Researchers at Boston University have created Chem-SIM, an imaging technique that pairs structured illumination microscopy with mid-infrared photothermal fluorescence detection. Reporting in Nature Communications, the team demonstrated high-throughput super-resolution chemical mapping across microorganisms and mammalian cells while maintaining sample viability.
Standard structured illumination microscopy resolves fine subcellular architecture but provides little information about underlying chemical composition. Chem-SIM addresses this limit by modulating fluorescence through mid-infrared photothermal excitation. The system uses Poisson maximum-likelihood demodulation and spectral normalization across wavenumbers to detect subtle infrared-induced fluorescence changes under low photon counts, translating those variations into vibrational chemical fingerprints.
Aqueous imaging environments typically produce background interference from water. Chem-SIM applies photothermal gating to reject water background signals in aqueous samples, while its infrared pump keeps specimens at near-physiological temperatures to preserve cellular activity. The camera-based architecture preserves vibrational fingerprints while matching the lateral resolution of standard structured illumination microscopy.
The authors validated the platform across several biological test cases. The system mapped chemical content to differentiate stationary-phase bacteria from log-phase bacteria, tracked the incorporation of deuterated fatty acids in ovarian cancer cells, and recorded lipid-droplet dynamics inside living cells.
The study was authored by Dashan Dong, Danchen Jia, Jianpeng Ao, George Abu-Aqil, Meng Zhang, Qing Xia, Xinyan Teng, Biwen Gao, and Ji-Xin Cheng from Boston University's electrical and computer engineering, chemistry, and biomedical engineering departments, along with the Boston University Photonics Center. The work received support from the Chan Zuckerberg Initiative DAF and National Institutes of Health grants R35GM136223, R01AI141439, and R33CA287046. Cheng disclosed a financial interest in Photothermal Spectroscopy Corp, which did not fund the project.
