BioPhotonics Preview for January/February 2026

Raman Spectroscopy

Today, portable Raman spectrometers and microscopes offer high-resolution and real-time molecular analysis in both field and clinical settings. Breakthroughs in laser miniaturization, advances in optical design, the development of compact, high-sensitivity detectors, and the possibility to use dedicated optical probes have combined to enable the creation of smaller, more robust systems without compromising performance. In addition to diagnostics, the availability of these Raman instruments is enabling intraoperative tissue characterization and image-guided interventions. Moreover, their integration with wireless communication, cloud connectivity, and AI-powered data interpretation further enhances usability and remote diagnostics or decentralized workflows. Yet despite the vast potential of Raman spectroscopy and imaging in the medical sector, and even as progress continues in the technology space, the adoption of Raman methods in clinical environments faces several significant challenges. Independent of some technological limitations, translating Raman instruments from laboratory to clinical use demands rigorous standardization, validation, and regulatory approval, which can be time-consuming and costly. Also, the complexity of spectral data often necessitates the use of advanced algorithms and trained personnel for accurate analysis. And access to funds can also influence the evolution of the development and its final application. From within industry, companies are rising to the challenge to harness Raman’s capabilities while at the same time working to overcome obstacles to the full-scale clinical implementation of these techniques. The innovative approaches that these companies are deploying showcase a dynamic convergence of sophisticated instrumentation and high performance solutions.

Femtosecond Lasers and Fluorescence

Tryptophan is an essential amino acid which is, together with other amino acids, a constituent of most proteins. Tryptophan is fluorescent, and its fluorescence is the dominating part of protein fluorescence. Tryptophane fluorescence is dependent on biological parameters, such as protein constitution, protein folding, and presence of other amino acids in the closer molecular environment. This dependence makes tryptophan a potential fluorescence marker for molecular parameters in biological systems. In particular, this is the case when tryptophan fluorescence is detected by fluorescence lifetime imaging (FLIM). Problem is, the excitation wavelength of tryptophane is deep in the UV, and cannot be reached in a normal microscope. In this article we show how tryptophane lifetime images can be obtained by TCSPC FLIM in combination with two-photon excitation by a new green femtosecond laser.

Optical Filters

Filter orientation relative to the incoming beam dictates a filter’s performance. Understanding the angle of incidence (AOI) and cone half angle (CHA) requirements on the filters is critical for optimizing throughput and optical performance. The larger the AOI deviation from design, the greater the peak shift and overall transmission drop. Increasing the AOI blue shifts the transmission peak towards shorter wavelengths, whilst reducing the AOI red shifts the transmission peak towards longer wavelengths. The larger the CHA of the incoming light, the greater the loss in peak transmission and the peak broadening, which can result in unwanted wavelengths of light adjacent to the design wavelength passing through the filter. There are design techniques that can be implemented to decrease a filter’s sensitivity to the effects of AOI and CHA. This article discusses the importance of considering angular effects on filter performance in optical system design and offers mitigation strategies.

Superresolution Microscopy

Currently, there are two main approaches of superresolution microscopy that allow for imaging beyond the diffraction limit of light. One approach is spatial coordination via patterned illumination to differentially modulate the fluorescence emission of molecules within a diffraction-limited volume, which allows for separate detection of molecules within that volume. Popular techniques that fall under this approach are stimulated emission depletion (STED) and structural illumination microscopy (SIM). The second approach, and arguably the one best-suited for cell biology research questions, is single-molecule localization (SMLM). SMLM achieves the separation of molecules by stochastically exciting individual molecules within the diffraction-limited volume at different time points. Fluorescent labeling strategies for SMLM include the use of fluorescent proteins and organic dyes. Compared to STED and SIM, SMLM has the highest resolution. This article will focus primarily on the single-molecule localization microscopy method of superresolution.

Fairness in Image Classification

Recent advancements in deep learning have shown transformative potential in medical imaging, yet concerns about fairness persist due to performance disparities across demographic subgroups. Existing methods aim to address these biases by mitigating sensitive attributes in image data; however, these attributes often carry clinically relevant information, and their removal can compromise model performance - a highly undesirable outcome. To address this challenge, the team at Northwestern proposes Fair Re-fusion After Disentanglement (FairREAD), a novel, simple, and efficient framework that mitigates unfairness by re-integrating sensitive demographic attributes into fair image representations.