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”.     

Multidimensional Mapping Method Using an Arrayed Sensing System for Cross-Reactivity Screening

When measuring chemical information in biological fluids, challenges of cross-reactivity arise, especially in sensing applications where no biological recognition elements exist. An understanding of the cross-reactions involved in these complex matrices is necessary to guide the design of appropriate sensing systems. This work presents a methodology for investigating cross-reactions in complex fluids. First, a systematic screening of matrix components is demonstrated in buffer-based solutions. Second, to account for the effect of the simultaneous presence of these species in complex samples, the responses of buffer-based simulated mixtures of these species were characterized using an arrayed sensing system. We demonstrate that the sensor array, consisting of electrochemical sensors with varying input parameters, generated differential responses that provide synergistic information of sample. By mapping the sensing array response onto multidimensional heat maps, characteristic signatures were compared across sensors in the array and across different matrices. Lastly, the arrayed sensing system was applied to complex biological samples to discern and match characteristic signatures between the simulated mixtures and the complex sample responses. As an example, this methodology was applied to screen interfering species relevant to the application of schizophrenia management. Specifically, blood serum measurement of antipsychotic clozapine and antioxidant species can provide useful information regarding therapeutic efficacy and psychiatric symptoms. This work proposes an investigational tool that can guide multi-analyte sensor design, chemometric modeling and biomarker discovery.     

Carbon nanotube based aliphatic hydrocarbon sensor

A hybrid multi-walled carbon nanotube (MWCNT) based chemical sensor was designed and developed by integration of microfabrication techniques with nano-assembly. This integrated sensing mechanism on a chip, comprised of thiol functionalized MWCNTs that functioned as transducers which were integrated with micro-electrode array measurement sites. The detection of the four fundamental hydrocarbons belonging to the aliphatic hydrocarbon family--methanol, ethanol, propanol and butanol was experimentally demonstrated. High degree of selectivity was demonstrated by repeated robust identification of individual hydro carbons belonging to the same family. The sensor demonstrated 1 ppm detection sensitivity. The detection mechanism was based on nano-scale transduction of the detection of the localized binding event between the functional binding sites and the chemical species of interest. Specific electrical signatures for each of these chemicals were identified using multiple levels of data analysis comprising of Fast Fourier Transformation (FFT) and Power Spectral Density (PSD). The sensor demonstrated a rapid response time with portability, accuracy and versatility for the in situ detection of multiple chemical agents, with potential for automation.     

Structure and function of the voltage sensor of sodium channels probed by a beta-scorpion toxin

Voltage sensing by voltage-gated sodium channels determines the electrical excitability of cells, but the molecular mechanism is unknown. beta-Scorpion toxins bind specifically to neurotoxin receptor site 4 and induce a negative shift in the voltage dependence of activation through a voltage sensor-trapping mechanism. Kinetic analysis showed that beta-scorpion toxin binds to the resting state, and subsequently the bound toxin traps the voltage sensor in the activated state in a voltage-dependent but concentration-independent manner. The rate of voltage sensor trapping can be fit by a two-step model, in which the first step is voltage-dependent and correlates with the outward gating movement of the IIS4 segment, whereas the second step is voltage-independent and results in shifted voltage dependence of activation of the channel. Mutations of Glu(779) in extracellular loop IIS1-S2 and both Glu(837) and Leu(840) in extracellular loop IIS3-S4 reduce the binding affinity of beta-scorpion toxin. Mutations of positively charged and hydrophobic amino acid residues in the IIS4 segment do not affect beta-scorpion toxin binding but alter voltage dependence of activation and enhance beta-scorpion toxin action. Structural modeling with the Rosetta algorithm yielded a three-dimensional model of the toxin-receptor complex with the IIS4 voltage sensor at the extracellular surface. Our results provide mechanistic and structural insight into the voltage sensor-trapping mode of scorpion toxin action, define the position of the voltage sensor in the resting state of the sodium channel, and favor voltage-sensing models in which the S4 segment spans the membrane in both resting and activated states.     

