Optical fiber-based sensors: application to chemical biology

Optical fibers have been used to develop sensors based on nucleic acids and cells. Sensors employing DNA probes have been developed for various genomics applications and microbial pathogen detection. Live cell-based sensors have enabled the monitoring of environmental toxins, and have been used for fundamental studies on populations of individual cells. Both single-core optical fiber sensors and optical fiber sensor arrays have been used for sensing based on nucleic acids and live cells.     

The design and development of new chemical sensors for in vivo monitoring.

The latest workshop of the European Community (EC) Concerted Action on 'Chemical sensors for in vivo monitoring' was held in Nauplion, Greece, in April this year. This fifth workshop focused on 'The design and development of new sensors for in vivo monitoring', and was organized into five sessions: design and development of new sensors; operational considerations; performance of analytical systems; novel sensors/tissue heterogeneity; and infra-red spectroscopy.     

Neurons as sensors: individual and cascaded chemical sensing

A single neuron sensor has been developed based on the interaction of gradient electric fields and the cell membrane. Single neurons are rapidly positioned over individual microelectrodes using positive dielectrophoretic traps. This enables the continuous extracellular electrophysiological measurements from individual neurons. The sensor developed using this technique provides the first experimental method for determining single cell sensitivity; the speed of response and the associated physiological changes to a broad spectrum of chemical agents. Binding of specific chemical agents to a specific combination of receptors induces changes to the extracellular membrane potential of a single neuron, which can be translated into unique “signature patterns” (SP), which function as identification tags. Signature patterns are derived using Fast Fourier Transformation (FFT) analysis and Wavelet Transformation (WT) analysis of the modified extracellular action potential. The validity and the sensitivity of the system are demonstrated for a variety of chemical agents ranging from behavior altering chemicals (ethanol), environmentally hazardous agents (hydrogen peroxide, EDTA) to physiologically harmful agents (pyrethroids) at pico- and femto-molar concentrations. The ability of a single neuron to selectively identify specific chemical agents when injected in a serial manner is demonstrated in “cascaded sensing”.     

Collection mode surface plasmon fibre sensors: a new biosensing platform

Sensors based on surface plasmon resonance (SPR) allow rapid, label-free, highly sensitive detection, and indeed this phenomenon underpins the only label-free optical biosensing technology that is available commercially. In these sensors, the existence of surface plasmons is inferred indirectly from absorption features that correspond to the coupling of light into a thin metallic film. Although SPR is not intrinsically a radiative process, when the metallic coating which support the plasmonic wave exhibits a significant surface roughness, the surface plasmon can itself couple to the local photon states, and emit light. Here we show that using silver coated optical fibres, this novel SPR transducing mechanism offers significant advantages compare to traditional reflectance based measurements such as lower dependency on the metallic thickness and higher signal to noise ratio. Furthermore, we show that more complex sensor architectures with multiple sensing regions scattered along a single optical fibre enable multiplexed detection and dynamic self referencing of the sensing signal. Moreover, this alternative approach allows to combine two different sensing technologies, SPR and fluorescence sensing within the same device, which has never been demonstrated previously. As a preliminary proof of concept of potential application, this approach has been used to demonstrate the detection of the seasonal influenza A virus.     

Review of chemical sensors for physiological measurement

The continuous measurement of chemical species is important for physiological and biochemical research and for critical care medicine. Chemical sensors are being developed for the measurement of a wide range of analytes, especially gases, vapours, ions, catabolites, drugs and hormones. The mechanical form of these sensors may be adapted for use in single cells, tissue fluid and blood vessels, on the skin surface, in the respiratory and gastrointestinal systems. Optical and electro-chemical principles are now used widely for sensor design, and advances in electronic fabrication methods and in optical fibres, sources, and detectors, have been important.     

Clinicians'' requirements for chemical sensors for in vivo monitoring: a multinational survey.

We report on a survey of senior clinicians in 11 countries which asked about what they see as the main areas where in vivo chemical sensors will be most useful in medicine, and about what their operating characteristics should be. This information may help those designing such sensors to match available and new technologies to clinical needs.     

Implantable chemical sensors for real-time clinical monitoring: progress and challenges

Recently, progress has been made in the development of implantable chemical sensors capable of real-time monitoring of clinically important species such as PO(2), PCO(2), pH, glucose and lactate. The need for developing truly biocompatible materials for sensor fabrication remains the most significant challenge for achieving robust and reliable sensors capable of monitoring the real-time physiological status of patients.     

