Light-addressable Potentiometric Sensor Research Articles

Light-Addressable Potentiometric Sensor as a Sensing Element in Plug-Based Microfluidic Devices.

A plug-based microfluidic system based on the principle of the light-addressable potentiometric sensor (LAPS) is proposed. The LAPS is a semiconductor-based chemical sensor, which has a free addressability of the measurement point on the sensing surface. By combining a microfluidic device and LAPS, ion sensing can be performed anywhere inside the microfluidic channel. In this study, the sample solution to be measured was introduced into the channel in a form of a plug with a volume in the range of microliters. Taking advantage of the light-addressability, the position of the plug could be monitored and pneumatically controlled. With the developed system, the pH value of a plug with a volume down to 400 nL could be measured. As an example of plug-based operation, two plugs were merged in the channel, and the pH change was detected by differential measurement.

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.

Influences of Probe’s Morphology for Metal Ion Detection Based on Light-Addressable Potentiometric Sensors

The sensing mechanism of binding Hg2+ into thymine-thymine (T-T) mismatched base pairs was introduced into a light-addressable potentiometric sensor (LAPS) with anti-Hg2+ aptamer as the sensing units. Three kinds of T-rich single-strand DNA (ssDNA) chains with different spacer lengths, from 0 to 12 –CH2 groups, were designed to investigate surface charge and morphological effects on the LAPS’ output. First, by comparing the responding of LAPS modified with three kinds of ssDNA, it was found that the best performance for Hg2+ sensing was exhibited by the probe without –CH2 groups. The detection limit of Hg2+ ion was 1 ppt under the optimal condition. Second, the cooperative effects of surface charge and morphology on the output were observed by the controlled experiments. The two effects were the negative charge balanced by metal cations and the morphological changing caused by the formation of T-Hg2+-T structure. In conclusion, not only the influences of the aptamer probe’s morphology and surface charge was investigated on the platform of LAPS, but also sensing Hg2+ ions was achieved for the first time by the presented aptamer LAPS.

Application of electroosmotic micropumps to a microfluidic system combined with a light‐addressable potentiometric sensor

An on‐chip electroosmotic (EO) micropump (EOP) was embedded in a microchannel combined with a light‐addressable potentiometric sensor (LAPS). The flow direction and the flow rate of EO flows on the LAPS chip could be controlled by the polarity and the magnitude of the applied DC voltage. The EOP could be used as an actuator to generate a sample droplet of about 1 nL and to drive it to the sensing position of a LAPS. A design of a microfluidic system as a (bio‐)chemical analysis device for measuring a small volume of sample is proposed.

P-I-N amorphous silicon for thin-film light-addressable potentiometric sensors

Amorphous silicon (a-Si) has been approved for use as the semiconductor layer in a light-addressable potentiometric sensor (LAPS). A new device structure of niobium oxide (NbOx)/P-I-N amorphous silicon (a-Si) on ITO/glass is proposed for a thin film LAPS with the advantage of a high photovoltage. P-type, intrinsic and N-type a-Si layers are fabricated by plasma enhanced chemical vapor deposition (PECVD) with selective gas dopants on ITO/glass. A single NbOx layer is directly sputtered onto an a-Si substrate and is used as the pH sensing membrane. The temperatures for all of the processes used to manufacture this device are lower than 300°C, including the rapid thermal anneal (RTA) treatment, which is compatible with conventional fabrication processes for glass substrates in solar cells and thin film transistors. Based on the photovoltage versus gate bias characteristics in standard buffer solutions, the calculated pH sensitivity and linearity from pH 2 to 10 is 40mV/pH and 99.4% for the P-I-N a-Si LAPS with RTA treatment at 300°C. Compared with an intrinsic a-Si structure, a 50% higher photovoltage is achieved in the P-I-N a-Si LAPS. Furthermore, XRD and SIMS are used to verify the properties of the a-Si film. A high frequency ac laser signal of up to 20kHz was obtained with the P-I-N a-Si LAPS while maintaining the same spatial resolution, which is important for two-dimensional images acquired by high-speed scanning with an analog micromirror.

