Development of Optical Biosensor Technologies for Cardiac Troponin Recognition

Acute myocardial infarction (AMI) is the leading cause of death among cardiovascular diseases. Among the numerous attempts to develop coronary marker concepts into clinical strategies, cardiac troponin is known as a specific marker for coronary events. The cardiac troponin concentration level in blood has been shown to rise rapidly for 4–10 days after onset of AMI, making it an attractive approach for a long diagnosis window for detection. The extremely low clinical sensing range of cardiac troponin levels consequently makes the methods of detection highly sensitive. In this review, by taking into consideration optical methods applied for cardiac troponin detection, we discuss the most commonly used methods of optical immunosensing and provide an overview of the various diagnostic cardiac troponin immunosensors that have been employed for determination of cardiac troponin over the last several years

Recent Progress in Optical Sensors for Biomedical Diagnostics

In recent years, several types of optical sensors have been probed for their aptitude in healthcare biosensing, making their applications in biomedical diagnostics a rapidly evolving subject. Optical sensors show versatility amongst different receptor types and even permit the integration of different detection mechanisms. Such conjugated sensing platforms facilitate the exploitation of their neoteric synergistic characteristics for sensor fabrication. This paper covers nearly 250 research articles since 2016 representing the emerging interest in rapid, reproducible and ultrasensitive assays in clinical analysis. Therefore, we present an elaborate review of biomedical diagnostics with the help of optical sensors working on varied principles such as surface plasmon resonance, localised surface plasmon resonance, evanescent wave fluorescence, bioluminescence and several others. These sensors are capable of investigating toxins, proteins, pathogens, disease biomarkers and whole cells in varied sensing media ranging from water to buffer to more complex environments such as serum, blood or urine. Hence, the recent trends discussed in this review hold enormous potential for the widespread use of optical sensors in early-stage disease prediction and point-of-care testing devices.DFG, 428780268, Biomimetische Rezeptoren auf NanoMIP-Basis zur Virenerkennung und -entfernung mittels integrierter Ansätz

MicroRNA detection on microsensor arrays by SPR imaging measurements with enzymatic signal enhancement.

We investigated sequence-specific and simultaneous microRNA (miRNA) detections by surface plasmon resonance (SPR) imaging measurements on SPR chips possessing an Au spot array modified with probe DNAs based on a miRNA-detection-selective SPR signal amplification method. MiRNAs were detected with the detection limit of the attomole level by SPR imaging measurements for different miRNA concentrations on a single chip. SPR signals were enhanced based on a combination process of sequence-specific hybridization of the miRNA to the probe DNAs, extension reaction of polyadenine (poly(A)) tails by poly(A) polymerase, binding of a ternary complex of T30-biotin/horseradish peroxidase (HRP)-biotin/streptavidin to the poly(A) tails, and the oxidation reaction of tetramethylbenzidine (TMB) on the HRP by providing a blue precipitate on the surface. This process sequence-specifically and dramatically amplified the SPR signals. This is a simple, cost-effective, and feasible signal amplification method based on the organic compound TMB instead of metal nanoparticles

Ultrasensitive detection of lipoarabinomannan with plasmonic grating biosensors in clinical samples of HIV negative patients with tuberculosis.

BACKGROUND:Timely diagnosis of tuberculosis disease is critical for positive patient outcomes, yet potentially millions go undiagnosed or unreported each year. Sputum is widely used as the testing input, but limited by its complexity, heterogeneity, and sourcing problems. Finding methods to interrogate noninvasive, non-sputum clinical specimens is indispensable to improving access to tuberculosis diagnosis and care. In this work, economical plasmonic gratings were used to analyze tuberculosis biomarker lipoarabinomannan (LAM) from clinical urine samples by single molecule fluorescence assay (FLISA) and compared with gold standard sputum GeneXpert MTB/ RIF, culture, and reference ELISA testing results. METHODS AND FINDINGS:In this study, twenty sputum and urine sample sets were selected retrospectively from a repository of HIV-negative patient samples collected before initiation of anti-tuberculosis therapy. GeneXpert MTB/RIF and culture testing of patient sputum confirmed the presence or absence of pulmonary tuberculosis while all patient urines were reference ELISA LAM-negative. Plasmonic gratings produced by low-cost soft lithography were bound with anti-LAM capture antibody, incubated with patient urine samples, and biotinylated detection antibody. Fluorescently labeled streptavidin revealed single molecule emission by epifluorescence microscope. Using a 1 fg/mL baseline for limit of detection, single molecule FLISA demonstrated good qualitative agreement with gold standard tests on 19 of 20 patients, including accurately predicting the gold-standard-negative patients, while one gold-standard-positive patient produced no observable LAM in urine. CONCLUSIONS:Single molecule FLISA by plasmonic grating demonstrated the ability to quantify tuberculosis LAM from complex urine samples of patients from a high endemic setting with negligible interference from the complex media itself. Moreover, agreement with patient diagnoses by gold standard testing suggests that single molecule FLISA could be used as a highly sensitive test to diagnose tuberculosis noninvasively

