A NOVEL BITTER DETECTION BIOSENSOR BASED ON LIGHT ADDRESSABLE POTENTIOMETRIC SENSOR

This paper presents a novel biosensor for bitter substance detection on the basis of light addressable potentiometric sensor(LAPS).Taste receptor cells(TRCs)were used as sensitive elements,which can respond to different bitter stimuli with extreme high sensitivity and speci-ficity.TRCs were isolated from the taste buds of rats and cultured on the surface of LAPS chip.Due to the unique advantages such as single-cell recording,light addressable capability,and noninvasiveness,LAPS chip was used as secondary transducer to monitor the responses of TRCs by recording extracelluar potential changes.The results indicate LAPS chip can effectively record the responses of TRCs to different bitter substances used in this study in a real-time manner for a long-term.In addition,by performing principal component analysis on the LAPS recording data,different bitter substances tested can be successfully discriminated.It is suggested this TRCs
LAPS hybrid biosensor could be a valuable tool for bitter substance detection.With further improvement and novel design,it has great potentials to be applied in both basic research and practical applications related to bitter taste detection.

Cell-Based Biosensors and Bio-MEMS for Its New Applications

This paper reviews a novel cell-based biosensor and Bio-MEMS which incorporate living cells as sensing elements that convert a change in immediate environment to signals conducive for processing.It is characterized with high sensitivity,excellent selectivity and fast response and have been implemented for a number of applications ranging from pharmaceutical screening to environmental pollutant detection.This paper also introduces our recent work about Light-Addressable Potentiometric Sensors (LAPS),Field Effect Transistor (FET),Micro-Electrode Array Sensors (MEAS) and Bio-MEMS for detecting the changes of concentration of extracellular ions and the action potential of living cell under effect of drugs and environmental parameters.Finely, the paper gives some prospects of cell-based biosensors in the future.

DESIGN OF MICROPHYSIOMETER BASED ON MULTIPARAMETER CELL-BASED BIOSENSORS FOR QUICK DRUG ANALYSIS

Cellular metabolism arouses the changes of substance in extracellular physiological microenvironment,and the metabolic level reflects the physiological state of cells.This paper developed a novel microphysiometer automatic analysis instrument based on multiparameter cell-based biosensors for quick drug analysis.This study included the multiparameter cell-based biosensors,cell culture chamber,drug auto-injection detection and analysis.The analysis instrument was capable of real-time detection for the acidic product and other chemical parameters generated by the cellular metabolism in the micro-volume.Finally,the paper employs human breast cancer cell line MCF-7 and drug experiments to verify the performance of microphysiometer,and study effects of different drugs on cell metabolism.Further,the research explores drug analysis method of the multiparameter microphysiometer.The results showed that the cell-based microphysiometer system provides a utility platform for rapid,long-term and automatic cell physiological environment detection and drug analysis.

A Novel Structure of LAPS Array for Cell-Based Biosensor

The light-addressable potentiometric sensor (LAPS) is a semiconductor-based cellular biosensor with an electrolyte-insulator-semiconductor (EIS) structure.By depositing biocompatible layers on the sensing surface for cell culture, it can be used to detect bioelectrical parameters of cells.The characteristic curve for photocurrent versus applied bias voltage to the system shows a current-voltage curve (Ⅰ-Ⅴcurve).This technique can be used to detect the action potential changes towards different drugs based on the bias voltage dependence of an optical current,and provides a dynamic system by scanning light beam at the very cell on the sensor device.The LAPS overcomes the limitation of recording sites,but high spatial resolution and sensitivity are also paramount.This paper discussed a novel structure of LAPS array for extracellular monitoring to decrease potential noise level.Both characteristics of active recording array areas and cell culture conditions are measured.

