CMOS image sensor-based implantable glucose sensor using glucose-responsive fluorescent hydrogel

Tokuda, Takashi; Takahashi, Motoki; Uejima, Kazuya; Masuda, Keita; Kawamura, Tatsuyuki; Ohta, Yasumi; Motoyama, Mayumi; Noda, Toshihiko; Sasagawa, Kiyotaka; Okitsu, Teru; Takeuchi, Shoji

doi:10.1364/boe.5.003859

Cited by 38 publications

(29 citation statements)

References 16 publications

(21 reference statements)

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“…At higher glucose concentrations (300–500 mg/dL), the nonlinear sensor response experienced a gradual declination in sensitivity and resolution (respectively to 8.4 fF(mg/dL) −1 and 0.35 mg/dL at 500 mg/dL) as an increasingly small number of binding sites remained available in the hydrogel. These sensor characteristics, appropriate for practical applications, are comparable to those of commercially available electrochemical sensors (e.g., 1 mg/dL over a glucose concentration range from 0 to 400 mg/dL 29, 30 or 500 mg/dL 31 ) as well as other research-stage boronic acid-based affinity sensors (e.g., 0.3 mg/dL 32 over a range from 0 to 300 mg/dL 33 or 540 mg/dL 34 ) for continuous glucose monitoring.…”

Section: Resultsmentioning

confidence: 57%

A hydrogel-based glucose affinity microsensor

Shang

Yan

Zhang

et al. 2016

Sensors and Actuators B: Chemical

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We present a hydrogel-based affinity microsensor for continuous glucose measurements. The microsensor is based on microelectromechanical systems (MEMS) technology, and incorporates a synthetic hydrogel that is attached to the device surface via in situ polymerization. Glucose molecules that diffuses into and out of the device binds reversibly with boronic acid groups in the hydrogel via affinity binding, and causes changes in the dielectric properties of the hydrogel, which can be measured using a MEMS capacitive transducer to determine the glucose concentration. The use of the in situ polymerized hydrogel eliminates mechanical moving parts found in other types of affinity microsensors, as well as mechanical barriers such as semipermeable membranes that are otherwise required to hold the glucose-sensitive material. This facilitates the miniaturization and robust operation of the microsensor, and can potentially improve the tolerance of the device, when implanted subcutaneously, to biofouling. Experimental results demonstrate that in a glucose concentration range of 0–500 mg/dL and with a resolution of 0.35 mg/dL or better, the microsensor exhibits a repeatable and reversible response, and can potentially be useful for continuous glucose monitoring in diabetes care.

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Section: Resultsmentioning

confidence: 57%

A hydrogel-based glucose affinity microsensor

Shang

Yan

Zhang

et al. 2016

Sensors and Actuators B: Chemical

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“…CMOS Image Sensors (CIS) [1][2][3], also called Active Pixel Sensors (APS), have become the main detector technology for optical imaging systems [1][2][3][4][5][6] in consumer and high-end scientific applications [4][5][6]. These optical sensors are exposed to harsh radiation environments in a wide variety of imaging applications (medical imaging [4][5][6][7], space remote sensing [8,9], nuclear power plant monitoring, inertial confinement fusion plasma diagnostics [10,11]). These radiation environments contain particles (e.g.…”

Section: Introductionmentioning

confidence: 99%

Pixel pitch and particle energy influence on the dark current distribution of neutron irradiated CMOS image sensors

et al. 2016

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The dark current produced by neutron irradiation in CMOS Image Sensors (CIS) is investigated. Several CIS with different photodiode types and pixel pitches are irradiated with various neutron energies and fluences to study the influence of each of these optical detector and irradiation parameters on the dark current distribution. An empirical model is tested on the experimental data and validated on all the irradiated optical imagers. This model is able to describe all the presented dark current distributions with no parameter variation for neutron energies of 14 MeV or higher, regardless of the optical detector and irradiation characteristics. For energies below 1 MeV, it is shown that a single parameter has to be adjusted because of the lower mean damage energy per nuclear interaction. This model and these conclusions can be transposed to any silicon based solid-state optical imagers such as CIS or Charged Coupled Devices (CCD). This work can also be used when designing an optical imager instrument, to anticipate the dark current increase or to choose a mitigation technique.

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“…Due to ultra-compactness and cost-effectiveness of the CMOS image sensor chips, implantable devices for the evaluations of biological information 2017) inside living bodies may be promising applications of contact fluorescence microscopy, particularly for brain research, 32,33 glucose monitoring, 34,35 and optical theranostics. 36 In conclusion, we have developed an on-chip cell analysis platform with the integration of contact fluorescence microscopy and microfluidics.…”

Section: Discussionmentioning

confidence: 99%

On-chip cell analysis platform: Implementation of contact fluorescence microscopy in microfluidic chips

et al. 2017

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Although fluorescence microscopy is the gold standard tool for biomedical research and clinical applications, their use beyond well-established laboratory infrastructures remains limited. The present study investigated a novel on-chip cell analysis platform based on contact fluorescence microscopy and microfluidics. Combined use of a contact fluorescence imager based on complementary metal-oxide semiconductor technology and an ultra-thin glass bottom microfluidic chip enabled both to observe living cells with minimal image distortion and to ease controlling and handling of biological samples (e.g. cells and biological molecules) in the imaged area. A proof-of-concept experiment of on-chip detection of cellular response to endothelial growth factor demonstrated promising use for the recently developed on-chip cell analysis platform. Contact fluorescence microscopy has numerous desirable features including compatibility with plastic microfluidic chips and compatibility with the electrical control system, and thus will fulfill the requirements of a fully automated cell analysis system.

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CMOS image sensor-based implantable glucose sensor using glucose-responsive fluorescent hydrogel

Cited by 38 publications

References 16 publications

A hydrogel-based glucose affinity microsensor

A hydrogel-based glucose affinity microsensor

Pixel pitch and particle energy influence on the dark current distribution of neutron irradiated CMOS image sensors

On-chip cell analysis platform: Implementation of contact fluorescence microscopy in microfluidic chips

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