Determination of the extracellular acidification of Escherichia coli K12 with a multi‐chamber‐based LAPS system

On‐line monitoring of the metabolic activity of microorganisms involved in intermediate stages of biogas production plays an important role to avoid undesirable “down times” during the biogas production. In order to control this process, an on‐chip differential measuring system based on the light‐addressable potentiometric sensor (LAPS) principle combined with a 3D‐printed multi‐chamber structure has been realized. As a test microorganism, Escherichia coli K12 (E. coli K12) were used for cell‐based measurements. Multi‐chamber structures were developed to determine the metabolic activity of E. coli K12 in suspension for a different number of cells, responding to the addition of a constant or variable amount of glucose concentrations, enabling differential and simultaneous measurements.Multi‐chamber differential measurement setup based on the LAPS principle; RE, reference electrode.

Highly sensitive covalently functionalized light-addressable potentiometric sensor for determination of biomarker

A biomarker is related to the biological status of a living organism and shows great promise for the early prediction of a related disease. Herein we presented a novel structured light-addressable potentiometric sensor (LAPS) for the determination of a model biomarker, human immunoglobulin G (hIgG). In this system, the goat anti-human immunoglobulin G antibody was used as recognition element and covalently immobilized on the surface of light-addressable potentiometric sensor chip to capture human immunoglobulin G. Due to the light addressable capability of light-addressable potentiometric sensor, human immunoglobulin G dissolved in the supporting electrolyte solution can be detected by monitoring the potential shifts of the sensor. In order to produce a stable photocurrent, the laser diode controlled by field-programmable gate array was used as the light emitter to drive the light-addressable potentiometric sensor. A linear correlation between the potential shift response and the concentration of human immunoglobulin G was achieved and the corresponding regression equation was ΔV (V)=0.00714ChIgG (μg/mL)–0.0147 with a correlation coefficient of 0.9968 over a range 0–150μg/mL. Moreover, the light-addressable potentiometric sensor system also showed acceptable stability and reproducibility. All the results demonstrated that the system was more applicable to detection of disease biomarkers with simple operation, multiple-sample format and might hold great promise in various environmental, food, and clinical applications.

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.

Research on the enhancement of signal-to-noise ratio of light-addressable potentiometric sensor by optical focusing

For enhancing the response of light-addressable potentiometric sensor (LAPS) and further improving its signal- to-noise ratio (SNR), an optical focusing method is adopted. Experimental research and theoretical analysis reveal that the magnitude of responsive signal is increased by optical focusing, and the SNR is improved remarkably. These research results indicate that the optical focusing is an effective approach for improving SNR of LAPS.

光寻址电位传感器的噪声分析与信号处理方法研究

光寻址电位传感器的噪声分析与信号处理方法研究

The detection of Escherichia coli (E. coli) with the pH sensitive hydrogel nanofiber-light addressable potentiometric sensor (NF-LAPS)

We report a simple, rapid and cost effective detection technique for Escherichia coli (E. coli) using a Light Addressable Potentiometric Sensor integrated with electrospun poly acrylic acid/polyvinyl alcohol (PAA/PVA) hydrogel nanofibers as a sensing layer (NF-LAPS). Changes in pH of the media are detected as E. coli cells ferment sugar molecules and increase acidity of the surrounding. A super-Nernstian response of a 74mV/pH change in the NF-LAPS provides high sensitivity towards E. coli with a theoretical limit of detection (LOD) of 20CFU/ml. The high sensitivity is associated with the pH sensitive behavior of the NFs on the surface. Detection of acidic species released in cellular metabolism of pathogens in the presence of carbon source renders the sensing mechanism cheaper, less time consuming and more practical than the antibody-antigen interaction based approach. Selectivity towards E. coli for applications in drinking water detection is ensured by the incorporation of d-mannose for specific binding.

"Click" Patterning of Self-Assembled Monolayers on Hydrogen-Terminated Silicon Surfaces and Their Characterization Using Light-Addressable Potentiometric Sensors.