Sensing Escherichia coli O157:H7 via frequency shift through a self-assembled monolayer based QCM immunosensor

By means of the specific immuno-recognition and ultra-sensitive mass detection, a quartz crystal microbalance (QCM) biosensor for Escherichia coli O157:H7 detection was developed in this work. As a suitable surfactant, 16-mercaptohexadecanoic acid (MHDA) was introduced onto the Au surface of QCM, and then self-assembled with N-hydroxysuccinimide (NHS) raster as a reactive intermediate to provide an active interface for the specific antibody immobilization. The binding of target bacteria with the immobilized antibodies decreased the sensor’s resonant frequency, and the frequency shift was correlated to the bacterial concentration. The stepwise assembly of the immunosensor was characterized by means of the electrochemical techniques. Using the immersion-dry-immersion procedure, this QCM biosensor could detect 2.0×102 colony forming units (CFU)/ml E. coli O157:H7. In order to reduce the fabrication time, a polyelectrolyte layer-by-layer self-assembly (LBL-SA) method was adopted for fast construction. Finally, the reproducibility of this biosensor was discussed.

Peptide Functionalized Nanoplasmonic Sensor for Explosive Detection

In this study, a nanobiosensor for detecting explosives was developed, in which the peptide was synthesized with trinitrotoluene(TNT)-specific sequence and immobilized on nanodevice by Au–S covalent linkage, and the nanocup arrays were fabricated by nanoimprint and deposited with Au nanoparticles to generate localized surface plasmon resonance(LSPR). The device was used to monitor slight change from specific binding of 2,4,6-TNT to the peptide. With high refractive index sensing of ~10~4nm/RIU, the nanocup device can detect the binding of TNT at concentration as low as3.12×10^(-7)mg mL^(-1) by optical transmission spectrum modulated by LSPR. The nanosensor is also able to distinguish TNT from analogs of 2,4-dinitrotoluene and 3-nitrotoluene in the mixture with great selectivity. The peptide-based nanosensor provides novel approaches to design versatile biosensor assays by LSPR for chemical molecules.

A HYBRID ELECTRONIC NOSES’SYSTEM BASED ON MOS-SAW DETECTION UNITS INTENDED FOR LUNG CANCER DIAGNOSIS

In this paper,a hybrid electronic noses’system(HENS)based on MOS-SAW detection units intended for lung cancer diagnosis is proposed.The MOS gas sensors are used to detect the VOC molecules with low molecular weight(LMW),and the SAW sensors are adopted for the detection of VOC with high molecular weight(HMW).Thus,the novel combination of these two kinds of gas sensors provides higher sensitivities to more of VOC species in breath than that of using only a single kind of sensor.The signals from MOS-SAW detection units are then recognized by a multi-model diagnosis method.Applying four algorithms,six models were established for diagnosis and tested by leave-one-out cross-validation method.The model by artificial neural network(ANN)was selected as the best model to analyze breath samples.89 clinical samples were tested with MOS-SAW ANN diagnostic model,which takes the features derived from both the MOS and SAW sensors.It shows the highest sensitivity of 93.62%,and the highest selectivity of 83.37%.The study shows that,promisingly,our HENS is effective during screening of lung cancer patients,especially among the people of high risk.

THE STUDY ON NOVEL MICROELECTRODE ARRAY CHIPS FOR THE DETECTION OF HEAVY METALS IN WATER POLLUTION

Qualitative and quantitative analysis of trace heavy metals in aqueous environment are rapidly assuming significance along with the rapid development of industry.In this paper,gold microelectrode array(MEA)plated with mercury film was used for simultaneous voltammetric detection of zinc,cadmium,lead and copper ions in water.The electrochemical behavior and the actual surface area of the MEA were investigated by cyclic voltammetry in K_(3)[Fe(CN)_(6)].Electrochemical impedance spectrum(EIS)was utilized to examine the deposition of mercury on the electrode surface.Based on anodic stripping voltammetry,mercury film
Au MEA was applied to the detection of heavy metals in artificial analyte,where good calibrate linearity was obtained for cadmium,lead and copper ions,but with zinc exhibiting poor linearity.