Intramembrane-sensing histidine kinases: a new family of cell envelope stress sensors in Firmicutes bacteria

Two-component signal-transducing systems (TCS) consist of a histidine kinase (HK) that senses a specific environmental stimulus, and a cognate response regulator (RR) that mediates the cellular response. Most HK are membrane-anchored proteins harboring two domains: An extracytoplasmic input and a cytoplasmic transmitter (or kinase) domain, separated by transmembrane helices that are crucial for the intramolecular information flow. In contrast to the cytoplasmic domain, the input domain is highly variable, reflecting the plethora of different signals sensed. Intramembrane-sensing HK (IM-HK) are characterized by their short input domain, consisting solely of two putative transmembane helices. They lack an extracytoplasmic domain, indicative for a sensing process at or from within the membrane interface. Most proteins sharing this domain architecture are found in Firmicutes bacteria. Two major groups can be differentiated based on sequence similarity and genomic context: (1) BceS-like IM-HK that are functionally and genetically linked to ABC transporters, and (2) LiaS-like IM-HK, as part of three-component systems. Most IM-HK sense cell envelope stress, and identified target genes are often involved in maintaining cell envelope integrity, mediating antibiotic resistance, or detoxification processes. Therefore, IM-HK seem to constitute an important mechanism of cell envelope stress response in low G+C Gram-positive bacteria.     

Sniffing out cancer using “chemical nose” sensors

Comment on: Bajaj A, et al. Proc Nat Acad Sci 2009; 106:10912-16.     

Molecular photonic and electronic circuitry for ultra-sensitive chemical sensors

Molecular wires have progressed from an intellectual curiosity to become the basis for chemical sensors with unprecedented sensitivity. Particularly exciting opportunities are those that make use of biological superstructures to effect conduction through assemblies of molecular wires.     

Utilization of biosensors and chemical sensors for space applications.

There will be a need for a wide array of chemical sensors for biomedical experimentation and for the monitoring of water and air recycling processes on Space Station Freedom. The infrequent logistics flights of the Space Shuttle will necessitate onboard analysis. The advantages of biosensors and chemical sensors over conventional analysis onboard spacecraft are manifold. They require less crew time, space, and power. Sample treatment is not needed. Real time or near-real time monitoring is possible, in some cases on a continuous basis. Sensor signals in digitized form can be transmitted to the ground. Types and requirements for chemical sensors to be used in biomedical experimentation and monitoring of water recycling during long-term space missions are discussed.     

Functional asymmetry and chemical reactivity of CsoR family persulfide sensors

CstR is a persulfide-sensing member of the functionally diverse copper-sensitive operon repressor (CsoR) superfamily. While CstR regulates the bacterial response to hydrogen sulfide (H₂S) and more oxidized reactive sulfur species (RSS) in Gram-positive pathogens, other dithiol-containing CsoR proteins respond to host derived Cu(I) toxicity, sometimes in the same bacterial cytoplasm, but without regulatory crosstalk in cells. It is not clear what prevents this crosstalk, nor the extent to which RSS sensors exhibit specificity over other oxidants. Here, we report a sequence similarity network (SSN) analysis of the entire CsoR superfamily, which together with the first crystallographic structure of a CstR and comprehensive mass spectrometry-based kinetic profiling experiments, reveal new insights into the molecular basis of RSS specificity in CstRs. We find that the more N-terminal cysteine is the attacking Cys in CstR and is far more nucleophilic than in a CsoR. Moreover, our CstR crystal structure is markedly asymmetric and chemical reactivity experiments reveal the functional impact of this asymmetry. Substitution of the Asn wedge between the resolving and the attacking thiol with Ala significantly decreases asymmetry in the crystal structure and markedly impacts the distribution of species, despite adopting the same global structure as the parent repressor. Companion NMR, SAXS and molecular dynamics simulations reveal that the structural and functional asymmetry can be traced to fast internal dynamics of the tetramer. Furthermore, this asymmetry is preserved in all CstRs and with all oxidants tested, giving rise to markedly distinct distributions of crosslinked products. Our exploration of the sequence, structural, and kinetic features that determine oxidant-specificity suggest that the product distribution upon RSS exposure is determined by internal flexibility.     

