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Sensors 2017, 17(11), 2581; https://doi.org/10.3390/s17112581

Label-Free Biomedical Imaging Using High-Speed Lock-In Pixel Sensor for Stimulated Raman Scattering

1
Research Institute of Electronics, Shizuoka University, 3-5-1 Johoku, Nakaku, Hamamatsu, Shizuoka 432-8011, Japan
2
Mitsubishi Electric Corporation Nagoya Works, FA System Manufacturing Department, Manufacturing Engineering Section, 1-14, Yada-minami 5-chome, Higashi-ku, Nagoya, Aichi 461-8670, Japan
3
Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan
4
Graduate School of Information Science and Technology, Hokkaido University, Kita 14, Nishi 9, Kita-ku, Sapporo 060-0814, Japan
*
Author to whom correspondence should be addressed.
Received: 1 August 2017 / Revised: 30 October 2017 / Accepted: 7 November 2017 / Published: 9 November 2017
(This article belongs to the Section Physical Sensors)
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Abstract

Raman imaging eliminates the need for staining procedures, providing label-free imaging to study biological samples. Recent developments in stimulated Raman scattering (SRS) have achieved fast acquisition speed and hyperspectral imaging. However, there has been a problem of lack of detectors suitable for MHz modulation rate parallel detection, detecting multiple small SRS signals while eliminating extremely strong offset due to direct laser light. In this paper, we present a complementary metal-oxide semiconductor (CMOS) image sensor using high-speed lock-in pixels for stimulated Raman scattering that is capable of obtaining the difference of Stokes-on and Stokes-off signal at modulation frequency of 20 MHz in the pixel before reading out. The generated small SRS signal is extracted and amplified in a pixel using a high-speed and large area lateral electric field charge modulator (LEFM) employing two-step ion implantation and an in-pixel pair of low-pass filter, a sample and hold circuit and a switched capacitor integrator using a fully differential amplifier. A prototype chip is fabricated using 0.11 μm CMOS image sensor technology process. SRS spectra and images of stearic acid and 3T3-L1 samples are successfully obtained. The outcomes suggest that hyperspectral and multi-focus SRS imaging at video rate is viable after slight modifications to the pixel architecture and the acquisition system. View Full-Text
Keywords: CMOS image sensor; stimulated Raman scattering; lock-in pixel; Raman shift; low-noise; high-speed modulation CMOS image sensor; stimulated Raman scattering; lock-in pixel; Raman shift; low-noise; high-speed modulation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Mars, K.; Lioe, D.X.; Kawahito, S.; Yasutomi, K.; Kagawa, K.; Yamada, T.; Hashimoto, M. Label-Free Biomedical Imaging Using High-Speed Lock-In Pixel Sensor for Stimulated Raman Scattering. Sensors 2017, 17, 2581.

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