Light-addressable Potentiometric Sensor Surface Research Articles

Urease-modified LAPS: Two-dimensional dynamic detection of enzymatic reactions

• Urea-sensitive LAPS fabricated by a layer-by-layer self-assembly technique. • The enzymatic reactions are monitored dynamically in spatially resolved manner. • A method for the selection of monitoring windows based on threshold intersections. • The 2D images are more uniform and reduce demand for the number of pixel points. Light addressable potentiometric sensor (LAPS) is a semiconductor-based electrochemical sensor with flat surface structure and superior light addressability, making it an ideal platform for visualizing enzymatic reactions. However, it is hardly to observe the true process of reactions because a large amount of information unrelated to the enzymatic reaction, such as buffer diffusion caused by pH gradient, is contained in photocurrent images. In this study, urea-sensitive LAPS were obtained by immobilizing urease on the surface of LAPS with Si/SiO 2 /Si 3 N 4 structured using a layer-by-layer self-assembly technique and a method for the selection of enzymatic reaction monitoring windows based on threshold intersections is proposed to reduce the influence of non-enzymatic reaction factors. The overall performance of the urea-sensitive LAPS was excellent, with a sensitivity of 92.04 ± 4.04 mV/pC urea and a linearity of 99.16 % in the range of 1–20 mM. The mean square error of photocurrent images using this method is reduced by an order of magnitude compared to original images, which are more uniform and reduce the pixel demand. Our work provides a more complete assessment of urea-sensitive LAPS, and the proposed window selection method based on threshold intersections provides a viable method for dynamic monitoring of chemical images with high uniformity and high refresh rates.

Label-free detection of glypican-3 using reduced graphene oxide /polyetherimide/gold nanoparticles enhanced aptamer specific sensing interface on light-addressable potentiometric sensor

Glypican-3 (GPC3) protein is considered as an effective and specific biomarker for the accurate diagnosis of hepatocellular carcinoma (HCC), and there is a critical demand to construct strategies with shorter time, lower cost noise and higher sensitivity. In this study, a biosensor for label-free detection of GPC3 was prepared by modifying GPC3 aptamer (GPC3Apt) on the surface of Si-based light addressable potentiometric sensor (LAPS) chip modified by reduced graphene oxide/polyetherimide/gold nanoparticles (rGO/PEI/AuNPs). Among them, GPC3Apt with a low equilibrium dissociation constant was used as a biorecognition molecule to recognize and capture GPC3. The rGO/PEI/AuNPs decorated on the LAPS surface could enlarge the surface area for GPC3Apt immobilization and provide more active sites for GPC3Apt to bind effectively with the target GPC3. When a bias voltage was provided to the LAPS system, the forming GPC3-GPC3Apt complexs on the sensing interface of LAPS would cause the potential of the sensitive membrane surface to change and generate a corresponding offset response in photocurrent-voltage (I-V) curves. The potential shift and GPC3 concentration showed a good linear range from 0.1 to 100.0 μg/mL with a detection limit of 40.0 ng/mL (S/N = 3) and a sensitivity of 1.33638 mV/μg/mL. In addition, the LAPS detection system also has good specificity and stability, which can be used for the detection of GPC3 in spiked serum samples.

