Survey of the year 2004 commercial optical biosensor literature

The year 2004 represents a milestone for the biosensor research community: in this year, over 1000 articles were published describing experiments performed using commercially available systems. The 1038 papers we found represent an approximately 10% increase over the past year and demonstrate that the implementation of biosensors continues to expand at a healthy pace. We evaluated the data presented in each paper and compiled a 'top 10' list. These 10 articles, which we recommend every biosensor user reads, describe well-performed kinetic, equilibrium and qualitative/screening studies, provide comparisons between binding parameters obtained from different biosensor users, as well as from biosensor- and solution-based interaction analyses, and summarize the cutting-edge applications of the technology. We also re-iterate some of the experimental pitfalls that lead to sub-optimal data and over-interpreted results. We are hopeful that the biosensor community, by applying the hints we outline, will obtain data on a par with that presented in the 10 spotlighted articles. This will ensure that the scientific community at large can be confident in the data we report from optical biosensors.     

Survey of the year 2000 commercial optical biosensor literature.

We have compiled a comprehensive list of the articles published in the year 2000 that describe work employing commercial optical biosensors. Selected reviews of interest for the general biosensor user are highlighted. Emerging applications in areas of drug discovery, clinical support, food and environment monitoring, and cell membrane biology are emphasized. In addition, the experimental design and data processing steps necessary to achieve high-quality biosensor data are described and examples of well-performed kinetic analysis are provided.     

Insight of smart biosensors for COVID-19: A review

The review discusses the diagnostic application of biosensors as point-of-care devices in the COVID-19 pandemic. Biosensors are important analytical tools that can be used for the robust and effective detection of infectious diseases in real-time. In this current scenario, the utilization of smart, efficient biosensors for COVID-19 detection is increasing and we have included a few smart biosensors such as smart and intelligent based biosensors, plasmonic biosensors, field effect transistor (FET) biosensors, smart optical biosensors, surface enhanced Raman scattering (SERS) biosensor, screen printed electrode (SPE)-based biosensor, molecular imprinted polymer (MIP)-based biosensor, MXene-based biosensor and metal–organic frame smart sensor. Their significance as well as the benefits and drawbacks of each kind of smart sensor are mentioned in depth. Furthermore, we have compiled a list of various biosensors which have been developed across the globe for COVID-19 and have shown promise as commercial detection devices. Significant challenges in the development of effective diagnostic methods are discussed and recommendations have been made for better diagnostic outcomes to manage the ongoing pandemic effectively.     

Imaging protein activity in live embryos using fluorescence resonance energy transfer biosensors

Fluorescence resonance energy transfer (FRET)-based molecular biosensors serve as important tools for studying protein activity in live cells and have been widely used for this purpose over the past decade. However, FRET biosensors are rarely used in the context of the live organism because of the inherent high cellular complexity and imaging challenges associated with the three-dimensional environment. Here we provide a protocol for using single-chain intramolecular FRET-based biosensors in early development. We provide a general protocol for FRET ratio imaging in embryos, including the data-acquisition conditions and the algorithm for ratio image generation. We then use the pRaichu RacFRET biosensor to exemplify the adaptation and optimization of a particular biosensor for use in live zebrafish embryos. Once an optimized biosensor is available, the complete procedure, including introduction of the probes into embryos, imaging and data analysis, requires 2-3 d.     

Advances in surface plasmon resonance biosensor analysis

The number and diversity of surface plasmon resonance (SPR) biosensor applications continue to increase. Evolutions in instrument and sensor chip technology, experimental methodology, and data analysis are making it possible to examine a wider variety of biomolecular interactions in greater mechanistic detail. SPR biosensors are poised to make a significant impact in basic research and pharmaceutical discovery.     

