Technology
Our Technology: Multiplex SRS
The Cambridge Raman Imaging platform overcomes the limitations of traditional optical microscopy by offering label-free chemical imaging at ultra-high speeds. The core of our innovation lies in Multiplex Stimulated Raman Scattering (m-SRS) [1].
What is Multiplex SRS (m-SRS)?
Traditional SRS microscopy has a fundamental structural limitation: it can only acquire a single vibrational frequency (and thus, a single chemical signature) at a time. To map a tissue sample, researchers must capture multiple images in sequence while mechanically tuning the laser to different frequencies—a process that is both slow and inefficient.
Our Multiplex SRS approach solves this problem at the root:
- By combining a narrowband pump pulse with a broadband Stokes pulse, we illuminate the sample and stimulate the entire chemical spectrum simultaneously [1].
- Instead of acquiring sequential images, the system measures the complete chemical signature of every single pixel in just a few microseconds [2].
- This achieves an acquisition speed up to two orders of magnitude faster than standard single-frequency operation, eliminating artifacts, preventing sample photodamage, and opening the door to high-throughput spectral histopathology [3].
What makes it possible? The two technological pillars
While Multiplex SRS has long been a highly sought-after goal in optical imaging, it was historically hindered by the lack of adequate hardware. To turn this technology into a commercial reality, we designed and engineered the two key proprietary components of our system.
The Source
Synchronized, low-noise all-fiber laser
Generating a reliable m-SRS signal requires absolute temporal synchronization between the pump and Stokes laser pulses. We engineered a dual-wavelength all-fiber laser oscillator architecture that achieves this natively:
- Intrinsic synchronization: the laser houses two independent cavities (Erbium and Ytterbium). The Erbium cavity is passively mode-locked using state-of-the-art carbon nanotube-polymer composites [4]. By sharing a common arm, the two cavities self-synchronize passively via cross-phase modulation (XPM), ensuring exceptional long-term stability without complex active electronics [5].
- Spectral compression: to maximize power efficiency and narrow the bandwidth of the pump pulse precisely for optimal vibrational resolution, we utilize a highly efficient second-harmonic spectral compression technique in nonlinear crystals [8].
- Intrinsically low noise: traditional fiber architectures for single-frequency SRS rely on noisy nonlinear frequency conversion processes, forcing researchers to use complex balanced detection schemes to cancel out excess laser noise [6, 7]. Our custom design delivers high-power, ultra-clean pulses natively, maximizing imaging sensitivity.
The Detector
Multichannel lock-in amplifier (m-LIA)
Once the light transmits through the sample, a dispersive optical element angularly separates the wavelengths of the broadband Stokes pulse, projecting them onto a photodiode array. Reading out this massive stream of spectral data in parallel required an electronic solution that simply did not exist commercially. Our proprietary m-LIA is a custom-built innovation designed specifically for fast broadband SRS imaging [3]:
- Parallel readout: every single channel of the photodiode array is coupled directly to our high-frequency lock-in amplifier.
- Instantaneous processing: the m-LIA extracts and processes the SRS signals from all spectral channels at the exact same time. This allows the system to reconstruct high-resolution hyperspectral chemical maps at microsecond-per-pixel speeds [2, 3], making m-SRS a clinically viable technology ready for the future of diagnostics.
References
- Polli, D., Kumar, V., Valensise, C. M., Marangoni, M. & Cerullo, G. Broadband coherent Raman scattering microscopy. Laser Photon Rev. 12, 1800020 (2018).
- Liao, C. S. et al. Microsecond scale vibrational spectroscopic imaging by multiplex stimulated Raman scattering microscopy. Light Sci. Appl. 4, e265 (2015).
- De La Cadena A. et al., Broadband stimulated Raman imaging based on multi-channel lock-in detection for spectral histopathology. APL Photonics 7, 076104 (2022).
- Hasan, T. et al. Nanotube-polymer composites for ultrafast photonics. Adv. Mater. 21, 3874–3899 (2009).
- Zeng, J. et al. Passively synchronized dual-color mode-locked fiber lasers based on nonlinear amplifying loop mirrors. Opt. Lett. 44, 5061–5064 (2019).
- Nose, K. et al. Sensitivity enhancement of fiber-laser-based stimulated Raman scattering microscopy by collinear balanced detection technique. Opt. Express 20, 13958–13965 (2012).
- Crisafi, F., Kumar, V., Scopigno, T. et al. In-line balanced detection stimulated Raman scattering microscopy. Sci. Rep. 7, 10745 (2017).
- Marangoni, M. A. et al. Narrow-bandwidth picosecond pulses by spectral compression of femtosecond pulses in second-order nonlinear crystals. Opt. Express 15, 8884 (2007).
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Statements about future products represent management intentions, but are not to be considered commitments to any specific clinical or non-clinical capability or performance targets.