On-Sensor Cryopreservation of Adherent Cells in Lab-on-a-Chip Systems

Introduction Biochemical sensors are one of the essential tools for cell-based assays used in major research fields including drug discovery, cancer research, and immunology. Although significant efforts have been made to develop new technologies and tools, most existing systems in this field are still not suitable for “ready‐to‐use in-field” applications, as the cells inside the assay need vital parameters, such as oxygen, nutrients, and temperature and therefore will not survive during a transportation to an end user. Nevertheless, providing these parameters is not practicable during conventional transportation either. Those systems need to be assembled and prepared on-site, which often requires a cell culture laboratory setting and trained staff. Thus, there is an urgent need for preserving the whole optimized assay system to utilize them for concepts like “ready-to-use” or “on-demand-use”.Cryopreservation, the process of freezing and preserving the cells at sub-zero temperatures is a well-known technique for cell culturing. It could be one possible solution to solve the transportation and storage challenges in the fields mentioned above. However, freezing of adherent cells is more prone to the cell membrane damage and cell detachment, due to ice crystal formation and a mismatch in the linear thermal expansion between the frozen cell membrane and the rigid substrate [1]. Therefore, innovative methods and tools must be implemented to overcome these challenges.In this work, for the first time, the surface of a field-effect-based sensor was modified with flexible electrospun fibers to allow on-sensor cryopreservation. Furthermore, a protocol was developed to freeze and to thaw adherent cells in a microfluidic channel. Method The light-addressable potentiometric sensor (LAPS), a field-effect-based biochemical sensor, can detect the extracellular acidification of the cells due to its pH sensitive transducer layer (Ta2O5). The LAPS was fabricated as a structure of Al/p-Si/SiO2/Ta2O5 as described in ref. [2]. The sensor surface was modified with flexible polyethylene vinyl acetate (PEVA) fibers using an electrospinning method. The modified LAPS chip was then fixed to the underside of a bottomless microfluidic slide to form a miniaturized device (cryo-chip) (Figure 1(a) and (b)). A flexible polymer coverslip and a conventional LAPS were used as control samples. All samples were sterilized by 70% ethanol for one hour under aseptic conditions in a laminar flow cabinet to maintain the sterility. Chinese hamster ovary (CHO-K1) cells were adherently cultured inside the channels of the device with the mixture of Ham’s Nutrient Mixture F-12/Dulbecco’s Modified Eagle Medium (Ham’s F-12/DMEM, 1:2 mixture, pH 7) supplemented with 5% fetal calf serum (FCS), 100 U/ml penicillin and 100 mg/ml streptomycin. After the cell culture inside the channels were obtained for 48h under cell culture conditions in an incubator, the entire device was placed in a 3D-printed freezing container and frozen at -80oC using a cryoprotectant solution (90% fetal calf serum supplemented with 10% dimethyl sulfoxide). The samples were kept in the freezer overnight. The frozen device was then thawed rapidly by transferring them directly to the incubator (37oC). The cryoprotectant solution inside the channels was removed by washing with the fresh medium (37oC) four times, as soon as the ice crystals disappeared. Cell recovery and cell viability were analyzed before and after cryopreservation using a dye exclusion assay and a cell counting kit (CCK)-8 assay. In addition, as proof-of-concept measurements, the extracellular acidification of the cells was monitored by the LAPS chip, after the cryopreservation. Results and Conclusions The results showed that the sensor surface modified with the electrospun PEVA fibers exhibits enhanced biocompatibility, which promotes cell proliferation and spreading. In addition, the novel cryo-chip system using this hybrid structure (rigid/flexible) is effective compared to an un-modified LAPS surface for keeping cells viable during on-sensor cryopreservation. These findings showed, for the first time, that a cryopreservation on-chip is possible and that microfluidic systems including semiconductor based sensors can survive the cryopreservation treatment. Thus, this kind of cryo-chip systems enable on-sensor cryopreservation and measurement which can open up a new possibility for “ready-to-use, in field” applications. Being able to prepare the entire system at the manufacturing stage and to send them via a cold-chain transport further eliminate potential run-to-run and operator-to-operator variability, resulting in more reproducible results. Acknowledgements Dua Özsoylu (DÖ) would like to acknowledge the PhD research scholarship grant from Scientific and Technological Research Council of Turkey (TÜBITAK) under BIDEB 2214-A. The authors also gratefully thank the Federal Ministry of Education and Research of Germany (Opto-Switch FKZ: 13N12585). This study is a part of PhD thesis study of DÖ (thesis number DEU. HSI. PhD-2013970198) in Dokuz Eylül University, Institute of Health Sciences, Turkey.

