Intravital fluorescence imaging of mouse brain using implantable semiconductor devices and epi-illumination of biological tissue

Takehara, Hiroaki; Ohta, Yasumi; Motoyama, Mayumi; Haruta, Makito; Nagasaki, Mizuki; Takehara, Hironari; Noda, Toshihiko; Sasagawa, Kiyotaka; Tokuda, Takashi

doi:10.1364/boe.6.001553

Cited by 30 publications

(28 citation statements)

References 45 publications

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“…FRET based fluorescent probes demonstrate large stokes shift due to intramolecular energy transfer, and thus, were selected for use in the on-chip fluorescence detection system with dye-based absorption filter in the present study. 23 Cellular response to extracellular agents was induced by delivering EGF. As presented in Fig.…”

Section: On-chip Fluorescence Imaging and Detection Of Cellular Activitymentioning

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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Section: On-chip Fluorescence Imaging and Detection Of Cellular Activitymentioning

confidence: 99%

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

et al. 2017

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“…(4,7,9) Previous research has already shown that the fabrication of small yet high-resolution image sensors is possible for various purposes, such as observing the brain activity of rodents, (15) illuminating and detecting light in deep biological tissues for optical therapy and diagnosis, (16) and optogenetics. (17) Moreover, it is possible to insert a small image sensor in an incubator to observe cultured cells for a long period of time, (3,6,8,11,12) and also possible to develop a similar image sensor for long-term Förster resonance energy transfer (FRET) observation in a small animal.…”

Section: Introductionmentioning

confidence: 99%

Lens-free Dual-color Fluorescent CMOS Image Sensor for F?rster Resonance Energy Transfer Imaging

Hee¹,

Sasagawa²,

Kameyama³

et al. 2019

Sensors and Materials

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In this study, a lens-free dual-color bio-imaging system is developed. This system utilizes a small CMOS image sensor chip as the imager. By coupling alternate lines of blue and yellowgreen filters coated on photodiodes, we can simultaneously detect cyan and yellow fluorescent lights using the device. By equipping the device with a hybrid filter made of a bandpass interference filter, a fiber optic plate (FOP), and a pale-yellow absorption filter, we can achieve an excitation light extinction ratio of approximately −57 dB. By using fluorescent beads of two different colors, we can confirm the operation of the image sensor. Individual images from the cyan and yellow channels can be obtained after data processing, and subsequently the yellow-tocyan image ratio can also be determined. The results show that our device can be used to study Förster resonance energy transfer (FRET) and can thus be applied to investigate the progression of diseases such as cancer.

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“…9 Several authors have developed neural devices with CMOS image sensors for fluorescence imaging or intrinsic signal imaging. 12,13 Kobayashi et al 9 reported an implantable device with a CMOS image sensor and dual light emitting diodes (LEDs) for photostimulation and fluorescence imaging. The authors reported the use of blue LEDs for photostimulation, green LEDs for fluorescence excitation, and an absorption filter (long-pass liquid photoresist filter: >600 nm) superimposed on the CMOS image sensor, to pass the fluorescence and intercept the stimulation and excitation light.…”

Section: Introductionmentioning

confidence: 99%

High-selectivity neural probe based on a Fabry–Perot optical filter and a CMOS silicon photodiodes array at visible wavelengths

et al. 2018

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This paper presents a silicon neural probe with a high-selectivity optical readout function and light emitting diodes for neurons photostimulation and fluorophore excitation. A high-selectivity Fabry-Perot optical filter on the top of a CMOS silicon photodiodes array can read the emitted fluorescence, which indicates the neurons physiological state. The design, fabrication, and characterization of the optical filter are presented. The SiO 2 ∕TiO 2 based optical filter thin films were deposited by RF sputtering. The performance of the optical filter deposited on the top of the silicon photodiodes array, implemented in the neural probe, was tested through in-vitro fluorescence measurements. The transmittance peak of the fabricated optical filter is 81.8% at 561 nm, with a full width at half maximum of 28 nm. The peak responsivity of the CMOS silicon photodiode with the optical filter deposited on its top is 273.6 mA∕W at 578 nm. The in-vitro fluorescence measurements results show a CMOS photodiode current proportional to the fluorophore concentration with a good linearity (R 2 ¼ 0.9361). The results validate the use of the neural probe with the high-selectivity optical readout function to determine the presence of different fluorophore concentrations. The development of the device in a conventional CMOS process allows on-chip electronics readout.

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Intravital fluorescence imaging of mouse brain using implantable semiconductor devices and epi-illumination of biological tissue

Cited by 30 publications

References 45 publications

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

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

Lens-free Dual-color Fluorescent CMOS Image Sensor for F?rster Resonance Energy Transfer Imaging

High-selectivity neural probe based on a Fabry–Perot optical filter and a CMOS silicon photodiodes array at visible wavelengths

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