Two potential strategies for chemically patterning alkyne-terminated self-assembled monolayers (SAMs) on oxide-free silicon or silicon-on-sapphire (SOS) substrates were investigated and compared. The patterned surfaces were validated using a light-addressable potentiometric sensor (LAPS) for the first time. The first strategy involved an integration of photolithography with "click" chemistry. Detailed surface characterization (i.e. water contact angle, ellipsometry, AFM, and XPS) and LAPS measurements showed that photoresist processing not only decreases the coverage of organic monolayers but also introduces chemically bonded contaminants on the surfaces, thus significantly reducing the quality of the SAMs and the utility of "click" surface modification. The formation of chemical contaminants in photolithography was also observed on carboxylic acid- and alkyl-terminated monolayers using LAPS. In contrast, a second approach combined microcontact printing (μCP) with "click" chemistry; that is azide (azido-oligo(ethylene glycol) (OEG)-NH2) inks were printed on alkyne-terminated SAMs on silicon or SOS through PDMS stamps. The surface characterization results for the sample printed with a flat featureless PDMS stamp demonstrated a nondestructive and efficient method of μCP to perform "click" reactions on alkyne-terminated, oxide-free silicon surfaces for the first time. For the sample printed with a featured PDMS stamp, LAPS imaging showed a good agreement with the pattern of the PDMS stamp, indicating the successful chemical patterning on non-oxidized silicon and SOS substrates and the capability of LAPS to image the molecular patterns with high sensitivity.

Fabrication of biocompatible lab‐on‐chip devices for biomedical applications by means of a 3D‐printing process

A new microfluidic assembly method for semiconductor‐based biosensors using 3D‐printing technologies was proposed for a rapid and cost‐efficient design of new sensor systems. The microfluidic unit is designed and printed by a 3D‐printer in just a few hours and assembled on a light‐addressable potentiometric sensor (LAPS) chip using a photo resin. The cell growth curves obtained from culturing cells within microfluidics‐based LAPS systems were compared with cell growth curves in cell culture flasks to examine biocompatibility of the 3D‐printed chips. Furthermore, an optimal cell culturing within microfluidics‐based LAPS chips was achieved by adjusting the fetal calf serum concentrations of the cell culture medium, an important factor for the cell proliferation.

Concept of photovoltaic transducer on a base of modified p–n junction solar cell

A concept of new photovoltaic transducer, combining properties of planar p–n solar cell and light-addressable potentiometric sensor (LAPS) is considered for chemical sensor application. The proposed photovoltaic transducer operation principle based on change of surface recombination velocity during gas adsorption. As compared with typical LAPS, the considered sensor has no reference electrode, it is not necessary to apply DC bias voltage and such sensor is applicable not only for liquid but for gas detection also. The influence of p–n junction depth, doping level, diffusion length on photocurrent of planar silicon junction for different value of surface recombination is studied by numerical simulation. It allows optimizing the junction parameters from point of view of its efficient application as a chemical sensor with photovoltaic transducer. The proposed chemical sensor concept was verified by LBIC method on modified industrial solar cell.

Light-addressable Potentiometric Sensor (LAPS) Combined with Multi-chamber Structures to Investigate the Metabolic Activity of Cells

LAPS are field-effect-based potentiometric sensors which are able to monitor analyte concentrations in a spatially resolved manner. Hence, a LAPS sensor system is a powerful device to record chemical imaging of the concentration of chemical species in an aqueous solution, chemical reactions, or the growth of cell colonies on the sensor surface, to record chemical images. In this work, multi-chamber 3D-printed structures made out of polymer (PP-ABS) were combined with LAPS chips to analyse differentially and simultaneously the metabolic activity of Escherichia coli K12 and Chinese hamster ovary (CHO) cells, and the responds of those cells to the addition of glucose solution.

Design of a miniaturized multisensor chip with nanoband electrode array and light addressable potentiometric sensor for ion sensing

We present a novel miniaturized multisensor chip integrated with a nanoband electrode array (NEA) for lead and copper detection and a light addressable potentiometric sensor (LAPS) for pH sensing.