A novel aptasensor based on light-addressable potentiometric sensor for the determination of Alpha-fetoprotein

In this work, a novel and simple aptasensor based on the light-addressable potentiometric sensor (LAPS) for Alpha-fetoprotein (AFP) detection was proposed. Due to the light addressable capability and potentiometric stability of LAPS, the concentration of AFP can be determined by monitoring the potential shifts of LAPS, which was caused by specific reaction between AFP-aptamer and AFP. The AFP-aptamer and gold nanoparticles (Au NPs) were modified on the surface of LAPS chip to fabricate the biological sensing element of LAPS system. The AFP-aptamer was used as molecules probe to recognize and capture AFP. Au NPs deposited on the LAPS surface could enlarge the surface area for the AFP-aptamer immobilization and provide more sites for AFP-aptamer to bind effectively with the target AFP and form more aptamer-antigen complex. Under optimal conditions, the potential shifts of the LAPS detection system were proportional to the AFP concentration in a wide linear range from 0.1–100 μg/mL. The regression equation is Y = 2.5892X+103.42778 (Y was the potential shift and X indicated the concentration of AFP) with a correlation coefficient of 0.9959 and a detection limit of 92.0 ng/mL at a signal-to-noise ratio of 3. The proposed method exhibited a good analytical performance and provided a promising potential application for aptasensor combined with LAPS in immunoassays.

Differential chemical imaging of extracellular acidification within microfluidic channels using a plasma-functionalized light-addressable potentiometric sensor (LAPS)

Extracellular acidification is a basic indicator for alterations in two vital metabolic pathways: glycolysis and cellular respiration. Measuring these alterations by monitoring extracellular acidification using cell-based biosensors such as LAPS plays an important role in studying these pathways whose disorders are associated with numerous diseases including cancer. However, the surface of the biosensors must be specially tailored to ensure high cell compatibility so that cells can represent more in vivo-like behavior, which is critical to gain more realistic in vitro results from the analyses, e.g., drug discovery experiments. In this work, O2 plasma patterning on the LAPS surface is studied to enhance surface features of the sensor chip, e.g., wettability and biofunctionality. The surface treated with O2 plasma for 30 s exhibits enhanced cytocompatibility for adherent CHO–K1 cells, which promotes cell spreading and proliferation. The plasma-modified LAPS chip is then integrated into a microfluidic system, which provides two identical channels to facilitate differential measurements of the extracellular acidification of CHO–K1 cells. To the best of our knowledge, it is the first time that extracellular acidification within microfluidic channels is quantitatively visualized as differential (bio-)chemical images.