Determination of affinities and antigenic epitopes of bovine cardiac troponin I (cTnI) with monoclonal antibodies by surface plasmon resonance biosensor

A surface plasmon resonance (SPR) biosensor based on wavelength modulation was used for real-time detection of the interaction of three monoclonal antibodies and antigens of bovine cardiac troponin I (cTnI). In order to recognize antigenic epitopes of bovine cTnI, two experimental modes were applied. In the first experimental mode, three monoclonal antibodies were divided into three groups and three experiments were performed on biosensor surfaces prepared with protein A. In the second experimental mode, antigen was immobilized on the biosensor surface prepared by the amine-coupling method and three monoclonal antibodies were detected in turn. The results obtained by the two modes are consistent. In addition, the affinities of the monoclonal antibodies for the antigen were also determined by the association rate and the disassociation rate in real-time. These results validate the biosensor technology and illustrate how biosensors based on wavelength modulation can be used to study the interaction of monoclonal antibodies and antigens in real time.     

常见生物传感芯片及其应用进展

生物传感芯片是一类综合了生物芯片和生物传感器的优点的新型生物芯片,在保持传统生物芯片的高通量、可寻址、并行处理等特点的基础上,与生物传感器技术相结合,进一步提高了芯片检测的灵敏度和特异性。常见的生物传感芯片主要有光纤传感芯片、表面等离子体共振传感芯片、热生物传感芯片、压电晶体传感芯片等,可用于各种生物大分子,如蛋白质、核酸等的检测,金属离子的测定,病原体的检测,药物筛选等。     

Comparative study of semi-specific Aeromonas hydrophila and universal Pseudomonas fluorescens biosensors for BOD measurements in meat industry wastewaters

Aeromonas hydrophila P69.1 (A. hydrophila) was used to construct a semi-specific biosensor to estimate biochemical oxygen demand (BOD) in high fat and grease content wastewaters. A. hydrophila cells were grown in fat containing medium to induce necessary enzymes for transport and degradation of fatty substances. Universal biosensor based on non-specific Pseudomonas fluorescens P75 (P. fluorescens) was used to conduct comparison experiments. Biosensors were calibrated using OECD synthetic wastewater and steady-state method, subsequently several experiments with synthetic and industrial wastewaters were conducted. A linear range up to 45 mg l(-1) BOD(7) was gained using A. hydrophila biosensor, in comparison to 40 mg l(-1) BOD(7) obtained using P. fluorescens biosensors. The lower limit of detection was 5 mg l(-1) BOD(7). Service life of A. hydrophila and P. fluorescens biosensors were 110 and 115 days, respectively. The response time of the biosensors depended on the BOD(7) of measuring solution and was up to 20 min when analyzing different wastewaters. Both biosensors underestimated BOD in meat industry wastewater from 43% up to 71%, but more accurate results could be obtained with A. hydrophila biosensor. Semi-specific A. hydrophila biosensor was able to measure proportion of fat found in wastewater sample, while other refractory compounds remained undetectable to both biosensors.     

Development and optimisation of biosensors based on pH-sensitive field effect transistors and cholinesterases for sensitive detection of solanaceous glycoalkaloids

Highly sensitive biosensors based on pH-sensitive field effect transistors and cholinesterases for detection of solanaceous glycoalkaloids have been developed, characterised and optimised. The main analytical characteristics of the biosensors developed have been studied under different conditions and an optimal experimental protocol for glycoalkaloids determination in model solution has been proposed. Using such a biosensor and an enzyme reversible inhibition effect, the total potato glycoalkaloids content can be determined within the range of 0.2-100 microM depending on the type of alkaloid, with lowest detection limits of 0.2 microM for alpha-chaconine, 0.5 microM for alpha-solanine and 1 microM for solanidine. The dynamic ranges for the compounds examined show that such biosensors are suitable for a quantitative detection of glycoalkaloids in real potato samples. High reproducibility, operational and storage stability of the biosensor developed have been shown.     

