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

Accepted Manuscript Title: Recent developments of chemical imaging sensor systems based on the principle of the light-addressable potentiometric sensor Author: id="aut0005" biographyid="vt0005" orcid="0000-0001-7993-716X"> Tatsuo Yoshinobu Ko-ichiro Miyamoto Torsten Wagner Michael J. Sch¨oning PII: DOI: Reference:

S0925-4005(14)01071-5 http://dx.doi.org/doi:10.1016/j.snb.2014.09.002 SNB 17378

To appear in:

Sensors and Actuators B

Received date: Revised date: Accepted date:

19-5-2014 11-8-2014 1-9-2014

Please cite this article as: T. Yoshinobu, K.-i. Miyamoto, T. Wagner, M.J. Sch¨oning, Recent developments of chemical imaging sensor systems based on the principle of the light-addressable potentiometric sensor, Sensors and Actuators B: Chemical (2014), http://dx.doi.org/10.1016/j.snb.2014.09.002 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Recent developments of chemical imaging sensor systems based on the principle of the light-addressable potentiometric sensor Tatsuo Yoshinobu1, Ko-ichiro Miyamoto2, Torsten Wagner3 and Michael J. Schöning3,4 1Department

of Biomedical Engineering,

2Department

of Electronic Engineering,

Tohoku University, 6-6-05 Aza-Aoba, Aramaki, Aoba-ku, Sendai 980-8579, Japan of Nano- and Biotechnologies, Aachen University of Applied Sciences,

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3Institute

Heinrich-Mußmann-Str. 1, 52428 Jülich, Germany 4Peter-Grünberg

Institute (PGI-8), Research Centre Jülich,

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54245 Jülich, Germany

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Abstract

The light-addressable potentiometric sensor (LAPS) is an electrochemical sensor with a the

measured

area

on

which

an

field-effect structure to detect the variation of the Nernst potential at its sensor surface, is

defined

by

illumination.

Thanks

to

this

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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

d

of reaction and diffusion in various electrochemical and biological samples. Recent developments of LAPS-based chemical imaging sensor systems, in terms of the spatial

Ac ce pt e

resolution, measurement speed, image quality, miniaturization and integration with microfluidic devices, are summarized and discussed. Keywords:

Chemical imaging sensor; Light-addressable potentiometric sensor; LAPS; Chemical sensor; Semiconductor; Field effect

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Introduction The ion-sensitive field-effect transistor (ISFET) [1,2] and the light-addressable potentiometric sensor (LAPS) [3-5] share much in common as for the sensing mechanism, but they also differ very much in the way the signal is read out [6-9]. As

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shown in Fig. 1, they both have a field-effect structure that consists of the stacking of the electrolyte – insulator – semiconductor, in which the insulator surface acts as the

sensing surface. In the case of the ISFET, a variation of the Nernst potential at the

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electrolyte – insulator interface changes the thickness and the conductance of the

inversion channel at the insulator – semiconductor interface by the field effect. The

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drain current therefore contains the information of the activity of the target ions binding to the sensing surface. In the case of the LAPS, a variation of the Nernst potential changes the thickness and the capacitance of the depletion layer

at the

an

insulator – semiconductor interface. When the semiconductor layer is illuminated with a modulated light, electron – hole pairs are generated and separated by the electric field

M

of the depletion layer, which is represented by the ac current source simplified circuit model in Fig. 2(a). The photocurrent signal external circuit is a function of

in the

measured in the

, which responds to the total of the bias voltage and curve due to the variation

d

the Nernst potential. Figure 2(b) shows the shift of the

of the Nernst potential, which is a function of the concentration of the target ion in the

Ac ce pt e

solution

The light-addressability is the most important feature of the LAPS, as

explicitly stated in its name. The measured area on the sensing surface is defined by illumination, or more precisely, by photocarriers generated by illumination. By illuminating various positions on the sensing surface, as many sensing areas can be defined on the sensing surface of a single sensor plate. This unique feature immediately allows three different types of applications. Firstly, by partitioning a plurality of measurement areas on the sensing surface and using each of them as an independent sensor, a LAPS can serve as a multi-well sensor array that can handle a plurality of samples of the same kind [10, 11]. Secondly, by modifying each of the measurement areas with different sensing materials, a LAPS can serve as a multi-analyte sensor that can detect and measure a plurality of chemical species [9,12-17]. Thirdly, a LAPS can serve as a chemical imaging sensor that can visualize the two-dimensional distribution of a specific chemical species within the solution in contact with the sensing surface [17-19]. Based on these features, the LAPS and the chemical imaging sensor are

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expected to be useful for analysis of electrochemical systems and biological specimens. The former includes visualization and dynamic analysis of electrolysis, electrochemical deposition and corrosion processes. The latter includes detection of microorganisms, measurement of metabolic activities of living cells, visualization of tissue preparations and measurement of neural activities.

