New Cheng study peers into chemical activity within living cells.
by A.J. Kleber
In a recent publication in Nature Methods, the prolific Professor Ji-Xin Cheng envisions the creation of “a high-resolution chemical cellular atlas” of living organisms, providing scientists and medical practitioners with an accessible map of the smallest building blocks that make up the complex edifice of life itself. The paper describes a novel methodology which represents a promising step in the direction of realizing that ambitious goal, with the support of a MIRA grant from the NIH’s National Institute of General Medical Sciences and a Small Business Innovation Research Award.
Fluorescence-detected mid-infrared photothermal microscopy (FILM) is a groundbreaking method which permits the study of key chemical processes in the body at an unprecedented level; that of individual organelles called lysosomes. These miniscule cellular components are found in nearly all animal cells, where they contribute to essential tasks such as digestion by breaking down various materials (like proteins and lipids). The metabolic changes within lysosomes have significant influence on an organism’s overall health, but there has been no viable method for measuring these chemical signatures in vivo … until now.
A product of converging expertise in chemistry, engineering, and biology, FILM combines Cheng’s pioneering mid-infrared photothermal (MIP) microscopy with fluorescent labeling techniques, a computational de-noising method called boxcar demodulation, and AI-assisted interpretation. The method’s unprecedented capacity to map the metabolic activity and composition of individual lysosomes in living cells and organisms is documented in the Nature Methods paper, which discusses some initial results, including observations on the heterogeneity of metabolic processes (lipolysis and proteolysis, the breakdown of lipids and proteins) across lysosomes within the same cell.
FILM demonstrates remarkable potential for mapping and assessing dynamic changes to intra-cellular chemical processes “within their native context,” promising fresh discoveries about the changes experienced by the body during aging or illness. The technology is licensed by Photothermal Spectroscopy Corp, a scientific instrument company co-founded by Cheng. It also represents an early collaborative effort by members of the recently-formed Chemical Imaging Initiative, which brings together Boston University faculty from diverse disciplines in pursuit of “decoding the chemistry of life.”
Professor Ji-Xin Cheng (ECE, BME, MSE, Physics, Chemistry) is the Theodore Moustakas Distinguished Professor in Photonics and Optoelectronics at Boston University. A Fellow of NAI, AIMBE and Optica, Cheng holds over 30 patents and is the recipient of numerous awards; most recently, the 2026 FACSS Charles Mann Award in Applied Raman Spectroscopy. His research is supported by millions of dollars in funding from government agencies and industry,