On-Sensor Cryopreservation of Adherent Cells in Lab-on-a-Chip Systems

Introduction Biochemical sensors are one of the essential tools for cell-based assays used in major research fields including drug discovery, cancer research, and immunology. Although significant efforts have been made to develop new technologies and tools, most existing systems in this field are still not suitable for “ready‐to‐use in-field” applications, as the cells inside the assay need vital parameters, such as oxygen, nutrients, and temperature and therefore will not survive during a transportation to an end user. Nevertheless, providing these parameters is not practicable during conventional transportation either. Those systems need to be assembled and prepared on-site, which often requires a cell culture laboratory setting and trained staff. Thus, there is an urgent need for preserving the whole optimized assay system to utilize them for concepts like “ready-to-use” or “on-demand-use”.Cryopreservation, the process of freezing and preserving the cells at sub-zero temperatures is a well-known technique for cell culturing. It could be one possible solution to solve the transportation and storage challenges in the fields mentioned above. However, freezing of adherent cells is more prone to the cell membrane damage and cell detachment, due to ice crystal formation and a mismatch in the linear thermal expansion between the frozen cell membrane and the rigid substrate [1]. Therefore, innovative methods and tools must be implemented to overcome these challenges.In this work, for the first time, the surface of a field-effect-based sensor was modified with flexible electrospun fibers to allow on-sensor cryopreservation. Furthermore, a protocol was developed to freeze and to thaw adherent cells in a microfluidic channel. Method The light-addressable potentiometric sensor (LAPS), a field-effect-based biochemical sensor, can detect the extracellular acidification of the cells due to its pH sensitive transducer layer (Ta2O5). The LAPS was fabricated as a structure of Al/p-Si/SiO2/Ta2O5 as described in Ref. [2]. The sensor surface was modified with flexible polyethylene vinyl acetate (PEVA) fibers using an electrospinning method. The modified LAPS chip was then fixed to the underside of a bottomless microfluidic slide to form a miniaturized device (cryo-chip) (Figure 1(a) and (b)). A flexible polymer coverslip and a conventional LAPS were used as control samples. All samples were sterilized by 70% ethanol for one hour under aseptic conditions in a laminar flow cabinet to maintain the sterility. Chinese hamster ovary (CHO-K1) cells were adherently cultured inside the channels of the device with the mixture of Ham’s Nutrient Mixture F-12/Dulbecco’s Modified Eagle Medium (Ham’s F-12/DMEM, 1:2 mixture, pH 7) supplemented with 5% fetal calf serum (FCS), 100 U/ml penicillin and 100 mg/ml streptomycin. After the cell culture inside the channels were obtained for 48h under cell culture conditions in an incubator, the entire device was placed in a 3D-printed freezing container and frozen at -80oC using a cryoprotectant solution (90% fetal calf serum supplemented with 10% dimethyl sulfoxide). The samples were kept in the freezer overnight. The frozen device was then thawed rapidly by transferring them directly to the incubator (37oC). The cryoprotectant solution inside the channels was removed by washing with the fresh medium (37oC) four times, as soon as the ice crystals disappeared. Cell recovery and cell viability were analyzed before and after cryopreservation using a dye exclusion assay and a cell counting kit (CCK)-8 assay. In addition, as proof-of-concept measurements, the extracellular acidification of the cells was monitored by the LAPS chip, after the cryopreservation. Figure 1: Photos of the cryo-chip system for on-sensor cryopreservation. a) The modified LAPS chip integrated in a microfluidic chip system and its complementary connections; b) culturing of the CHO-K1 cells inside the channels on the LAPS surface, which are modified by electrospun PEVA fibers. Results and Conclusions The results showed that the sensor surface modified with the electrospun PEVA fibers exhibits enhanced biocompatibility, which promotes cell proliferation and spreading. In addition, the novel cryo-chip system using this hybrid structure (rigid/flexible) is effective compared to an un-modified LAPS surface for keeping cells viable during on-sensor cryopreservation. These findings showed, for the first time, that a cryopreservation on-chip is possible and that microfluidic systems including semiconductor based sensors can survive the cryopreservation treatment. Thus, this kind of cryo-chip systems enable on-sensor cryopreservation and measurement which can open up a new possibility for “ready-to-use, in field” applications. Being able to prepare the entire system at the manufacturing stage and to send them via a cold-chain transport further eliminate potential run-to-run and operator-to-operator variability, resulting in more reproducible results. Acknowledgements Dua Özsoylu (DÖ) would like to acknowledge the PhD research scholarship grant from Scientific and Technological Research Council of Turkey (TÜBITAK) under BIDEB 2214-A. The authors also gratefully thank the Federal Ministry of Education and Research of Germany (Opto-Switch FKZ: 13N12585). This study is a part of PhD thesis study of DÖ (thesis number DEU. HSI. PhD-2013970198) in Dokuz Eylül University, Institute of Health Sciences, Turkey.

Label-Free Detection of E. coli O157:H7 DNA Using Light-Addressable Potentiometric Sensors with Highly Oriented ZnO Nanorod Arrays.

The detection of bacterial deoxyribonucleic acid (DNA) is of great significance in the quality control of food and water. In this study, a light-addressable potentiometric sensor (LAPS) deposited with highly oriented ZnO nanorod arrays (NRAs) was used for the label-free detection of single-stranded bacterial DNA (ssDNA). A functional, sensitive surface for the detection of Escherichia coli (E. coli) O157:H7 DNA was prepared by the covalent immobilization of the specific probe single-stranded DNA (ssDNA) on the LAPS surface. The functional surface was exposed to solutions containing the target E. coli ssDNA molecules, which allowed for the hybridization of the target ssDNA with the probe ssDNA. The surface charge changes induced by the hybridization of the probe ssDNA with the target E. coli ssDNA were monitored using LAPS measurements in a label-free manner. The results indicate that distinct signal changes can be registered and recorded to detect the target E. coli ssDNA. The lower detection limit of the target ssDNA corresponded to 1.0 × 102 colony forming units (CFUs)/mL of E. coli O157:H7 cells. All the results demonstrate that this DNA biosensor, based on the electrostatic detection of ssDNA, provides a novel approach for the sensitive and effective detection of bacterial DNA, which has promising prospects and potential applications in the quality control of food and water.