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In this paper, recent developments of the LAPS-based chemical imaging sensor systems are summarized in terms of the spatial resolution, measurement speed, image

Comparison with ISFET/CCD-based chemical imaging a

semiconductor

device

that

was

developed

in

us

As

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quality, miniaturization and application to microfluidic devices.

analogy

to

a

metal-oxide-semiconductor field-effect transistor (MOSFET), a large-scale integration of the ISFET was a natural course of its development. An integrated ISFET array

an

functions as another type of a chemical imaging sensor [20-24]. A read-out mechanism similar to that of a charge coupled device (CCD) image sensor has been also proposed

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[25-27]. In this type of chemical imaging sensors, every pixel is realized by an independent sensor device structure, whereas a pixel in a LAPS-based chemical imaging sensor is defined by an illumination.

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The ISFET/CCD-based chemical imaging sensor has following advantages. Firstly, a large-scale and high-density array of sensors can be prepared with the help of

Ac ce pt e

the mature complementary MOS (CMOS) technology except for the sensing layer on top, which must be both sensitive to the target ions and resistant to chemicals. Secondly, the peripheral circuits such as amplifiers, analog-to-digital (AD) converters, memories and the communication interface can be integrated on chip, which allows a fast read-out of the signal. High frame rates of 100 frames per second (fps) and 333 fps have been reported for 64 × 64 and 16 × 16 ISFET arrays, respectively [23,24]. The disadvantages of the ISFET/CCD-based chemical imaging sensor are as follows. The number and positions of pixels are fixed at the time of fabrication. This may be a problem in certain biological applications where the location of the sample is unpredictable until it is cultured or captured on the sensing surface. The microfabrication process raises the fabrication costs and limits the size of the active area. In contrast, LAPS-based chemical imaging sensor systems have following advantages. Firstly, the LAPS sensor plate requires only an insulating layer and an ohmic contact formed on the front surface and the back surface, respectively, of the semiconductor substrate. It requires no device structures to be microfabricated and no wirings that need to be protected from the chemicals [28]. This is a great advantage in

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terms of the fabrication costs and the long-term stability. Also, the unnecessity of the microfabrication or photolithographic processes allows the whole wafer size to be employed as a single sensor plate, with which even large samples over a diameter of 10 inches can be measured. Secondly, pixels are not predefined and fixed by the sensor device structure. They can be freely defined by illumination after the sensor plate is

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fabricated, which allows a stepless zoom-in/zoom-out at the time of use. There is no limitation on the number of pixels, which is practically limited by the measurement time. The disadvantages of the LAPS-based chemical imaging sensor are as follows. It

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requires additional elements such as a light source, a focusing optics and a scanning

mechanism, which may hinder miniaturization of the system. The read-out is usually

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slow, especially in the case where a single light beam is used to scan the sensor plate in a pixel-by-pixel manner.

The LAPS-based chemical imaging sensor and the ISFET/CCD-based chemical

an

imaging sensor therefore have respective fields of suitable applications in which the

Improvement of the spatial resolution

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requirements are met better.

The spatial resolution is one of the most important properties of chemical

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imaging sensor systems [29-32]. The size of the measurement spot on the sensing surface is determined by the arrival of the minority carriers at the depletion layer,

Ac ce pt e

which depends on the size of the illuminated area and the lateral diffusion of minority carriers [33,34]. When the former is reduced by an appropriate optics, the latter remains the main factor.

Figure 3 shows the geometry of diffusion in the case of back-side illumination.

If the wavelength of the illumination is short and the penetration depth is small, the diffusion starts from the point of illumination on the back surface. The number of minority carriers arriving at the depletion layer with a lateral displacement of

is

smaller than those arriving at a point directly above the point of illumination by a factor of

where

is the thickness of the sensor plate and

carriers. This factor becomes

is the diffusion length of minority

at a lateral displacement of

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which shows the dependence of the spatial resolution on

and

.

