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

Abstract

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.

Ultrasmall compact CMOS imaging system for bioluminescence reporter-based live gene expression analysis

“…Two kinds of CIS chips were designed and manufactured: the 3T-APS using 0.35-m standard CMOS process and the 4T-APS using 0.18-m CIS process. These chips were then assembled to create the previous device model 5 , 6 , 8 – 12 and the new device model featured in this study. The devices were modified and tested in this study to detect bioluminescence signal and image gene expression.…”

“…We have previously reported the use of these ultrasmall for fluorescence imaging applications (e.g., ELISA, imaging, and FRET). 8 – 10 However, fluorescence imaging requires outside excitation light, which causes high background noise. An effective excitation cut-off filter needs to be designed, which is difficult for small and lensless imaging devices.…”

Thin and Scalable Hybrid Emission Filter via Plasma Etching for Low-Invasive Fluorescence Detection

“…According to reports, this hybrid filter exhibited a higher rejection level than a single filter [ 22 ]. Moreover, by reducing the autofluorescence of the absorption filter, the hybrid filter increased the excitation rejection performance of a lensless device, making it comparable to a typical lens-based fluorescent microscope [ 23 , 24 , 25 , 26 , 27 , 28 ]. However, using this hybrid filter for microimaging devices requires thickness reduction to an acceptable invasiveness level.…”

Image sensor with hybrid emission filter for in vivo fluorescent imaging

“…Important elements in fluorescent observations are filters that reject excitation light and transmit only fluorescence, but sufficient performance cannot be achieved in a lensless system even when using high‐performance interference filters employed in fluorescent microscopes. In this context, we recently developed hybrid filters that offer high performance of excitation light rejection in lensless systems 13–16 . This paper explains about providing the implantable image sensor with a hybrid bandpass filter.…”

“…In this context, we recently developed hybrid filters that offer high performance of excitation light rejection in lensless systems. [13][14][15][16] This paper explains about providing the implantable image sensor with a hybrid bandpass filter.…”