Enzyme-based sensor arrays for rapid characterization of complex disaccharide solutions

An enzyme-based sensor array has been developed to detect multiple disaccharides in aqueous solutions. Porous agarose beads, derivatized with enzymes for assaying disaccharides, are localized within wells etched into a silicon chip in a regular 5 x 7 array. Each well is individually addressable and acts as a microanalysis chamber where sample solution passes through the agarose matrix and is exposed to the enzymes. Detection is achieved by observing the increase in absorbance of a quinoneimine dye produced during the reaction. This technique is used to quantify the disaccharides lactose, sucrose, and maltose and the monosaccharide glucose. Preexisting glucose in the sample complicates multicomponent sensing but can be accounted for by including a glucose sensor in the array. This detection strategy is applied to the simultaneous analysis of these sugars in several beverages.     

The morphology of the rat vibrissal array: a model for quantifying spatiotemporal patterns of whisker-object contact

In all sensory modalities, the data acquired by the nervous system is shaped by the biomechanics, material properties, and the morphology of the peripheral sensory organs. The rat vibrissal (whisker) system is one of the premier models in neuroscience to study the relationship between physical embodiment of the sensor array and the neural circuits underlying perception. To date, however, the three-dimensional morphology of the vibrissal array has not been characterized. Quantifying array morphology is important because it directly constrains the mechanosensory inputs that will be generated during behavior. These inputs in turn shape all subsequent neural processing in the vibrissal-trigeminal system, from the trigeminal ganglion to primary somatosensory ("barrel") cortex. Here we develop a set of equations for the morphology of the vibrissal array that accurately describes the location of every point on every whisker to within ±5% of the whisker length. Given only a whisker's identity (row and column location within the array), the equations establish the whisker's two-dimensional (2D) shape as well as three-dimensional (3D) position and orientation. The equations were developed via parameterization of 2D and 3D scans of six rat vibrissal arrays, and the parameters were specifically chosen to be consistent with those commonly measured in behavioral studies. The final morphological model was used to simulate the contact patterns that would be generated as a rat uses its whiskers to tactually explore objects with varying curvatures. The simulations demonstrate that altering the morphology of the array changes the relationship between the sensory signals acquired and the curvature of the object. The morphology of the vibrissal array thus directly constrains the nature of the neural computations that can be associated with extraction of a particular object feature. These results illustrate the key role that the physical embodiment of the sensor array plays in the sensing process.     

A composite sensor array impedentiometric electronic tongue Part I. Characterization

A study aimed at the characterization of five compounds with different chemical characteristics and gustative perceptions by measuring the variations of the electrical impedance of a composite sensor array is presented. The array was composed of five sensors of three different types based on carbon nanotubes or carbon black dispersed in polymeric matrices and doped polythiophenes. Measurements were carried out by evaluating the electrical impedance of the sensor array at a frequency of 150 Hz, and the data acquisition process was automated; a mechanical arm and a rotating platform controlled by a data acquisition card and a dedicated software allowed the sequential dipping of sensors in the test solutions. Fifty different solutions eliciting the 5 basic tastes (sodium chloride, citric acid, glucose, glutamic acid and sodium dehydrocholate for salty, sour, sweet, umami and bitter, respectively) at 10 concentration levels comprising the human perceptive range were analysed. More than 100 measurements were carried for each sample in a 4-month period to evaluate the system repeatability and robustness. The impedentiometric composite sensor array is shown to be sensitive, selective and stable for use in an electronic tongue.     

Colorimetric artificial tongue for protein identification

Artificial tongue systems are multisensory devices which are highly desirable for the analysis and recognition of complicated composition samples. Herein, a low-cost and simple colorimetric sensor array for identification and quantification of proteins were reported. Using prophyrin, porphyrin derivatives (mainly metalloporphyrins) and chemically responsive dyes as the sensing elements, the developed sensor array of artificial tongue showed a unique pattern of colorific change upon its exposure to proteins. The composite pattern for each sample was subjected to principal component analysis (PCA), thus providing a clustering map for more practical visualization. All the pure and mixed proteins, as well as denatured proteins, gave distinct patterns, thus resulting in their unambiguous identification. The PCA analysis also suggested that the unique pattern of colorific change may be due to the change of protein conformation and local environmental pH. These results demonstrate that the developed colorimetric artificial tongue system is an excellent sensing platform for identification and quantitative analysis of protein samples.     

