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

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.

Broadband Coherent Raman Scattering Microscopy

“…have incorporated an intra‐cavity AOTF‐based picosecond mode‐locked laser in an hyperspectral CARS setup to achieve fast spectral scanning with speed approaching 20 ms per wavelength change including cavity resynchronization time with a spectral resolution of ≈4 cm −1 . Likewise, Mars et al . have used a picosecond mode‐locked 80 MHz Ti:sapphire laser equipped with an AOTF inside the laser cavity to directly obtain tunable Stokes pulses which were further intensity modulated at 20 MHz by an EOM placed outside the cavity, while a similar synchronized picosecond Ti:sapphire laser was used as a pump source.…”

Современные Концепции Изучения Процессов Коррозионной Деградации Материалов И Покрытий: Теория, Практика, Методология Исследований

“…Широкая полоса при 1660 см -1 связана с валентным колебанием связи ν(C=O) в карбоксильной группе [784]. Два пика при 2840 см -1 и 2890 см -1 обусловлены симметричным и асимметричным валентными колебаниями ν(CH 2 ) [785]. Полоса при 890 см -1 относится к маятниковому колебанию метильной группы (CH 3 ) [784].…”

Four-Channel Differential Lock-in Amplifiers With Autobalancing Network for Stimulated Raman Spectroscopy

“…The drawbacks of this solution are the fixed by design SRS modulation frequency, the request for a careful calibration of the filters and the sub-optimal noise rejection operated by a peak detector with respect to the lock-in technique. A different architecture for a parallel acquisition is reported in [24] [25], where a 10x10 pixels CMOS lock-in camera with on-chip photodetectors is proposed. Although the frequency scanning is sequential, the frame rate is increased by the acquisition of several pixels in parallel in the space domain.…”