P-I-N Amorphous Silicon Light-Addressable Potentiometric Sensors for High-photovoltage Chemical Image

For higher photo signal of chemical image sensor, a new device structure of P-I-N amorphous silicon (a-Si) on ITO/glass is first applied in light-addressable potentiometric sensor (LAPS). Niobium oxide (NbOx) is used as pH sensing membrane. All processes of device are lower than 300oC, which are suitable for glass substrate. Based on photovoltage versus gate bias characteristics, calculated pH sensitivity and linearity between pH 2 to 10 is 40mV/pH and 99.4%, respectively. Compare to conventional intrinsic amorphous silicon structure, improvement on photocurrent, and spatial resolution are 50% and 15%, respectively. In the meantime, higher frequency of ac signal of laser up to 20kHz could be used for high speed scanning by means of red laser and analog micromirror scanning system.

Label-free detection of DNA using a light-addressable potentiometric sensor modified with a positively charged polyelectrolyte layer.

A multi-spot (16 spots) light-addressable potentiometric sensor (MLAPS) consisting of an Al-p-Si-SiO2 structure modified with a weak polyelectrolyte layer of PAH (poly(allylamine hydrochloride)) was applied for the label-free electrical detection of DNA (deoxyribonucleic acid) immobilization and hybridization by the intrinsic molecular charge for the first time. To achieve a preferentially flat orientation of DNA strands and thus, to reduce the distance between the DNA charge and MLAPS surface, the negatively charged probe single-stranded DNAs (ssDNA) were electrostatically adsorbed onto the positively charged PAH layer using a simple layer-by-layer (LbL) technique. In this way, more DNA charge can be positioned within the Debye length, yielding a higher sensor signal. The surface potential changes in each spot induced due to the surface modification steps (PAH adsorption, probe ssDNA immobilization, hybridization with complementary target DNA (cDNA), non-specific adsorption of mismatched ssDNA) were determined from the shifts of photocurrent-voltage curves along the voltage axis. A high sensor signal of 83 mV was registered after immobilization of probe ssDNA onto the PAH layer. The hybridization signal increases from 5 mV to 32 mV with increasing the concentration of cDNA from 0.1 nM to 5 μM. In contrast, a small signal of 5 mV was recorded in the case of non-specific adsorption of fully mismatched ssDNA (5 μM). The obtained results demonstrate the potential of the MLAPS in combination with the simple and rapid LbL immobilization technique as a promising platform for the future development of multi-spot light-addressable label-free DNA chips with direct electrical readout.

High-sensitivity light-addressable potentiometric sensors using silicon on sapphire functionalized with self-assembled organic monolayers

The use of self-assembled organic monolayers as the insulator in light-addressable potentiometric sensors (LAPS) is shown for the first time. Silicon on sapphire (SOS) substrates were modified with 1-octadecene or undecylenic acid. Experiments with a photoresist pattern as the model system showed the same good spatial resolution that was previously obtained with a conventional insulator on SOS, but also a significant improvement in the photocurrent contrast and therefore the sensitivity of LAPS. Surface potential imaging was validated by studying micropatterns of poly(allylamine hydrochloride) (PAH) and DNA on a PAH template using LAPS. The results showed that self-assembled organic monolayers provide an excellent, reproducible, ultrathin insulator for LAPS, which can be readily functionalized and used for high-sensitivity LAPS imaging and sensing.

Analog micromirror-LAPS for chemical imaging and zoom-in application

The light-addressable potentiometric sensor (LAPS) is a kind of semiconductor-based label-free sensor that is capable of visualizing two-dimensional distribution chemical concentrations above the sensor surface. This report presents a new scanning methodology for the LAPS-based chemical imaging sensor system where an analog micromirror combined with a laser was used as a flexible light-addressing platform. In this set-up, the scanning area and the scanning spatiotemporal resolution can be modified in a user-defined program in a personal computer. This new scanning method can provide a ‘zoom-in’ applicability to deliver high-resolution chemical images at a desired location. The entire surface of the sensor can be scanned within a few seconds to generate the initial low resolution image; then the area of interest can be selected and scanned with slow speed to produce an image with higher spatial information. The Photo-response-reference bias voltage characteristic, pH-sensitivity and also the chemical imaging of uniform pH buffer solutions are successfully demonstrated with this setup.