Effect of Plasma Treatment on the Sensor Properties of a Light‐Addressable Potentiometric Sensor (LAPS)

A light‐addressable potentiometric sensor (LAPS) is a field‐effect‐based (bio‐) chemical sensor, in which a desired sensing area on the sensor surface can be defined by illumination. Light addressability can be used to visualize the concentration and spatial distribution of the target molecules, e.g., H+ ions. This unique feature has great potential for the label‐free imaging of the metabolic activity of living organisms. The cultivation of those organisms needs specially tailored surface properties of the sensor. O2 plasma treatment is an attractive and promising tool for rapid surface engineering. However, the potential impacts of the technique are carefully investigated for the sensors that suffer from plasma‐induced damage. Herein, a LAPS with a Ta2O5 pH‐sensitive surface is successfully patterned by plasma treatment, and its effects are investigated by contact angle and scanning LAPS measurements. The plasma duration of 30 s (30 W) is found to be the threshold value, where excessive wettability begins. Furthermore, this treatment approach causes moderate plasma‐induced damage, which can be reduced by thermal annealing (10 min at 300 °C). These findings provide a useful guideline to support future studies, where the LAPS surface is desired to be more hydrophilic by O2 plasma treatment.

Dual functional extracellular recording using a light-addressable potentiometric sensor for bitter signal transduction

This paper presents a dual functional extracellular recording biosensor based on a light-addressable potentiometric sensor (LAPS). The design and fabrication of this biosensor make it possible to record both extracellular membrane potential changes and ATP release from a single taste bud cell for the first time. For detecting ATP release, LAPS chip was functionalized with ATP-sensitive DNA aptamer by covalent immobilization. Taste bud cells isolated from rat were cultured on LAPS surface. When the desired single taste bud cell was illuminated by modulated light, ATP release from single taste bud cells can be measured by recording the shifts of bias voltage-photocurrent curves (I-V curves) when the LAPS chip is working in discrete mode. On the other hand, extracellular membrane potential changes can be monitored by recording the fluctuation of LAPS photocurrent when the LAPS chip is working in continuous mode. The results show this biosensor can effectively record the enhancive effect of the bitter substance and inhibitory effect of the carbenoxolone (CBX) on the extracellular membrane potential changes and ATP release of single taste bud cells. In addition, the inhibitory effect of CBX also confirms LAPS extracellular recordings are originated from bitter signal transduction. It is proved this biosensor is suitable for extracellular recording of ATP release and membrane potential changes of single taste bud cells. It is suggested this biosensor could be applied to investigating taste signal transduction at the single-cell level as well as applied to other types of cells which have similar functions to taste bud cells.

A Light-Addressable Potentiometric Sensor for Odorant Detection Using Single Bioengineered Olfactory Sensory Neurons as Sensing Element.

A light-addressable potentiometric sensor (LAPS), a silicon-based surface potential detector, is combined with bioengineered olfactory sensory neurons (OSN) for odorant detection. A LAPS chip is used as a transducer to monitor cell membrane potential changes. In addition, a focused movable laser with a diameter comparable to cell sizes is employed to select the desirable single cell for measurement under a microscope. Bioengineered OSNs are coupled to the LAPS surface and employed as sensing elements, which are prepared by the expression of an olfactory receptor of C. elegans, ODR-10, on the plasma membrane of rat primary OSNs via transient transfection. The responses of bioengineered OSNs to diacetyl, isoamyl acetate, and acetic acid are monitored by extracellular recording using the LAPS chip. Features of the recorded extracellular potential firings are analyzed in frequency and time domains. We have shown that bioengineered OSNs can generate specific response signals upon the stimulation of diacetyl, which is the natural ligand of ODR-10. Moreover, different concentrations of diacetyl can elicit different temporal firing patterns in bioengineered OSNs, which permits the concentration detection of specific odorant molecules in solution.

