Ultrasmall compact CMOS imaging system for bioluminescence reporter-based live gene expression analysis Joshua Philippe Olorocisimo , a,b Jeric Briones , c,d Kiyotaka Sasagawa , a, * Makito Haruta , a Hironari Takehara , a Hiroyuki Tashiro , a,e Norihiro Ishida-Kitagawa, b Yasumasa Bessho, b and Jun Ohta a a Nara Institute of Science and Technology, Photonics Device Science Laboratory, Division of Materials Science, Graduate School of Science and Technology, Takayama, Ikoma, Nara, Japan b Nara Institute of Science and Technology, Gene Regulation Research Laboratory, Division of Biological Science, Graduate School of Science and Technology, Takayama, Ikoma, Nara, Japan c Nara Institute of Science and Technology, Mathematical Informatics Laboratory, Division of Information Science, Takayama, Ikoma, Nara, Japan d Advanced Telecommunications Research Institute International, Cognitive Mechanisms Laboratories, Kyoto, Japan e Kyushu University, Department of Health Sciences, Faculty of Medical Sciences, Higashi, Fukuoka, Japan Abstract Significance: Gene expression analysis is an important fundamental area of biomedical research. However, live gene expression imaging has proven challenging due to constraints in conven- tional optical devices and fluorescent reporters. Aim: Our aim is to develop smaller, more cost-effective, and versatile imaging capabilities com- pared with conventional devices. Bioluminescence reporter-based gene expression analysis was targeted due to its advantages over fluorescence-based imaging. Approach: We created a small compact imaging system using micro-CMOS image sensors (μCIS). The μCIS model had an improved pixel design and a patterned absorption filter array to detect the low light intensity of bioluminescence. Results: The device demonstrated lower dark current, lower temporal noise, and higher sensi- tivity compared with previous designs. The filter array enabled us to subtract dark current drift and attain a clearer light signal. These improvements allowed us to measure bioluminescence reporter-based gene expression in living mammalian cells. Conclusion: Using our μCIS system for bioluminescence imaging in the future, the device can be implanted in vivo for simultaneous gene expression imaging, behavioral analysis, and opto- genetic modulation. © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 International License. Distribution or reproduction of this work in whole or in part requires full attribution of the original pub- lication, including its DOI. [DOI: 10.1117/1.JBO.26.11.116002] Keywords: biophotonics; micro-CMOS; image sensors; bioluminescence; luciferase; gene expression. Paper 210223R received Jul. 15, 2021; accepted for publication Oct. 18, 2021; published online Nov. 3, 2021. *Address all correspondence to Kiyotaka Sasagawa, sasagawa@ms.naist.jp Journal of Biomedical Optics 116002-1 November 2021 • Vol. 26(11) Downloaded From: https://www.spiedigitallibrary.org/journals/Journal-of-Biomedical-Optics on 28 Nov 2023 Terms of Use: https://www.spiedigitallibrary.org/terms-of-use