Genetic Programming as a tool for identification of analyte-specificity from complex response patterns using a non-specific whole-cell biosensor

Whole-cell biosensors are mostly non-specific with respect to their detection capabilities for toxicants, and therefore offering an interesting perspective in environmental monitoring. However, to fully employ this feature, a robust classification method needs to be implemented into these sensor systems to allow further identification of detected substances. Substance-specific information can be extracted from signals derived from biosensors harbouring one or multiple biological components. Here, a major task is the identification of substance-specific information among considerable amounts of biosensor data. For this purpose, several approaches make use of statistical methods or machine learning algorithms. Genetic Programming (GP), a heuristic machine learning technique offers several advantages compared to other machine learning approaches and consequently may be a promising tool for biosensor data classification. In the present study, we have evaluated the use of GP for the classification of herbicides and herbicide classes (chemical classes) by analysis of substance-specific patterns derived from a whole-cell multi-species biosensor. We re-analysed data from a previously described array-based biosensor system employing diverse microalgae (Podola and Melkonian, 2005), aiming on the identification of five individual herbicides as well as two herbicide classes. GP analyses were performed using the commercially available GP software 'Discipulus', resulting in classifiers (computer programs) for the binary classification of each individual herbicide or herbicide class. GP-generated classifiers both for individual herbicides and herbicide classes were able to perform a statistically significant identification of herbicides or herbicide classes, respectively. The majority of classifiers were able to perform correct classifications (sensitivity) of about 80-95% of test data sets, whereas the false positive rate (specificity) was lower than 20% for most classifiers. Results suggest that a higher number of data sets may lead to a better classification performance. In the present paper, GP-based classification was combined with a biosensor for the first time. Our results demonstrate GP was able to identify substance-specific information within complex biosensor response patterns and furthermore use this information for successful toxicant classification in unknown samples. This suggests further research to assess perspectives and limitations of this approach in the field of biosensors.     

Heavy metal determination by biosensors based on enzyme immobilised by electropolymerisation

The work describes the original application of biosensors based on enzyme immobilised by electropolymerisation to heavy metal determination. An inhibition detection scheme has been employed for detecting Hg2+ by an established glucose biosensor based on glucose oxidase immobilised in poly-o-phenylenediamine. The investigated enzymatic inhibition appears reversible and mixed, in agreement with data for the enzyme in solution. A low response time (<2 min) and a rapid recovery of response by EDTA seem the most interesting characteristics of the proposed biosensor at the present stage of development, along with the well known easy preparation of this kind of biosensors. The occurrence of a high response also for Cu2+ opens the possibility to apply the biosensor in total toxic metal content determination.     

Biosensor Architectures for High-Fidelity Reporting of Cellular Signaling

Understanding mechanisms of information processing in cellular signaling networks requires quantitative measurements of protein activities in living cells. Biosensors are molecular probes that have been developed to directly track the activity of specific signaling proteins and their use is revolutionizing our understanding of signal transduction. The use of biosensors relies on the assumption that their activity is linearly proportional to the activity of the signaling protein they have been engineered to track. We use mechanistic mathematical models of common biosensor architectures (single-chain FRET-based biosensors), which include both intramolecular and intermolecular reactions, to study the validity of the linearity assumption. As a result of the classic mechanism of zero-order ultrasensitivity, we find that biosensor activity can be highly nonlinear so that small changes in signaling protein activity can give rise to large changes in biosensor activity and vice versa. This nonlinearity is abolished in architectures that favor the formation of biosensor oligomers, but oligomeric biosensors produce complicated FRET states. Based on this finding, we show that high-fidelity reporting is possible when a single-chain intermolecular biosensor is used that cannot undergo intramolecular reactions and is restricted to forming dimers. We provide phase diagrams that compare various trade-offs, including observer effects, which further highlight the utility of biosensor architectures that favor intermolecular over intramolecular binding. We discuss challenges in calibrating and constructing biosensors and highlight the utility of mathematical models in designing novel probes for cellular signaling.     

On-line microbial biosensing and fingerprinting of water pollutants

The potential for biosensors to contribute to on-line toxicity testing for monitoring of water quality is currently constrained both by the relevance of the biosensors available and the technology for biosensor delivery. This paper reports the use of novel slow release biosensor delivery for on-line monitoring instrumentation, with environmentally relevant bacteria for both simple toxicity testing and more complex toxicity fingerprinting of industrial effluents. The on-line toxicity test, using bioluminescence-based biosensors, proved to be as sensitive and reliable as the corresponding batch test, with comparable contaminant EC(50) values from both methods. Toxicity fingerprinting through the investigation of the kinetics (dose-response) and the dynamics (response with time) of the biosensor test response proved to be diagnostic of both effluent type and composition. Furthermore, the slow release of biosensors immobilised in a polyvinyl alcohol (PVA) matrix greatly improved biosensor delivery, did not affect the sensitivity of toxicity testing, and demonstrated great potential for inclusion in on-line monitoring instrumentation.     