Light-addressable potentiometric sensor (LAPS) combined with magnetic beads for pharmaceutical screening

The light-addressable potentiometric sensor (LAPS) has the unique feature to address different regions of a sensor surface without the need of complex structures. Measurements at different locations on the sensor surface can be performed in a common analyte solution, which distinctly simplifies the fluidic set-up. However, the measurement in a single analyte chamber prevents the application of different drugs or different concentrations of a drug to each measurement spot at the same time as in the case of multi-reservoir-based set-ups. In this work, the authors designed a LAPS-based set-up for cell culture screening that utilises magnetic beads loaded with the endotoxin (lipopolysaccharides, LPS), to generate a spatially distributed gradient of analyte concentration. Different external magnetic fields can be adjusted to move the magnetic beads loaded with a specific drug within the measurement cell. By recording the metabolic activities of a cell layer cultured on top of the LAPS surface, this work shows the possibility to apply different concentrations of a sample along the LAPS measurement spots within a common analyte solution.

Sensing of double-stranded DNA molecules by their intrinsic molecular charge using the light-addressable potentiometric sensor

A multi-spot light-addressable potentiometric sensor (LAPS), which belongs to the family of semiconductor field-effect devices, was applied for label-free detection of double-stranded deoxyribonucleic acid (dsDNA) molecules by their intrinsic molecular charge. To reduce the distance between the DNA charge and sensor surface and thus, to enhance the electrostatic coupling between the dsDNA molecules and the LAPS, the negatively charged dsDNA molecules were electrostatically adsorbed onto the gate surface of the LAPS covered with a positively charged weak polyelectrolyte layer of PAH (poly(allylamine hydrochloride)). The surface potential changes in each spot of the LAPS, induced by the layer-by-layer adsorption of a PAH/dsDNA bilayer, were recorded by means of photocurrent-voltage and constant-photocurrent measurements. In addition, the surface morphology of the gate surface before and after consecutive electrostatic adsorption of PAH and dsDNA layers was studied by atomic force microscopy measurements. Moreover, fluorescence microscopy was used to verify the successful adsorption of dsDNA molecules onto the PAH-modified LAPS surface. A high sensor signal of 25mV was registered after adsorption of 10nM dsDNA molecules. The lower detection limit is down to 0.1nM dsDNA. The obtained results demonstrate that the PAH-modified LAPS device provides a convenient and rapid platform for the direct label-free electrical detection of in-solution hybridized dsDNA molecules.

Unlabeled multi tumor marker detection system based on bioinitiated light addressable potentiometric sensor

Multi biomarkers' assays are of great significance in clinical diagnosis. A label-free multi tumor markers' parallel detection system was proposed based on a light addressable potentiometric sensor (LAPS). Arrayed LAPS chips with basic structure of Si(3)N(4)-SiO(2)-Si were prepared on silicon wafers, and the label-free parallel detection system for this component was developed with user friendly controlling interfaces. Then the l-3,4-dihydroxyphenyl-alanine (L-Dopa) hydrochloric solution was used to initiate the surface of LAPS. The L-Dopa immobilization state was investigated by the theoretical calculation. L-Dopa initiated LAPS' chip was biofunctionalized respectively by the antigens and antibodies of four tumor markers, α-fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9) and Ferritin. Then unlabeled antibodies and antigens of these four biomarkers were detected by the proposed detection systems. Furthermore physical and measuring principles in this system were described, and qualitative understanding for experimental data were given. The measured response ranges were compared with their clinical cutoff values, and sensitivities were calculated by OriginLab. The results indicate that this bioinitiated LAPS based label-free detection system may offer a new choice for the realization of unlabeled multi tumor markers' clinical assay.