It has been demonstrated that a higher spatial resolution could be obtained by thinning the active layer of the sensor plate [29]. The use of a silicon – on – insulator (SOI) structure [35] and a thin-film amorphous Si deposited on a glass substrate [36,37]

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have been reported as a method to realize a thin active layer and a high spatial

resolution. Another approach equivalent to thinning the active layer is to utilize a longer wavelength of light with a smaller value of the absorption coefficient

, which

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penetrates deeper into the semiconductor layer and generates photocarriers nearer to

At the extremes where the decay length in (2) will be

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the depletion layer [30]. or

, the spatial resolution given by

, which is a material parameter. The use of a thin-film as an active layer is therefore a prospective

an

amorphous Si with a small value of

choice, provided a stable insulating layer could be formed on it as a sensing layer.

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Our recent study by computer simulation [38-40] revealed that the distribution of the minority carriers arriving at the depletion layer was not the only factor that determines the spatial resolution of the LAPS-based chemical imaging sensor. When the

d

carrier concentration is raised too much at the point of illumination, it has an effect of reducing the local thickness of the depletion layer, which results in lowering of the

Ac ce pt e

spatial resolution. The optimal combinations of the parameters such as the wavelength and the intensity of the light, the doping concentration as well as

and

of the

semiconductor layer must be searched both by simulation [41-43] and experiments. High-speed measurement and movie recording The slow measurement speed has been one of the major problems of

LAPS-based chemical imaging sensor systems. In conventional systems, the chemical images were generated by measuring the photocurrent values at each position in a pixel-by-pixel manner [18]. In this case, the total time of measurement per image increased with the number of pixels. The highest modulation frequency used in a LAPS is usually of the order of several tens of kHz, and the measurement time per pixel is typically of the order of milliseconds to allow integration of the signal over at least several tens of cycles. When the measurement speed is 100 pixels per second, for example, it takes about 164 s and 655 s for an image with 128 × 128 and 256 × 256 pixels, respectively. Recently, Das et al. employed an analog micromirror for high-speed

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scanning and acquired an image of 200,000 pixels in 40 seconds [44]. Zhang et al. [45] proposed a method that drastically reduced the measurement time. A plurality of light beams modulated at different frequencies illuminate different locations within the sensing area. The resulting photocurrent signal in this case is a superposition of signals at different frequencies, each of which contains the information

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of the respective location. The individual signals can then be restored by a Fourier analysis [11,45-49].

This multiplicity has been increased up to 64, that means, the measurement

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can be carried out in parallel at 64 pixels [49]. The highest frame rate of 200 fps has

been realized so far by reducing the measurement time down to 5 ms. For separation of

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signals, the minimum frequency difference must be at least as large as the inverse of the measurement time, 200 Hz. In addition, the highest modulation frequency must be smaller than twice the lowest modulation frequency to avoid the interference of the

an

harmonics. The choice of the set of 64 frequencies would be, for example, 12.8, 13.0, 13.2 … 25.4 kHz. We used a bundle of 64 optical fibers that individually guided the emissions

M

from 64 LEDs [49] as shown in Fig. 4. The advantage of using a bundle of optical fibers is that the arrangement and spacing can be flexibly changed in formats other than 8 × 8 depending on the shape and the size of the sample to be measured. A high-frame-rate

d

movie recording of pH distribution could visualize the reaction and diffusion, for example, in a microfluidic channel.

Ac ce pt e

In addition to the high frame rate, a real-time observation of the

spatiotemporal change of the ion distribution is highly interesting. A data processing unit was developed with a field-programmable gate array (FPGA), which calculates in parallel the amplitude of each frequency component contained in the photocurrent signal. When frequency of

samples of the photocurrent signal are acquired at a sampling

and their values are

with a frequency of

, the amplitude of the signal

can be extracted by calculating

where summations for each

,

(3)

can be carried out in parallel during the sampling. With

the developed system, each frame could be generated only 10 μs after the completion of sampling. Image quality The quality of the chemical image depends on many factors and there are many tradeoff relationships among them. When the photocurrent value for a pixel is

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measured at a constant bias voltage, the noise level is dependent on the sampling number or the measurement time per pixel. If the measurement is not time-critical, the signal-to-noise ratio can be improved by increasing the sampling number. However, due to the nonlinearity of the transient part of the current – voltage curve in Fig. 2(b), the variation of the photocurrent at a constant bias voltage tends to saturate for a large

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variation of the Nernst potential. To correctly measure the variation of the Nernst potential without being influenced by the nonlinearity and saturation, the shift of the

current – voltage curve along the voltage axis can be directly measured by tracking the

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inflection point of the curve either by calculating the second derivative or by least-mean-square-fitting the transient part of the curve with a cubic function.