A Heavy Metal Analysis Device Based on Light-addressable Potentiometric Sensor

<正>A full automatic device to detect heavy metal Hg,Fe,Cr elements based on thin-film sensitive materials prepared on surface of light-addressable potentiometric sensors (LAPS) by means of pulsed laser deposition PLD) technique is developed. High-purity chemical compound AgI:Ag_2S:HgI synthesized were used as target of PLD,thin film sensitive to Hg~ (2+) ion was prepared on the surface of LAPS.All-solide-state chalcogenide glass ion-selective electrodes ISE) ,Fe-ISE and Cr-ISE,were also used as targets of PLD,and thin-film sensors on different LAPS sensitive to Fe~ (3+) and Cr~ (6+) ions were prepared.The heavy metal analysis device with characteristics of collect sample in-site,real-time determination,communication and multifunction software were designed.Hardware design of the device mainly includes control and measurement aspects.The detected limits of Hg,Fe,Cr ions are 3.44×10~ (-7) mol/L,6.31×10~ (-6) mol/L and 2.09×10~ (-7) mol/L,respectively.

Automatic Monitoring Electronic Tongue with MEAs for Environmental Analysis

An automatic monitoring electronic tongue based on differential pulse stripping voltammetry (DPSV) was developed for heavy metals analysis.Simultaneous detections of trace Zn(Ⅱ),Cd(Ⅱ),Pb(Ⅱ),Cu(Ⅱ),Fe(Ⅲ) and Cr(Ⅲ) in water samples were performed with three electrochemical sensors.The sensor chip combined a silicon-based Hg-coated Au microelectrode array (MEA) as the working electrode on one side with an Ag/AgCl reference electrode and a Pt counter electrode on the other side.With a computer controlled multipotentiostat,pumps and valves,the electronic tongue realized in-situ real-time detection of the six metals mentioned above at parts-per-billion level without manual operation.

Neurochip Based on Light-addressable Potentiometric Sensor

<正>A novel neurochip based on light addressable potentiometric sensor (LAPS) is designed.Using its light addressable characteristic.The problems of the limitations of restricted discrete active sites of current neurochips,such as microelectrode array and field effect transistor array can be settled easily.Based on the theoretical analysis of the interface between cells and LAPS,spontaneously discharges of hippocampal neurons induced by Mg~ 2+)-free media treatment were recorded by LAPS.The results demonstrate that this kind of neurochip has potential to monitor electrophysiology of cultured cells in a non-invasive way.

Evaluating the efficacy and cardiotoxicity of EGFR-TKI AC0010 with a novel multifunctional biosensor

Non-small cell lung cancer(NSCLC)is a leading cause of cancer mortality worldwide.Although epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)have dramatically improved the life expectancy of patients with NSCLC,concerns about TKI-induced cardiotoxicities have increased.AC0010,a novel third-generation TKI,was developed to overcome drug resistance induced by EGFR-T790M mutation.However,the cardiotoxicity of AC0010 remains unclear.To evaluate the efficacy and cardiotoxicity of AC0010,we designed a novel multifunctional biosensor by integrating microelectrodes(MEs)and interdigital electrodes(IDEs)to comprehensively evaluate cell viability,electrophysiological activity,and morphological changes(beating of cardiomyocytes).The multifunctional biosensor can monitor AC0010-induced NSCLC inhibition and cardiotoxicity in a quantitative,label-free,noninvasive,and real-time manner.AC0010 was found to significantly inhibit NCI-H1975(EGFR-L858R/T790M mutation),while weak inhibition was found for A549(wild-type EGFR).Negligible inhibition was found in the viabilities of HFF-1(normal fibroblasts)and cardiomyocytes.With the multifunctional biosensor,we found that 10μM AC0010 significantly affected the extracellular field potential(EFP)and mechanical beating of cardiomyocytes.The amplitude of EFP continuously decreased after AC0010 treatment,while the interval decreased first and then increased.We analyzed the change in the systole time(ST)and diastole time(DT)within a beating interval and found that the DT and DT/beating interval rate decreased within 1 h after AC0010 treatment.This result probably indicated that the relaxation of cardiomyocytes was insufficient,which may further aggravate the dysfunction.Here,we found that AC0010 significantly inhibited EGFR-mutant NSCLC cells and impaired cardiomyocyte function at low concentrations(10μM).This is the first study in which the risk of AC0010-induced cardiotoxicity was evaluated.In addition,novel multifunctional biosensors can comprehensively evaluate the antitumor efficacy and cardiotoxicity of drugs and candidate compounds.

