková ◽  
Peter Kasák ◽  
Jan Tkac

AbstractGlycosylation of biomolecules is one of the most prevalent post- and co-translational modification in a human body, with more than half of all human proteins being glycosylated. Malignant transformation of cells influences glycosylation machinery resulting in subtle changes of the glycosylation pattern within the cell populations as a result of cancer. Thus, an altered terminal glycan motif on glycoproteins could provide a warning signal about disease development and progression and could be applied as a reliable biomarker in cancer diagnostics. Among all highly effective glycoprofiling tools, label-free electrochemical impedance spectroscopy (EIS)-based biosensors have emerged as especially suitable tool for point-of-care early-stage cancer detection. Herein, we highlight the current challenges in glycoprofiling of various cancer biomarkers by ultrasensitive impedimetric-based biosensors with low sample consumption, low cost fabrication and simple miniaturization. Additionally, this review provides a short introduction to the field of glycomics and lectinomics and gives a brief overview of glycan alterations in different types of cancer.


2017 ◽  
Vol 114 (8) ◽  
pp. E1306-E1315 ◽  
Author(s):  
Rahim Esfandyarpour ◽  
Matthew J. DiDonato ◽  
Yuxin Yang ◽  
Naside Gozde Durmus ◽  
James S. Harris ◽  
...  

Isolation and characterization of rare cells and molecules from a heterogeneous population is of critical importance in diagnosis of common lethal diseases such as malaria, tuberculosis, HIV, and cancer. For the developing world, point-of-care (POC) diagnostics design must account for limited funds, modest public health infrastructure, and low power availability. To address these challenges, here we integrate microfluidics, electronics, and inkjet printing to build an ultra–low-cost, rapid, and miniaturized lab-on-a-chip (LOC) platform. This platform can perform label-free and rapid single-cell capture, efficient cellular manipulation, rare-cell isolation, selective analytical separation of biological species, sorting, concentration, positioning, enumeration, and characterization. The miniaturized format allows for small sample and reagent volumes. By keeping the electronics separate from microfluidic chips, the former can be reused and device lifetime is extended. Perhaps most notably, the device manufacturing is significantly less expensive, time-consuming, and complex than traditional LOC platforms, requiring only an inkjet printer rather than skilled personnel and clean-room facilities. Production only takes 20 min (vs. up to weeks) and $0.01—an unprecedented cost in clinical diagnostics. The platform works based on intrinsic physical characteristics of biomolecules (e.g., size and polarizability). We demonstrate biomedical applications and verify cell viability in our platform, whose multiplexing and integration of numerous steps and external analyses enhance its application in the clinic, including by nonspecialists. Through its massive cost reduction and usability we anticipate that our platform will enable greater access to diagnostic facilities in developed countries as well as POC diagnostics in resource-poor and developing countries.


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