BE Seminar – Rohit Bhargava, “Chemical imaging: engineering a bridge between morphology and molecular composition in biomedical sciences”

Biomedical imaging has typically focused on morphological or architectural imaging, at times using special dyes or agents to enhance contrast by targeting specific chemicals. A new approach to record both morphology and inherent chemical composition is emerging by recording vibrational absorption and scattering from biomedical materials. Codified as Chemical Imaging, this approach is a convenient route to a quantitative, sensitive and reproducible fingerprint of composition at every pixel in a microscopy image. Combined with artificial intelligence (AI) workflows, several translational problems can be addressed. Here, we will present three examples of how this technology is developed and used. First, we seek to translate the ease of use and confidence in results in chemical imaging to the complex processes used to diagnose cancer with desirable, but yet unattainable, precision. By developing infrared (IR) spectroscopic imaging via a compact new microscope, our goal is to enable universal cancer diagnoses by using the native chemical composition of tissue. Our approach relies on theoretical models of light propagation and sample interactions in an IR microscope that we devised to formulate design rules for optimal image quality. Using quantum cascade lasers as spectrally tunable sources, we report here new optics to realize theoretically limited microscopy performance. This system simultaneously allows ~micron-scale image quality and better spectral quality than common bulk spectrometers. Integrating novel AI workflows, this system is being translated to clinical sites for real-time cancer pathology. Second, we use similar ideas to examine composition of growing cells and tissues to drive controlled organoid growth. Third, new modeling and instrument development are now allowing us to explore the limits of chemical imaging. We describe the development and performance of a nanoscale IR imaging instrument that promises practical imaging speeds and high spectral quality at tens of nm resolution, ultimately aiming to record every molecule in a cell.

Rohit Bhargava is a Professor of Bioengineering, Grainger Distinguished Chair in Engineering and the Phillip and Ann Sharp Director of the Cancer Center at Illinois at the University of Illinois Urbana-Champaign. His contributions to theory, instrumentation and applications have helped develop the field of infrared chemical imaging since its inception. Current research focuses on the applications of chemical imaging to histopathology and to quantitative cell biology. Using a combination of advanced manufacturing techniques, novel imaging and artificial intelligence, another major direction in his laboratories is to advance production of designer tumor models. His research is supported by the NIH, NSF, DoD, ARPA-H, Chan-Zuckerburg Biohub and Mayo Clinic. Rohit has also served to connect the research community in new directions. He was the first external hire in the UIUC Bioengineering department, developed the NIH T32-supported Microenvironment Training Program, and founded the Cancer Center at Illinois – a basic cancer center at the convergence of engineering and oncology. He is a proponent of the emerging field of Cancer Engineering. He holds a B.Tech. degree from the Indian Institute of Technology, New Delhi as well as a doctoral degree from Case Western Reserve University, Cleveland and conducted postdoctoral research at the National Institutes of Health, Bethesda, prior to joining the faculty at Illinois.