Cataluminescence‐based sensors: principle,instrument and application

The cataluminescence (CTL)‐based sensor is a new promising type of chemical transducer, and has attracted much attention of researchers for its potential versatile applications in public safety, emission control and environmental protection. In this review, we briefly introduce the development history of CTL‐based sensors and summarize existing explanations of the CTL reaction mechanism as well as three research strategies for mechanism the CTL mechanism. In the following, all the function units of a typical CTL‐based sensor system are described and the investigation of the sensor materials. CTL‐based sensor arrays, are discussed in detail. We classify the recent novel hyphenated techniques based on CTL coupled to other analysis techniques into the preconcentration‐CTL hyphenated technique, nebulization‐CTL hyphenated technique, plasma‐assisted CTL technique and tandem CTL technique according to the type of analysis combined with CTL and provide a detailed account of novel hyphenated techniques. Owing to the appearance of these novel techniques, the application range of CTL has been expanded as well as the sensitivity and selectivity of CTL system has been greatly improved. Finally, the applications of CTL‐based sensor and sensor arrays in the last several years are classified and summarized. Copyright © 2014 John Wiley & Sons, Ltd.     

Surface plasmon resonance sensors in cell biology: basics and application

Optical sensors based on the excitation of surface plasmons, referred to as surface plasmon resonance (SPR) sensors, have become a central analytical tool for characterizing and quantifying a wide variety of macromolecular interactions, like receptor–ligand contacts. Besides this classical field of application, in the last 15 years, the development of SPR sensors aiming for the detection and analysis of ligand/cell or host/pathogen interactions, cell/cell contacts, and cellular reactions gained considerable momentum. The number of publications reporting about applications of SPR sensors implementing vital prokaryotic or eukaryotic cells as biorecognition elements for medical diagnostics, environmental monitoring, or biological safety is steadily growing. This review gives a short introduction to the technique of surface plasmon resonance and the parameters that are important for its application in the field of vital cell sensors. Furthermore, the publications concerning the application of such sensors in the analysis of cellular interactions and cellular reactions to extra- and intracellular stimuli are summarized.     

MCMC multilocus lod scores: application of a new approach

On extended pedigrees with extensive missing data, the calculation of multilocus likelihoods for linkage analysis is often beyond the computational bounds of exact methods. Growing interest therefore surrounds the implementation of Monte Carlo estimation methods. In this paper, we demonstrate the speed and accuracy of a new Markov chain Monte Carlo method for the estimation of linkage likelihoods through an analysis of real data from a study of early-onset Alzheimer's disease. For those data sets where comparison with exact analysis is possible, we achieved up to a 100-fold increase in speed. Our approach is implemented in the program lm_bayes within the framework of the freely available MORGAN 2.6 package for Monte Carlo genetic analysis (http://www.stat.washington.edu/thompson/Genepi/MORGAN/Morgan.shtml).     

Nano-biophotonics: new tools for chemical nano-analytics

The nondestructive chemical analysis of biological processes in the crowded intracellular environment, at cellular membranes, and between cells with a spatial resolution well beyond the diffraction limit is made possible through Nano-Biophotonics. A number of sophisticated schemes employing nanoparticles, nano-apertures, or shaping of the probe volume in the far field have significantly extended our knowledge about lipid rafts, macromolecular complexes, such as chromatin, vesicles, and cellular organelles, and their interactions and trafficking within the cell. Here, I review some of the most recent developments in Nano-Biophotonics that already are or soon will become relevant to the analysis of intracellular processes. The pros and cons of the various techniques will be discussed and an outlook of their prospects for the near future will be provided.     

Seq2Enz: An application of mask BLAST methodology with a new chemical logic of amino acids for improved enzyme function prediction

Seq2Enz method is a new way to identify whether a query protein sequence is an enzyme and to assign an enzyme class to the protein sequence. The method is based on mask BLAST fortified with some novel structural-chemical properties (NCL) of the building blocks of proteins. All available reviewed enyme sequences (267,276 in number) in Uniprot/SwissProt and most recent depositions (7062) not used for training in ECPred, a state of the art software for enzyme class prediction, are taken for assessment and the results are compared with those from conventional BLAST and ECPred respectively. Seq2Enz is seen to perform consistently better for all the enzyme classes to all the four levels. Seq2Enz methodology is converted into an easy to use web-server and made freely accessible at http://www.scfbio-iitd.res.in Seq2Enz/.