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 microfl...

Light-Addressable Potentiometric Sensors for Quantitative Spatial Imaging of Chemical Species

The light-addressable potentiometric sensor (LAPS) is an electrochemical sensor with a field-effect structure to detect the variation of the Nernst potential at its sensor surface, the measured area on which is defined by illumination. Thanks to this light-addressability, the LAPS can be applied to chemical imaging sensor systems, which can visualize the two-dimensional distribution of a particular target ion on the sensor surface. Chemical imaging sensor systems are expected to be useful for analysis of reaction and diffusion in various electrochemical and biological samples. Recent developments of LAPS-based chemical imaging sensor systems, in terms of the spatial resolution, measurement speed, image quality, miniaturization and integration with microfluidic devices, are summarized and discussed.

Recent developments of chemical imaging sensor systems based on the principle of the light-addressable potentiometric sensor

In this study, a high-speed chemical imaging system was developed for visualization of the interior of a microfluidic channel. A microfluidic channel was constructed on the sensor surface of the light-addressable potentiometric sensor (LAPS), on which the ion concentrations could be measured in parallel at up to 64 points illuminated by optical fibers. The temporal change of pH distribution inside the microfluidic channel was recorded at a maximum rate of 100 frames per second (fps). The high frame rate allowed visualization of moving interfaces and plugs in the channel even at a flow velocity of 111 mm/s, which suggests the feasibility of plug-based microfluidic devices for flow-injection analysis (FIA).

High-speed chemical imaging inside a microfluidic channel

Rapid and wide-range determination of Cd(II), Pb(II), Cu(II) and Hg(II) in fish tissues using light addressable potentiometric sensor

Metabolism is a common biological mechanism in living cells. Acidification plays an important role in cell metabolism, in which the extracellular pH change is used to indicate the vitality of cells. For extracellular detection of cell metabolic substances, light addressable potentiometric sensor (LAPS) has many advantages, such as high sensitivity, easy encapsulation, and convenient integration with microfluidic system for cell experiments. LAPS is a spatially resolved biochemical sensor based on field-effect. In this work, we present a microfluidic system integrated with LAPS for real-time extracellular acidification rate (ECAR) detection. The functions of traditional microphysiometer are achieved with simpler structure devices. Polydimethylsiloxane (PDMS) chamber was manufactured for cell culture, and microfluidic flow paths were used for medium and drug delivery. A bubble trap device was applied to eliminate air bubbles generated in microfluidics. Characteristic tests and cell metabolism experiments were carried out to determine the performance of LAPS by monitoring the pH change of hepatoma HepG2 cells. Glucose and doxorubicin were delivered to the cell chamber to verify the effects of the drug. The pH sensitivity of LAPS is 335.5 nA/pH at the working point in constant voltage mode. The ECAR of HepG2 cells was -48.53 mpH/min in normal glucose medium (25 mM), and it changed to -114.42 mpH/min in high glucose medium (125 mM) and -17.88 mpH/min under the effect of doxorubicin (10 μM). The results show that the microfluidic LAPS presents good performance in real-time detection of cell acidification and provides a convenient means of assessing cellular specificity of drugs. The modular structure and high expandability make the microfluidic LAPS has good potential in the application of organ-on-chip.

Microfluidic chip system integrated with light addressable potentiometric sensor (LAPS) for real-time extracellular acidification detection

The chemical imaging sensor is a semiconductor-based chemical sensor that can visualize the spatial distribution of specific ions on the sensing surface. The conventional chemical imaging system based on the light-addressable potentiometric sensor (LAPS), however, required a long time to obtain a chemical image, due to the slow mechanical scan of a single light beam. For high-speed imaging, a plurality of light beams modulated at different frequencies can be employed to measure the ion concentrations simultaneously at different locations on the sensor plate by frequency division multiplex (FDM). However, the conventional measurement geometry of back-side illumination limited the bandwidth of the modulation frequency required for FDM measurement, because of the low-pass filtering characteristics of carrier diffusion in the Si substrate. In this study, a high-speed chemical imaging system based on front-side-illuminated LAPS was developed, which achieved high-speed spatiotemporal recording of pH change at a rate of 70 frames per second.

High-speed chemical imaging system based on front-side-illuminated LAPS

High-resolution and high-speed chemical imaging sensor based on optical fiber array

The chemical imaging sensor is a Si-based chemical sensor that visualizes the spatial distribution of a specific ion in the solution contacted with the sensing surface. It is based on the principle of the lightaddressable potentiometric sensor (LAPS), in which a modulated light beam is used to read out the ion concentration in the form of photocurrent. Since the conventional chemical imaging sensor uses a scanning light beam for mapping the distribution of the ion concentration, the long scan time has been a problem for imaging in real time. For high-speed imaging, a plurality of light beams modulated at different frequencies can be employed to measure the ion concentrations simultaneously at different locations. Although a wide frequency bandwidth is required for high-speed imaging, the modulation frequency is limited due to the low-pass characteristics of carrier diffusion in the conventional setup, in which the back-side of the Si substrate is illuminated. In this study, a high-speed chemical imaging system based on front-side-illuminated LAPS was developed, which achieved imaging of pH distribution at 70 frames per second.

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7.2.5 High-speed Chemical Imaging System Based on Front-side-illuminated LAPS

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High-speed chemical imaging system based on front-side-illuminated LAPS

High-resolution and high-speed chemical imaging sensor based on optical fiber array

7.2.5 High-speed Chemical Imaging System Based on Front-side-illuminated LAPS

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