Bio-initiated light addressable potentiometric sensor for unlabeled biodetection and its MEDICI simulation

A bio-mimetic anchoring strategy based on L-3,4-dihydroxyphenylalanine (L-DOPA) was exploited to activate the surface of light addressable potentiometric sensor (LAPS), with the structure of Si(3)N(4)/SiO(2)/Si. X-Ray photoelectron spectroscopy (XPS) measurements were carried out to ascertain its existence. The protein's immobilization on L-DOPA-initiated LAPS were also tested by our LAPS system. Then L-DOPA-activated LAPS were applied in the unlabeled rabbit anti-mouse immunoglobulin (IgG) detection. The maximum sensitivity of L-DOPA-activated LAPS to antigen (Ag) is about 5.68 nA/p[Ag]. LAPS responses in IgG measurements were from 95 to 180 nA, when the concentration was varied from 0-4 μg mL(-1). These experiments show that L-DOPA is an available material for LAPS surface modifications. At the same time, simulations based on MEDICI (Synopsys™) were performed. The simulated curves are in accordance with experimental data which demonstrate our theoretical analysis for the experimental phenomenon, and indicate the feasibility of simulating biological electronic devices with MEDICI.

In vitro assessing the risk of drug-induced cardiotoxicity by embryonic stem cell-based biosensor

Drug-induced prolongation of ventricular repolarization with arrhythmia is a major concern in clinic safety pharmacology, and has been a common reason for the withdrawal of several promising drugs from the market. Therefore, novel techniques should be developed to evaluate cardiotoxicity of new drugs in preclinical research. A cardiomyocyte based biosensor was developed using the light addressable potentiometric sensor (LAPS). Mouse embryonic stem cells cultured on the surface of LAPS were induced to differentiate into synchronized spontaneity beating cardiomyocytes. Changes of extracellular potentials and cell shapes with their mechanical beatings could induce modulation of photocurrents in the LAPS system, and finally change the output of the sensor. With the characteristics of light addressability, LAPS can record cell clusters at any desired position. The sensor can be used to record the prolongation of ventricular action potentials with the cardiotoxicity induced by drugs such as amiodarone, levofloxacin, sparfloxacin, and noradrenaline. The quick and on time characteristics of the sensor were promising to establish a high-throughput platform for pharmacological toxicity investigation.

Olfactory receptor cells respond to odors in a tissue and semiconductor hybrid neuron chip

Olfactory systems of human beings and animals have the abilities to sense and distinguish varieties of odors. In this study, a bioelectronic nose was constructed by fixing biological tissues onto the surface of light-addressable potentiometric sensor (LAPS) to mimic human olfaction and realize odor differentiation. The odorant induced potentials on tissue–semiconductor interface was analyzed by sensory transduction theory and sheet conductor model. The extracellular potentials of the receptor cells in the olfactory epithelium were detected by LAPS. Being stimulated by different odorants, such as acetic acid and butanedione, olfactory epithelium activities were analyzed on basis of local field potentials and presented different firing modes. The signals fired in different odorants could be distinguished into different clusters by principal component analysis (PCA). Therefore, with cellular populations well preserved, the epithelium tissue and LAPS hybrid system will be a promising neuron chip of olfactory biosensors for odor detecting.

Light addressable potentiometric sensor array: A new approach for light beam positioning

An analytical system for multicomponent analysis of liquids based on a light addressable potentiometric sensor (LAPS) with an array of ion-sensitive polymer membranes is presented. A developed LAPS device is based on a BESOI wafer which permits easy fabrication of a sensor with thin silicon membrane and enhanced spatial resolution. To generate the photocurrent the backside silicon was illuminated using a new technical approach based on a DLP (Digital Light Processing) chip used in video projectors. When a DLP chip is coordinated with a digital graphic signal, a light source, and a projection lens, its mirrors can reflect a digital image onto the LAPS surface. The developed system is shown to be able to produce light spots down to 50 μm in diameter and perform measurements at different points with programmable coordinates. To prove the functionality of the proposed method a LAPS sensor array with 60 ion-sensitive membranes of three different types was tested.