Present and future of surface-enhanced Raman scattering

The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article

Field Effect Transistor Nanosensor for Breast Cancer Diagnostics

Silicon nanochannel field effect transistor (FET) biosensors are one of the most promising technologies in the development of highly sensitive and label-free analyte detection for cancer diagnostics. With their exceptional electrical properties and small dimensions, silicon nanochannels are ideally suited for extraordinarily high sensitivity. In fact, the high surface-to-volume ratios of these systems make single molecule detection possible. Further, FET biosensors offer the benefits of high speed, low cost, and high yield manufacturing, without sacrificing the sensitivity typical for traditional optical methods in diagnostics. Top down manufacturing methods leverage advantages in Complementary Metal Oxide Semiconductor (CMOS) technologies, making richly multiplexed sensor arrays a reality. Here, we discuss the fabrication and use of silicon nanochannel FET devices as biosensors for breast cancer diagnosis and monitoring

Biosensors for cardiac biomarkers detection: a review

The cardiovascular disease (CVD) is considered as a major threat to global health. Therefore, there is a growing demand for a range of portable, rapid and low cost biosensing devices for the detection of CVD. Biosensors can play an important role in the early diagnosis of CVD without having to rely on hospital visits where expensive and time-consuming laboratory tests are recommended. Over the last decade, many biosensors have been developed to detect a wide range of cardiac marker to reduce the costs for healthcare. One of the major challenges is to find a way of predicting the risk that an individual can suffer from CVD. There has been considerable interest in finding diagnostic and prognostic biomarkers that can be detected in blood and predict CVD risk. Of these, C-reactive protein (CRP) is the best known biomarker followed by cardiac troponin I or T (cTnI/T), myoglobin, lipoprotein-associated phospholipase A(2), interlukin-6 (IL-6), interlukin-1 (IL-1), low-density lipoprotein (LDL), myeloperoxidase (MPO) and tumor necrosis factor alpha (TNF-α) has been used to predict cardiovascular events. This review provides an overview of the available biosensor platforms for the detection of various CVD markers and considerations of future prospects for the technology are addressed

Smart and Functional Interfaces for Sensitive SPR Biosensing Towards Biomedical Applications

The aim of this thesis is to develop Surface Plasmon Resonance (SPR) methods that improve biosensing performance, in particular the sensitivity and selectivity of the analysis and their adaptation for biomedical applications to samples with complex background. This is of significant importance in translating the biosensor technologies to deliver the same results as the conventional methods but in a more accessible, efficient, and economical manner. The first study exploited SPR as a DNA biosensor for the detection of Malaria Plasmodium falciparum parasite with the hybridization chain reaction (HCR), which resulted in the formation of self-assembled target DNA nanostructures for signal enhancement. The sensitivity was further improved by using gold nanoparticles (AuNPs) for additional signal amplification. Tests with human blood plasma indicated the results were comparable to analyses in buffer, despite noticeable non-specific binding from the plasma. The concern of non-specific binding was systematically investigated in the second study where an antifouling surface consists of supported lipid bilayer membranes (SLBs) and protein A was developed for detection of trace amount of proteins in undiluted human serum. Specifically, cholera toxin (CT) spiked into the serum was used as the target, and advanced interface was further extended to immunosensing of immunoglobulin G (IgG). In the third study, SPR biosensor was employed in combination of bright field microscopy to characterize cellular apoptosis. HeLa cells undergoing apoptosis induced by hydrogen peroxide (H2O2) were monitored by SPR and the signals were compared to microscopic analysis of the morphological changes. SPR study revealed a decreased signal as cell confluency decreases, with the rates increasing as H2O2 concentration increases. An abnormality was found at high concentrations when both apoptosis and necrosis were induced. A mathematical model was proposed to explain SPR response where a non- uniform adsorbed layer was partially responsible. The significance of this thesis is that a number of high performing biosensing approaches have been developed and demonstrated. In addition to the advantages of SPR (e.g. label-free, real-time biomolecules binding, and portability), these methods have paved the way towards realizing effective sensing in biomedical research, especially in the early detection of infectious diseases and in the treatment of cancers