USE OF CHEMICAL SENSOR ARRAYS FOR FOOD AND FRAGRANCE ANALYSIS

Many workers have recently developed and demonstrated the use of gas sensor arrays to detect and recognize a variety of compounds. In general, a pattern recognition approach is used in which the signature of an unknown sample is compared to a library of signatures of known substances. All of these efforts have shown varying degrees of success when applied to pure compounds. Unfortunately, flavors and fragrances are never pure compounds. A prototype gas sensor array has been constructed and tested with various mixtures of interest. The results are discussed in terms of their implication to the food and fragrance industry. Early experiments on gasoline-alcohol mixtures demonstrated that the signatures do not follow a rule of mixing, but were more strongly influenced by the more volatile and/or more reactive component. This led us to examine the behavior of alcohol-water mixtures for possible quality control in the distilling industry. We discovered that the signature of alcohol dominated even at concentrations as low as ten percent. Preliminary experiments were also performed to see if the prototype sensor array could be used to automatically detect rancidity in dairy products. Flavorings and essential oils are in many cases even more complex mixtures. The behavior of representative classes of these substances were characterized in an attempt to understand their signatures on the basis of their constituents.     

An array of field-effect nanoplate SOI capacitors for (bio-)chemical sensing

An array of individually addressable nanoplate field-effect capacitive (bio-)chemical sensors based on an SOI (silicon-on-insulator) structure has been developed. The isolation of the individual capacitors was achieved by forming a trench in the top Si layer with a thickness of 350 nm. The realized sensor array allows addressable biasing and electrical readout of multiple nanoplate EISOI (electrolyte-insulator-silicon-on-insulator) capacitive biosensors on the same SOI chip as well as differential-mode measurements. The feasibility of the proposed approach has been demonstrated by realizing sensors for the pH and penicillin concentration detection as well as for the label-free electrical monitoring of polyelectrolyte multilayers formation and DNA (deoxyribonucleic acid)-hybridization event. A potential change of ～ 120 mV has been registered after the DNA hybridization for the sensor immobilized with perfectly matched single-strand DNA, while practically no signal changes have been observed for a sensor with fully mismatched DNA. The realized examples demonstrate the potential of the nanoplate SOI capacitors as a new basic structural element for the development of different types of field-effect biosensors.     

Plume-tracking robots: a new application of chemical sensors

Many animals have the ability to search for odor sources by tracking their plumes. Some of the key features of this search behavior have been successfully transferred to robot platforms, although the capabilities of animals are still beyond the current level of sensor technologies. The examples described in this paper are (1) incorporating into a wheeled robot the upwind surges and casting used by moths in tracking pheromone plumes, (2) extracting useful information from the response patterns of a chemical sensor array patterned after the spatially distributed chemoreceptors of some animals, and (3) mimicking the fanning behavior of silkworm moths to enhance the reception of chemical signals by drawing molecules from one direction. The achievements so far and current efforts are reviewed to illustrate the steps to be taken toward future development of this technology.     

Urinary Colorimetric Sensor Array and Algorithm to Distinguish Kawasaki Disease from Other Febrile Illnesses

Objectives

Kawasaki disease (KD) is an acute pediatric vasculitis of infants and young children with unknown etiology and no specific laboratory-based test to identify. A specific molecular diagnostic test is urgently needed to support the clinical decision of proper medical intervention, preventing subsequent complications of coronary artery aneurysms. We used a simple and low-cost colorimetric sensor array to address the lack of a specific diagnostic test to differentiate KD from febrile control (FC) patients with similar rash/fever illnesses.

Study Design

Demographic and clinical data were prospectively collected for subjects with KD and FCs under standard protocol. After screening using a genetic algorithm, eleven compounds including metalloporphyrins, pH indicators, redox indicators and solvatochromic dye categories, were selected from our chromatic compound library (n = 190) to construct a colorimetric sensor array for diagnosing KD. Quantitative color difference analysis led to a decision-tree-based KD diagnostic algorithm.

Results

This KD sensing array allowed the identification of 94% of KD subjects (receiver operating characteristic [ROC] area under the curve [AUC] 0.981) in the training set (33 KD, 33 FC) and 94% of KD subjects (ROC AUC: 0.873) in the testing set (16 KD, 17 FC). Color difference maps reconstructed from the digital images of the sensing compounds demonstrated distinctive patterns differentiating KD from FC patients.

Conclusions

The colorimetric sensor array, composed of common used chemical compounds, is an easily accessible, low-cost method to realize the discrimination of subjects with KD from other febrile illness.     

