Research in Cheng Laboratory
When a cell receives a signal from the environment or another cell, the internal machinery of the receiving cell is activated. However, we do not know exactly what happens then among all the elements (e.g. membrane reorganization, metabolic conversion) in the recipient cell. A detailed understanding of these events as they occur in live cells would pave the way for developing marker-based diagnosis strategies and designing disease-specific drugs. So far, most of our knowledge about cellular content comes from in vitro analysis of fixed cells or homogenates. For study in live cells, fluorescence microscopy is the tool of choice by monitoring labeled molecules in real time. However, the labels may muddy the physiology of small biomolecules such as cholesterol or the function of a biological structure such as the plasma membrane. Also, labeling can only be used to examine the behavior of a known molecular species. Label-free imaging using intrinsic signals offers an alternative to overcome these limitations. Among various label-free imaging modalities, Raman-scattering based vibrational imaging is most informative because each molecule has its fingerprint vibrational modes.
Molecular spectroscopy has been a powerful tool for quantitative analysis by measuring quantized electronic and vibrational transitions in molecules. Over the past, such measurements were restricted to molecules that are extracted from cells and tissues, or biopsies extracted from a human body. Such in vitro spectroscopy measurements lack the capabilities of tracing molecules in intact, live tissue environment. Spectroscopic imaging by measuring molecular fingerprint spectrum at each pixel, thus providing both molecular information and spatial resolution, would offer a new window for seeing a hidden world of biology. Five to ten years ago, spectroscopic imaging of living systems from single cell to human body was considered to be impossible. This “mission impossible” can be summarized as the following tasks: (1) Can we perform real time spectroscopic imaging of a live cell? (2) Can we derive meaningful information from the crowded fingerprint spectra recorded from an intact, extremely complicated biological complex? (3) Can we measure a spectrum in vivo from a target tissue that is a few cm underneath the skin?
My research group has been tackling the “mission impossible” very persistently. Our recent research endeavors have generated promising solutions allowing for spectroscopic imaging of life. We have two consecutive inventions that enabled fast spectroscopic imaging with a pixel dwell time of 10 microseconds, which is nearly 1 million times faster than conventional Raman spectroscopy. We have successfully bridged multivariate analysis tools with spectroscopic imaging. Such integration has allowed label-free imaging of biomolecules, such as cholesterol, in an intact tissue using their fingerprint bands. We have launched a novel imaging platform based on acoustic detection of chemical bond vibration. Continuous development of this method has allowed us to record a spectrum from a target tissue that is 3 cm deep below the surface.
1. Label-free spectroscopic imaging for biology and medicine.
2. Nanomedicine for nerve reapir and cancer chemotherapy