A versatile biosensor device for continuous biomedical monitoring

Although biosensors are by means suitable for continuous biomedical monitoring, due to fouling and blood clotting, in vivo performance is far from optimal. For this reason, ultrafiltration, microdialysis or open tubular flow is frequently used as interface. To secure quantitative recoveries of the analyte of interest, sampling at submicrolitre level will be necessary which in turn necessitates the development of small and versatile biosensor devices. Here, a miniaturised biosensor device, which directly can be connected to various interfaces will be presented. The biosensor device consists of a pulsefree pump and a biosensor with an internal volume of 10–20 nl. In this article, the production as well as the construction of the flow-through cell of the biosensor will be discussed. The advantages and disadvantages of several production processes will be demonstrated and a detailed protocol for the production of such a nanoliter flow-through cell will be presented. With respect to the bio-selector, several permselective membranes have been tested on their performance characteristics. Results obtained with these biosensors will be presented and discussed. Finally, a protocol based upon in situ electropolymerisation for the immobilisation of the biological component was defined and several biosensors based upon this principle have been produced and tested for the monitoring of glucose respectively lactate. To demonstrate, data obtained during a variety of in vivo studies at different clinical relevant applications will be presented.     

Biosensor Architectures for High-Fidelity Reporting of Cellular Signaling

Understanding mechanisms of information processing in cellular signaling networks requires quantitative measurements of protein activities in living cells. Biosensors are molecular probes that have been developed to directly track the activity of specific signaling proteins and their use is revolutionizing our understanding of signal transduction. The use of biosensors relies on the assumption that their activity is linearly proportional to the activity of the signaling protein they have been engineered to track. We use mechanistic mathematical models of common biosensor architectures (single-chain FRET-based biosensors), which include both intramolecular and intermolecular reactions, to study the validity of the linearity assumption. As a result of the classic mechanism of zero-order ultrasensitivity, we find that biosensor activity can be highly nonlinear so that small changes in signaling protein activity can give rise to large changes in biosensor activity and vice versa. This nonlinearity is abolished in architectures that favor the formation of biosensor oligomers, but oligomeric biosensors produce complicated FRET states. Based on this finding, we show that high-fidelity reporting is possible when a single-chain intermolecular biosensor is used that cannot undergo intramolecular reactions and is restricted to forming dimers. We provide phase diagrams that compare various trade-offs, including observer effects, which further highlight the utility of biosensor architectures that favor intermolecular over intramolecular binding. We discuss challenges in calibrating and constructing biosensors and highlight the utility of mathematical models in designing novel probes for cellular signaling.     

Survey of the 1999 surface plasmon resonance biosensor literature

The application of surface plasmon resonance biosensors in life sciences and pharmaceutical research continues to increase. This review provides a comprehensive list of the commercial 1999 SPR biosensor literature and highlights emerging applications that are of general interest to users of the technology. Given the variability in the quality of published biosensor data, we present some general guidelines to help increase confidence in the results reported from biosensor analyses.     

Large Scale Bacterial Colony Screening of Diversified FRET Biosensors

Biosensors based on Förster Resonance Energy Transfer (FRET) between fluorescent protein mutants have started to revolutionize physiology and biochemistry. However, many types of FRET biosensors show relatively small FRET changes, making measurements with these probes challenging when used under sub-optimal experimental conditions. Thus, a major effort in the field currently lies in designing new optimization strategies for these types of sensors. Here we describe procedures for optimizing FRET changes by large scale screening of mutant biosensor libraries in bacterial colonies. We describe optimization of biosensor expression, permeabilization of bacteria, software tools for analysis, and screening conditions. The procedures reported here may help in improving FRET changes in multiple suitable classes of biosensors.