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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.
Light-stimulated hydrogel actuators with incorporated graphene oxide for microfluidic applications
(2015)
The chemical imaging sensor was applied to in-situ pH imaging of the solution in the vicinity of a corroding surface of stainless steel under potentiostatic polarization. A test piece of polished stainless steel was placed on the sensing surface leaving a narrow gap filled with artificial seawater and the stainless steel was corroded under polarization. The pH images obtained during polarization showed correspondence between the region of lower pH and the site of corrosion. It was also found that the pH value in the gap became as low as 2 by polarization, which triggered corrosion.
Abstractauthoren Graphene oxide (GO) nanoparticles were incorporated in temperature-sensitive Poly(N-isopropylacrylamide) (PNIPAAm) hydrogels. The nanoparticles increase the light absorption and convert light energy into heat efficiently. Thus, the hydrogels with GO can be stimulated spatially resolved by illumination as it was demonstrated by IR thermography. The temporal progression of the temperature maximum was detected for different concentrations of GO within the polymer network. Furthermore, the compatibility of PNIPAAm hydrogels with GO and cell cultures was investigated. For this purpose, culture medium was incubated with hydrogels containing GO and the viability and morphology of chinese hamster ovary (CHO) cells was examined after several days of culturing in presence of this medium.
The artificial olfactory image was proposed by Lundström et al. in 1991 as a new strategy for an electronic nose system which generated a two-dimensional mapping to be interpreted as a fingerprint of the detected gas species. The potential distribution generated by the catalytic metals integrated into a semiconductor field-effect structure was read as a photocurrent signal generated by scanning light pulses. The impact of the proposed technology spread beyond gas sensing, inspiring the development of various imaging modalities based on the light addressing of field-effect structures to obtain spatial maps of pH distribution, ions, molecules, and impedance, and these modalities have been applied in both biological and non-biological systems. These light-addressing technologies have been further developed to realize the position control of a faradaic current on the electrode surface for localized electrochemical reactions and amperometric measurements, as well as the actuation of liquids in microfluidic devices.
An acetoin biosensor based on a capacitive electrolyte–insulator–semiconductor (EIS) structure modified with the enzyme acetoin reductase, also known as butane-2,3-diol dehydrogenase (Bacillus clausii DSM 8716ᵀ), is applied for acetoin detection in beer, red wine, and fermentation broth samples for the first time. The EIS sensor consists of an Al/p-Si/SiO₂/Ta₂O₅ layer structure with immobilized acetoin reductase on top of the Ta₂O₅ transducer layer by means of crosslinking via glutaraldehyde. The unmodified and enzyme-modified sensors are electrochemically characterized by means of leakage current, capacitance–voltage, and constant capacitance methods, respectively.
α-hydroxy ketones (HK) and 1,2-diols are important building blocks for fine chemical synthesis. Here, we describe the R-selective 2,3-butanediol dehydrogenase from B. clausii DSM 8716ᵀ (BcBDH) that belongs to the metal-dependent medium chain dehydrogenases/reductases family (MDR) and catalyzes the selective asymmetric reduction of prochiral 1,2-diketones to the corresponding HK and, in some cases, the reduction of the same to the corresponding 1,2-diols. Aliphatic diketones, like 2,3-pentanedione, 2,3-hexanedione, 5-methyl-2,3-hexanedione, 3,4-hexanedione and 2,3-heptanedione are well transformed. In addition, surprisingly alkyl phenyl dicarbonyls, like 2-hydroxy-1-phenylpropan-1-one and phenylglyoxal are accepted, whereas their derivatives with two phenyl groups are not substrates. Supplementation of Mn²⁺ (1 mM) increases BcBDH's activity in biotransformations. Furthermore, the biocatalytic reduction of 5-methyl-2,3-hexanedione to mainly 5-methyl-3-hydroxy-2-hexanone with only small amounts of 5-methyl-2-hydroxy-3-hexanone within an enzyme membrane reactor is demonstrated.
Light-addressable potentiometric sensors for quantitative spatial imaging of chemical species
(2017)
A light-addressable potentiometric sensor (LAPS) is a semiconductor-based chemical sensor, in which a measurement site on the sensing surface is defined by illumination. This light addressability can be applied to visualize the spatial distribution of pH or the concentration of a specific chemical species, with potential applications in the fields of chemistry, materials science, biology, and medicine. In this review, the features of this chemical imaging sensor technology are compared with those of other technologies. Instrumentation, principles of operation, and various measurement modes of chemical imaging sensor systems are described. The review discusses and summarizes state-of-the-art technologies, especially with regard to the spatial resolution and measurement speed; for example, a high spatial resolution in a submicron range and a readout speed in the range of several tens of thousands of pixels per second have been achieved with the LAPS. The possibility of combining this technology with microfluidic devices and other potential future developments are discussed.
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.
Light-addressable potentiometric sensor as a sensing element in plug-based microfluidic devices
(2016)
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.
A high-Q resonance-mode measurement of EIS capacitive sensor by elimination of series resistance
(2017)
An EIS capacitive sensor is a semiconductor-based potentiometric sensor, which is sensitive to the ion concentration or pH value of the solution in contact with the sensing surface. To detect a small change in the ion concentration or pH, a small capacitance change must be detected. Recently, a resonance-mode measurement was proposed, in which an inductor was connected to the EIS capacitive sensor and the resonant frequency was correlated with the pH value. In this study, the Q factor of the resonant circuit was enhanced by canceling the internal resistance of the reference electrode and the internal resistance of the inductor coil with the help of a bypass capacitor and a negative impedance converter, respectively. 1% variation of the signal in the developed system corresponded to a pH change of 3.93 mpH, which was about 1/12 of the conventional method, suggesting a better performance in detection of a small pH change.
To study chemical and biological processes, spatially resolved determination of the concentrations of one or more analyte species is of distinct interest. With a light-addressable potentiometric sensor (LAPS), chemical images can be created, which visualize the concentration distribution above the sensor plate. One important challenge is to achieve a good lateral resolution in order to detect events that take place in a small and limited region. LAPS utilizes a focused light spot to address the measurement region. By moving this light spot along the semiconductor sensor plate, the concentration distribution can be observed. In this study, we show that utilizing a pulse as light excitation instead of a traditionally used continuously modulated light excitation, the lateral resolution can be improved by a factor of 6 or more.
The chemical imaging sensor is a semiconductor-based chemical sensor capable of visualizing pH and ion distributions. The spatial resolution depends on the lateral diffusion of photocarriers generated by illumination of the semiconductor substrate. In this study, two types of optical setups, one based on a bundle of optical fibers and the other based on a binocular tube head, were developed to project a hybrid illumination of a modulated light beam and a ring-shaped constant illumination onto the sensor plate. An improved spatial resolution was realized by the ring-shaped constant illumination, which suppressed lateral diffusion of photocarriers by enhanced recombination due to the increased carrier concentration.