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In the case of imaging, the image quality is limited by the nonuniformity of the sensor plate rather than by the noise level in the photocurrent measurement. It was revealed that there were actually two types of nonuniformities [50]. The first type of

an

nonuniformity often appears as concentric stripes in a chemical image, which are attributed to defects in the semiconductor layer [51,52]. A higher recombination rate at

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the concentric defects results in the loss of photocarriers and decreases the photocurrent signal as shown in Fig. 5(a), which is observed as dark stripes in the photocurrent image. The second type of nonuniformity is caused by contamination of the sensing surface in

d

the course of its use, typically by absorption of ions which results in a flat-band voltage shift as shown in Fig. 5(b). The first type of nonuniformity can be corrected with a

Ac ce pt e

current calibration map, which describes the distribution of the height of the current – voltage curve. The second type of nonuniformity can be corrected with a voltage calibration map, which describes the distribution of the flat-band voltage or the horizontal displacement of the current – voltage curve. By preparing and updating these two calibration maps for the sensor plate, the two types of nonuniformities can be effectively corrected [50].

Another approach to improve the image quality is the phase-mode imaging

[53,54]. When the width and the capacitance of the depletion layer change in response to the Nernst potential, not only the amplitude but also the phase of the photocurrent signal changes. The phase of the photocurrent signal with respect to the modulation signal of a frequency

can be calculated by

(4) where

is the initial phase of the modulation signal. In contrast to the amplitude, the

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phase is not affected by the loss of photocarriers at defects or by the temporal fluctuation of the light intensity, and therefore, the phase-mode imaging is robust against such disturbances. Miniaturization

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As described earlier, the need for additional elements such as a focusing optics and a scanning mechanism was a problem in miniaturization of LAPS-based chemical imaging sensor systems. The use of an array of light sources is a solution to miniaturize

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the system, in which the light beam scans the back surface of the sensor plate without mechanical motion. The predefined arrangement of the light spots, however, invalidates

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one of the advantages of LAPS-based chemical imaging sensor systems, the flexibility in definition of measurement spots.

One example of an array-type light source is an LED array [48,49,55], which

an

already appeared in Fig. 4. In this case, each LED can be modulated at different frequencies for multiplexed measurements. The use of an optical fiber light guide

M

enables flexible definition of pixels [49]. The use of a micro-lens array to deliver a plurality of light beams onto the sensor plate has been also proposed [56]. The second example of an array of light sources is a display panel as shown in

d

Fig. 6(a). A similar approach has been already proposed for surface plasmon resonance imaging [57], in which a liquid crystal display (LCD) was employed for photo-excitation.

Ac ce pt e

For application to LAPS-based chemical imaging sensor systems, an organic light-emitting diode (OLED) panel is advantageous for its high contrast ratio, high density of pixels and the possibility of modulation at higher frequencies. With a 2-mm-thick panel placed in proximity to the back surface of the sensor plate, an active area of 20.1 mm × 13.2 mm could be scanned with a spacing of 200 μm between pixels [58,59].

The third example shown in Fig. 6(b) is the digital micromirror device (DMD)

known as a component for the digital light-processing (DLP) technology for video projectors [37,60-62]. A DMD consists of a microfabricated array of a huge number of micromirrors that can be individually flipped. With a DMD, it is possible to define a very large number of measurement spots on a single sensor plate. Although the pixel layout is fixed, the spacing between pixels on the sensor plate can be adjusted by projection. Integration with microfluidic devices Miniaturization and integration are implications of semiconductor-based

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sensors. Application of micromachining technology to a LAPS was proposed already in early literatures to form microchannels [10] and microchambers [63]. Especially, for biomedical applications, where the sample volume is typically small, integration of sensors with microfluidic devices is a prospective strategy. The combination of the LAPS-based chemical imaging sensor and a microfluidic device [49,64,65] has following

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advantages. Firstly, the sensor surface is flat and uniform, which facilitates the

construction of microchannels in arbitrary shapes. Secondly, the entire space within the microfluidic device will be measurable when constructed on the sensor surface, which

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offers the possibility of assays based on chemical imaging. Thirdly, by preparing a combined with optical imaging under microscope.