Artificial intelligence for brain disease diagnosis using electroencephalogram signals

Brain signals refer to electrical signals or metabolic changes that occur as a consequence of brain cell activity.Among the various non-invasive measurement methods,electroencephalogram(EEG)stands out as a widely employed technique,providing valuable insights into brain patterns.The deviations observed in EEG reading serve as indicators of abnormal brain activity,which is associated with neurological diseases.Brain‒computer interface(BCI)systems enable the direct extraction and transmission of information from the human brain,facilitating interaction with external devices.Notably,the emergence of artificial intelligence(AI)has had a profound impact on the enhancement of precision and accuracy in BCI technology,thereby broadening the scope of research in this field.AI techniques,encompassing machine learning(ML)and deep learning(DL)models,have demonstrated remarkable success in classifying and predicting various brain diseases.This comprehensive review investigates the application of AI in EEG-based brain disease diagnosis,highlighting advancements in AI algorithms.

Recentprogress in thebiomedical application of PEDOT:PSS hydrogels

Bioelectronics have gained substantial research attention owing to their potential applications in health monitoring and diagnose,and greatly promoted the development of biomedicine.Recently,poly(3,4-ethylenedioxythiophene):polystyrene sulfonate(PEDOT:PSS)hydrogels have arose as a promising candi-date for the next-generation bioelectronic interface due to its high-conductivity,versatility,flexibility and biocompatibility.In this review,we highlight the recent advances of PEDOT:PSS hydrogels,including the gelation methods and modification strategies,and summarize their wide applications in different type of sensors and tissue engineering in detail.We expect that this work will provide valuable information regarding the functionalizations and applications of PEDOT:PSS hydrogels.

The progress of olfactory transduction and biomimetic olfactory-based biosensors

Olfaction is a very important sensation for all animals. Recently great progress has been made in the research of olfactory transduction. Especially the novel finding of the gene superfamily encoding olfactory receptors has led to rapid advances in olfactory transduction. These advances also promoted the research of biomimetic olfactory-based biosensors and some obvious achievements have been obtained due to their potential commercial prospects and promising industrial applications. This paper briefly introduces the biological basis of olfaction, summarizes the progress of olfactory signal transduction in the olfactory neuron, the olfactory bulb and the olfactory cortex, outlines the latest devel- opments and applications of biomimetic olfactory-based biosensors. Finally, the olfactory biosensor based on light addressable potentiometric sensor (LAPS) is addressed in detail based on our recent work and the research trends of olfactory biosensors in future are discussed.

The Escherichia coli O157:H7 DNA detection on a gold nanoparticle-enhanced piezoelectric biosensor

This paper presents development of a quartz crystal microbalance (QCM) biosensor for real-time de- tection of E. coli O157:H7 DNA based on nanogold particles amplification. Many inner Au nanoparticles were immobilized onto the thioled surface of the Au electrode, then more specific thiolated sin- gle-stranded DNA (ssDNA) probes could be fixed through Au-SH bonding. The hybridization was in- duced by exposing the ssDNA probe to the complementary target DNA of E. coli O157:H7 gene eaeA, then resulted in a mass change and corresponding frequency shifts ( △f ) of the QCM. The outer avidin-coated Au nanoparticles could combine with the target DNA to increase the mass. The electro- chemical techniques, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were adopted to manifest and character each step. The target DNA corresponding to 2.0×103 colony forming unit (CFU)/mL E. coli O157:H7 cells can be detected by this biosensor, so it is practical to develop a sensitive and effective QCM biosensor for pathogenic bacteria detection based on specific DNA analy- sis. The piezoelectric biosensing system has potential for further applications, such as food safety and environment monitoring, and this approach lays the groundwork for incorporating the method into an integrated system for in-field bacteria detection.

