Microscopy has always been a cornerstone of cell biology. As scientists dig deeper into the molecular workings of life, there’s a growing need for imaging technologies that can go beyond surface-level views — tools that are fast, precise, and gentle enough to work with living cells. That’s where Raman-based techniques come in.
Raman Spectroscopy: A window into cell chemistry
Raman spectroscopy allows researchers to explore the cells’ molecular makeup and their surroundings without the need for dyes or labels. It can pick up chemical details in the cell culture medium, but also, more importantly, within the cells themselves, revealing insights into lipids, proteins, or even DNA and RNA.
The challenge? Spontaneous Raman signals are naturally weak. This means that every photon counts. Instruments need to be engineered with care to minimize losses and keep detector noise tightly controlled. In this field, good biology depends on great optical systems to ensure meaningful data capture.
SRS and CARS: Speeding things up with nonlinear microscopy
To overcome the limitations of spontaneous Raman, nonlinear optical microscopy (NLOM) techniques like Stimulated Raman Scattering (SRS) and Coherent Anti-Stokes Raman Scattering (CARS) have become increasingly popular. By enhancing the Raman signal several orders of magnitude, they make it possible to image living cells and tissues quickly, and still get rich, chemically specific information, without introducing any fluorescent labels.
Building systems like these is challenging, as they demand precise optical setups, ultrafast lasers, and signal optimization at every stage of the system. Their implementation is a multi-disciplinary effort, combining optics, electronics, and systems engineering to meet the stringent requirements of biological imaging.
These techniques are particularly relevant for studying dynamic cellular processes such as metabolism, cell differentiation, and disease progression. Being able to monitor and understand molecular changes in real time opens new doors for both research and medical diagnostics.
Putting it to the test: a BSL-1 lab for live-cell validation
To support the refinement and application of such technologies, a Biosafety Level 1 (BSL-1) laboratory was established at Lambda-X Verhaert High-Tech. The lab provides a controlled environment to test and demonstrate microscopy systems in real biological conditions. This hands-on validation is particularly valuable for evaluating how advanced Raman-based imaging performs in live-cell scenarios, helping translate optical performance into biological relevance.
From research tools to process monitoring
While these technologies were first developed for fundamental research, their applications extend into areas like cell therapy, where understanding and controlling cell behavior is crucial. As such therapies move closer to clinical and industrial deployment, analytical tools based on nonlinear Raman microscopy offer potential for process monitoring, supporting quality control and decision-making during cell culture and expansion.
By combining advanced optical engineering with live-cell validation in the lab, nonlinear microscopy is shifting from a powerful research technique to a real enabler in next-generation cell research and therapeutic manufacturing.
Exploring advanced optical solutions for your imaging needs? Let’s talk how to collaborate on developing systems that align cutting-edge photonics with real biological applications.