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microchannel with a transparent ceiling, the LAPS-based chemical imaging can be With chemical imaging, the concentration profile of the analyte along the flow direction in the microchannel as well as perpendicular to the flow can be recorded as a

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function of time, from which the dynamics of reaction and diffusion can be analyzed. Figure 7 illustrates two possible applications of chemical imaging in a microchannel.

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Figure 7(a) shows a schematic of a plug-based assay. A plug sample flows through a reaction zone, where a certain reaction is catalyzed, for example, with immobilized enzyme molecules, and the concentration profile of the analyte is continuously recorded.

d

In Fig. 7(b), the diffusion of a chemical species across the boundary of laminar flows is visualized, from which the diffusion coefficient can be calculated. As the diffusion

Ac ce pt e

coefficient of a chemical species is dependent on its molecular weight, this assay functions as a kind of mass-spectroscopic measurement of unknown molecules. New directions

In addition to improvements of the LAPS and the chemical imaging sensor,

there have also been proposals of new measurement principles and devices inspired by LAPS. For example, the use of semiconducting quantum dots immobilized on a gold surface was proposed as a light-controllable electrode for electrochemical sensing [66-68]. Whereas the lateral diffusion of photocarriers in a LAPS causes a problem of spatial resolution, quantum dots are separated from each other and therefore advantageous for higher resolution. Scanning photo-induced impedance microscopy (SPIM) [69,70] is an analogue of LAPS, in which the spatial distribution of the impedance is acquired. This is accomplished by collecting the photocurrent values under a bias voltage in the saturation region of the current – voltage curve in Fig. 2(b), instead of collecting the photocurrent values in the transition region as in the case of LAPS. Suzurikawa et al. proposed the light-addressable electrode (LAE) [71,72], which can

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locally stimulate cultured neurons or induce a localized electrochemical reaction using a device structure similar to that of LAPS. Functionalization of the sensing surface is another important field of research and development for widening applications of the LAPS and the chemical imaging sensor. Lee et al. demonstrated that a LAPS could be a platform for various types of

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biosensor assays [73]. Recent reports include application of LAPS to sensing ATP [74] and hybridization of DNAs [75,76].

Both improvement of the sensing system as a generic platform and

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development of the measurement system specialized for its particular use are essential

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for successful application of the LAPS-based chemical imaging sensor systems. Conclusion

The performance of LAPS-based chemical imaging sensor systems has been

an

drastically enhanced in the last twenty years in terms of the spatial resolution, measurement speed and image quality. There are many parameters to be taken into

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account in the design of the sensor, and there are many tradeoff relationships between them. Both simulations and experimental investigations are therefore important to further enhance the performance. When compared with ISFET/CCD-based systems,

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LAPS-based systems are generally slow, but both systems have particular advantages. For further applications, miniaturization and integration with microfluidic devices are

Ac ce pt e

key issues in addition to the enhancement of the sensor performance.

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[46] K. Miyamoto, Y. Kuwabara, S. Kanoh, T. Yoshinobu, T. Wagner and M. J. Schöning. "Chemical image scanner based on FDM-LAPS," Sensors and Actuators B, 137 (2009) 533-538.

[47] T. Wagner, C. F. B. Werner, K. Miyamoto, M. J. Schöning and T. Yoshinobu, "A high-density multi-point LAPS set-up using a VCSEL array and FPGA control,” Sensors and Actuators B 154 (2011) 124-128.

[48] A. Itabashi, N. Kosaka, K. Miyamoto, T. Wagner, M. J. Schöning and T. Yoshinobu, "High-speed chemical imaging system based on front-side-illuminated LAPS," Sensors and Actuators B 182 (2013) 315-321. [49] K. Miyamoto, A. Itabashi, T. Wagner, M. J. Schöning and T. Yoshinobu, "High-speed chemical imaging inside a microfluidic channel,” Sensors and Actuators B 194 (2014) 521-527. [50] K. Miyamoto, Y. Sugawara, S. Kanoh, T. Yoshinobu, T. Wagner and M. J. Schöning,

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Figure captions Comparison of the structures of (a) ISFET and (b) LAPS.

Fig. 2

(a) Simplified circuit model of the LAPS. (b) Shift of the current – voltage curve in response to the variation of the ion concentration.

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Fig. 1

Geometry of the carrier diffusion in the semiconductor layer.

Fig. 4

Bundle of optical fibers as a light guide to illuminate a plurality of locations.