Response enhancement of olfactory sensory neurons-based biosensors for odorant detection

This paper presents a novel strategy for the response enhancement of olfactory sensory neurons (OSNs)-based biosensors by monitoring the enhancive responses of OSNs to odorants. An OSNs-based biosensor was developed on the basis of the light addressable potentiometric sensor (LAPS), in which rat OSNs were cultured on the surface of LAPS chip and served as sensing elements. LY294002, the specific inhibitor of phosphatidylinositol 3-kinase (PI3K), was used to enhance the responses of OSNs to odorants. The responses of OSNs to odorants with and without the treatment of LY294002 were recorded by LAPS. The results show that the enhancive effect of LY294002 was recorded efficiently by LAPS and the responses of this OSNs-LAPS hybrid biosensor were enhanced by LY294002 by about 1.5-fold. We conclude that this method can enhance the responses of OSNs-LAPS hybrid biosensors, which may provide a novel strategy for the bioelectrical signal monitor of OSNs in biosensors. It is also suggested that this strategy may be applicable to other kinds of OSNs-based biosensors for cellular activity detection, such as microelectrode array (MEA) and field effect transistor (FET).

Microelectrode Recording of Tissue Neural Oscillations for a Bionic Olfactory Biosensor

In olfactory research, neural oscillations exhibit excellent temporal regularity, which are functional and necessary at thephysiological and cognitive levels. In this paper, we employed a bionic tissue biosensor which treats intact epithelium as sensing element to record the olfactory oscillations extracellularly. After being stimulated by odorant of butanedione, the olfactory receptor neurons generated different kinds of oscillations, which can be described as pulse firing oscillation, transient firing oscillation, superposed firing oscillation, and sustained firing oscillation, according to their temporal appearances respectively. With a time-frequency analysis of sonogram, the oscillations also demonstrated different frequency properties, such as δ, θ, α, β and γ oscillations. The results suggest that the bionic biosensor cooperated with sonogram analysis can well improve the in- vestigation of olfactory oscillations, and provide a novel model for artificial olfaetion sensor design.

A non-labeled DNA biosensor based on light addressable potentiometric sensor modified with TiO_2 thin film

Titanium dioxide (TiO2) thin film was deposited on the surface of the light addressable potentiometric sensor (LAPS) to modify the sensor surface for the non-labeled detection of DNA molecules. To evaluate the effect of ultraviolet (UV) treatment on the silanization level of TiO2 thin film by 3-aminopropyltriethoxysilane (APTS),fluorescein isothiocyanate (FITC) was used to label the amine group on the end of APTS immobilized onto the TiO2 thin film. We found that,with UV irradiation,the silanization level of the irradiated area of the TiO2 film was improved compared with the non-irradiated area under well-controlled conditions. This result indicates that TiO2 can act as a coating material on the biosensor surface to improve the effect and efficiency of the covalent immobilization of biomolecules on the sensor surface. The artificially synthesized probe DNA molecules were covalently linked onto the surface of TiO2 film. The hybridization of probe DNA and target DNA was monitored by the recording of I-V curves that shift along the voltage axis during the process of reaction. A significant LAPS signal can be detected at 10 μmol/L of target DNA sample.

Spatiotemporal coding of natural odors in the olfactory bulb

Smell that exists in the natural environment is composed of numerous odor molecules(Bushdid et al.,2014).The mammalian olfactory system can accurately identify environmental olfactory cues,including those related to food selection,recognition of conspecifics/predators,and emotional responses.