Integrated Terahertz Surface Plasmon Resonance on Polyvinylidene Fluoride Layer for the Profiling of Fluid Reflectance Spectra

We design terahertz (THz) surface-plasmon-resonance (SPR) sensors using a ferroelectric polyvinylidene fluoride (PVDF) thin layer for biological sensing. The reflectivity properties based on SPR are described using transfer matrix method (TMM) and numerically simulated using finite-difference time domain (FDTD) method. The sensing characteristics of the structure are systematically analyzed through the examination of the reflectivity spectrum. The results reveal that the pronounced SPR resonance peak has quasi-linear relationship with the refractive index variation of the material under investigation. Through analyzing and optimizing the structural parameters of the THz SPR sensor, we achieved the theoretical value of the refractive index detection sensitivity as high as 0.393 THz/unit change of refractive index (RIU) for a 20-μm-thick liquid sample with a 10-μm PVDF layer. This work shows great promise toward realizing a THz SPR sensor with high sensitivity for identifying the signatures of biological fluid sample.     

Linking bacteriophage infection to quorum sensing signalling and bioluminescent bioreporter monitoring for direct detection of bacterial agents

AIM: To incorporate into the lambda phage genome, a luxI-based acyl-homoserine lactone (AHL) synthase genetic construct and exploit the autoamplified power of quorum sensing to translate a phage infection event into a chemical signature detectable by a lux-based bioluminescent bioreporter, with focus towards facile detection of microbial pathogens. METHODS AND RESULTS: The luxI gene from Vibrio fischeri was inserted into the lambda phage genome to construct a model phage-based biosensor system for the general detection of Escherichia coli. The AHL signalling molecules synthesized upon phage infection are detected by an AHL-specific bioluminescent bioreporter based on the luxCDABE gene cassette of V. fischeri. The assay generates target-specific visible light signals with no requisite addition of extraneous substrate. This binary reporter system was able to autonomously respond to lambda phage infection events at target E. coli concentrations ranging from 1 x 10(8) to 1 CFU ml(-1) within 1.5-10.3 h, respectively, in pure culture. When assayed against artificially contaminated lettuce leaf washings, detection within an E. coli inoculum range from 1 x 10(8) to 130 CFU ml(-1) was achieved within 2.6-22.4 h, respectively. CONCLUSIONS: The initial feasibility of binary phage-based reporter assays indicates that quorum sensing can be used to translate a phage infection event into an autoamplified chemical signature. SIGNIFICANCE AND IMPACT OF STUDY: With further modification, binary phage-based reporter assays may be capable of rapidly and cost effectively detecting pathogenic agents at very low population densities.     

Recent progress on performances and mechanisms of carbon dots for gas sensing

Carbon dots (CDs), as an attractive zero-dimensional carbon nanomaterial with unique photoluminescent merits, have recently exhibited significant application potential in gas sensing as a result of their excellent optical/electronic characteristics, high chemical/thermal stability, and tunable surface states. CDs exhibit strong light absorption in the ultraviolet range and tunable photoluminescence characteristics in the visible range, which makes CDs an effective tool for optical sensing applications. Optical gas sensor based on CDs have been investigated, which generally responds to the target gas by corresponding changes in optical absorption or fluorescence. Moreover, electrical gas sensor and quartz crystal microbalance sensor whose sensing layer involves CDs have also been designed. Electrical gas sensor exhibits an increase or a decrease in electrical current, capacitance, or conductance once exposed to the target gas. Quartz crystal microbalance sensor responds to the target gas with a frequency shift. CDs greatly promote the absorption of the target gas and improve the sensitivity of both sensors. In this review, we aim to summarize different types of gas sensors involving CDs, and sensing performances of these sensors for monitoring diverse gases or vapors, as well as the mechanisms of CDs in different types of sensors. Moreover, this review provides the prospect of the potential development of CDs based gas sensors.     

Sensitive chemical sensor array based on nanozymes for discrimination of metal ions and teas

Tea, originating from China, is an important part of Chinese traditional culture. There are different qualities of and producing areas for tea on the market, therefore it is necessary to discriminate between teas in a fast and accurate way. In this study, a chemical sensor array based on nanozymes was developed to discriminate between different metal ions and teas. The indicators for the sensor array are three kinds of nanozymes mimicking laccase (Cu‐ATP, Cu‐ADP, Cu‐AMP). The as‐developed sensor array successfully discriminated 12 metal ions and the detection limit was as low as 0.01 μM. The as‐developed sensor array was also able to discriminate tea samples. Different kinds of tea samples appeared in different areas in the canonical score plot with different response patterns. Furthermore, in a blind experiment, we successfully discriminated 12 samples with a 100% accuracy. This sensor array integrates chemistry and food science together, realizing the simultaneous detection of several kinds of teas using a sensitive method. The as‐developed sensor array would have an application in the tea market and provide a fast and easy method to discriminate between teas.     