Fig. 5

Two types of in-plane nonuniformities of the sensor plate, (a) reduction of the

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Fig. 3

photocurrent by loss of photocarriers at defects and (b) flat-band voltage shift. Array of light sources for a motionless scan of the sensor plate. (a) OLED display panel and (b) DMD. Fig.7

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Fig. 6

(a) Plug assay based on chemical imaging. (b) Diffusion of chemical species

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across the border between laminar flows.

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Biographies

Tatsuo Yoshinobu was born in Kyoto, Japan, in 1964. He received BE, ME, and PhD degrees in electrical engineering from Kyoto University in 1987, 1989, and 1992,

d

respectively, for his study on gas source molecular beam epitaxy of silicon carbide. In 1992, he joined the Institute of Scientific and Industrial Research, Osaka University,

Ac ce pt e

where he started the development of silicon-based chemical sensors. From 1999 to 2000, he was a guest scientist at the Research Centre Jülich, Germany. Since 2005, he is a professor for electronic engineering at Tohoku University, Sendai, Japan. Since 2008, he is also a professor at the Graduate School of Biomedical Engineering, Tohoku University.

Ko-ichiro Miyamoto was born in Yamaguchi, Japan, in 1979. He received BE, ME and PhD degrees from Tohoku University in 2002, 2004 and 2006, respectively. His PhD degree is for his study on the bio-molecular sensing using infrared absorption spectroscopy. Since 2006, he was an assistant professor at the Department of Electronic Engineering, Tohoku University and he was appointed as an associate professor in 2013. His research subject is on the application of silicon-based chemical sensors for bio-molecular sensing. Torsten Wagner was born in Mönchengladbach, Germany, in 1978. He received his diploma in 2003 in electrical engineering from the University of Applied Sciences

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Aachen, his master of science in 2003 in model simulation and control from the Coventry University in UK, and his doctoral degree (PhD) in 2008 from the Philips University Marburg in cooperation with the University of Applied Sciences Aachen. His research

subjects

concern

chemical

sensors,

especially

the

light-addressable

potentiometric sensor and sensor-signal processing. He received a scholarship

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(2008-2010) from the Japanese Society for the Promotion of Sciences (JSPS) to work at the Tohoku University in Japan, at which he became 2010 an assistant professor. In

December 2012, he went back to the University of Applied Sciences Aachen and started

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his own research group studying about the opto-switch light-addressable lab-on-chip

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based analysis platform.

Michael J. Schöning received his diploma degree in electrical engineering (1989) and his PhD in the field of semiconductor-based microsensors for the detection of ions in liquids

an

(1993), both from the Karlsruhe University of Technology. In 1989, he joined the Institute of Radiochemistry at the Research Centre Karlsruhe. Since 1993, he has been

M

with the Institute of Thin Films and Interfaces at the Research Centre Jülich, and since 1999 he was appointed as a full professor at Aachen University of Applied Sciences, Campus Jülich. Since 2006, he serves as a director of the Institute of Nano- and

d

Biotechnologies (INB) at the Aachen University of Applied Sciences. His main research subjects concern silicon-based chemical and biological sensors, thin-film technologies,

Ac ce pt e

solid-state physics, microsystem and nano(bio-)technology.

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ip t cr us an M d Ac ce pt e Fig. 1

Comparison of the structures of (a) ISFET and (b) LAPS.

Page 20 of 26

ip t cr us an M d Ac ce pt e Fig. 2

(a) Simplified circuit model of the LAPS. (b) Shift of the current – voltage curve in response to the variation of the ion concentration.

Page 21 of 26

ip t cr us an M d Ac ce pt e Fig. 3

Geometry of the carrier diffusion in the semiconductor layer.

Page 22 of 26

ip t cr us an M d Ac ce pt e Fig. 4

Bundle of optical fibers as a light guide to illuminate a plurality of locations.

Page 23 of 26

ip t cr us an M d Ac ce pt e Fig. 5

Two types of in-plane nonuniformities of the sensor plate, (a) reduction of the photocurrent by loss of photocarriers at defects and (b) flat-band voltage shift.

Page 24 of 26

ip t cr us an M d Ac ce pt e Fig. 6

Array of light sources for a motionless scan of the sensor plate. (a) OLED display panel and (b) DMD.

Page 25 of 26

ip t cr us an M d Ac ce pt e Fig.7

(a) Plug assay based on chemical imaging. (b) Diffusion of chemical species across the border between laminar flows.

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