A functional gene array for detection of bacterial virulence elements

Emerging known and unknown pathogens create profound threats to public health. Platforms for rapid detection and characterization of microbial agents are critically needed to prevent and respond to disease outbreaks. Available detection technologies cannot provide broad functional information about known or novel organisms. As a step toward developing such a system, we have produced and tested a series of high-density functional gene arrays to detect elements of virulence and antibiotic resistance mechanisms. Our first generation array targets genes from Escherichia coli strains K12 and CFT073, Enterococcus faecalis and Staphylococcus aureus. We determined optimal probe design parameters for gene family detection and discrimination. When tested with organisms at varying phylogenetic distances from the four target strains, the array detected orthologs for the majority of targeted gene families present in bacteria belonging to the same taxonomic family. In combination with whole-genome amplification, the array detects femtogram concentrations of purified DNA, either spiked in to an aerosol sample background, or in combinations from one or more of the four target organisms. This is the first report of a high density NimbleGen microarray system targeting microbial antibiotic resistance and virulence mechanisms. By targeting virulence gene families as well as genes unique to specific biothreat agents, these arrays will provide important data about the pathogenic potential and drug resistance profiles of unknown organisms in environmental samples.     

A composite sensor array impedentiometric electronic tongue Part II. Discrimination of basic tastes

An impedentiometric electronic tongue based on the combination of a composite sensor array and chemometric techniques aimed at the discrimination of soluble compounds able to elicit different gustative perceptions is presented. A composite array consisting of chemo-sensitive layers based on carbon nanotubes or carbon black dispersed in polymeric matrices and doped polythiophenes was used. The electrical impedance of the sensor array was measured at a frequency of 150 Hz by means of an impedance meter. The experimental set-up was designed in order to allow the automatic selection of a test solution and dipping of the sensor array following a dedicated measurement protocol. Measurements were carried out on 15 different solutions eliciting 5 different tastes (sodium chloride, citric acid, glucose, glutamic acid and sodium dehydrocholate for salty, sour, sweet, umami and bitter, respectively) at 3 concentration levels comprising the human perceptive range. In order to avoid over-fitting, more than 100 repetitions for each sample were carried in a 4-month period. Principal component analysis (PCA) was used to detect and remove outliers. Classification was performed by linear discriminant analysis (LDA). A fairly good degree of discrimination was obtained.     

Chirality Switching Via Rotation of Bilayer Fourfold Meta-Structure

Chiral effects have been observed from the interaction of chiral plasmonics nanostructures with light. Such nanostructures enhance the chiral response of molecules and provide an ideal platform for biological and chemical sensing. Here, we investigate the chiral switching effects of an array of subwavelength nanostructures with a unit cell composed of four double-layered nanostrips arranged to be rotationally symmetric. We observe chiral switching leading to a change in circular dichroism (CD) signature when the mutual angle between the first and second layer increases from 0° to 90° with respect to each other. This mutual angle can be manipulated to switch the handedness of the nanostructure and cause a change in the outgoing light. We also investigated the field distribution of each mode when circularly polarized light is normally incident into the structure. These modes can be categorized into longitudinal and transverse modes depending on the orientation of their dipole moments. The mode studies clearly show the nature of each plasmonics mode.     

Directional movement of steinernematid nematodes in response to electrical current

Steinernematid nematodes are parasites that are important natural regulating agents of insect populations. The infective juvenile nematodes respond to a variety of stimuli that aid in survival and host finding. Host finding strategies among steinernematids differ along a continuum from ambush (sit & wait) to cruiser (search & destroy). In this paper we describe directional movement in response to an electrical current, which was generated on agar plates. Specifically, Steinernema glaseri (a cruiser) moved to a higher electric potential, whereas Steinernema carpocapsae, an ambusher, moved to a lower electric potential. Thus, we hypothesize that steinernematids may detect electrical currents or electromagnetic fields in nature, and these stimuli may be used differentially among species for host finding or enhancing other fitness characters.