Vision of our research:

Optical spectroscopy has been a powerful tool for quantitative molecular analysis by measuring quantized electronic and vibrational transitions in molecules. In the past, such measurements were restricted to molecules that are extracted from cells and tissues, or biopsies extracted from a human body. Such point spectroscopy measurements are unable to trace molecules in an intact, live tissue environment. Spectroscopic imaging by measuring the molecular fingerprint spectrum at each pixel, thus providing both molecular information and spatial resolution, would offer a new window for seeing a hidden biological world. Five to ten years ago, spectroscopic imaging of living systems from a single cell to the human body was considered to be impossible. This “mission impossible” can be summarized by the following tasks: (1) Can we perform real time spectroscopic imaging of a live cell? The convention is that it takes a few seconds to record a point spectrum. For real time spectroscopic imaging, one needs to increase the speed by 1000,000 times to a few microseconds per pixel. (2) Can we derive meaningful information from the crowded fingerprint spectra recorded from an extremely intricate biological complex? The conventional thinking is that one should purify the molecule from the tissue before an assay by LC-MS or HPLC. (3) Can we measure a spectrum in vivo from a target tissue that is a few centimeters underneath the skin? Conventionally, tissue biopsies are needed for optical spectroscopy measurements because photons have very limited penetration depth into a tissue. My research lab has been addressing this "mission impossible" very persistently.

   Towards the first “impossible task”, 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. The ideas for these two patents, which have attracted interest from both Olympus and Leica towards commercialization, were based on the cochlea model of BME305 “biomedical instrumentation” that I have been teaching over the past 5 years. Towards the second task, we have teamed with analytical chemists at Purdue and 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. Towards the third task, we have launched a novel imaging platform based on acoustic detection of chemical bond vibration (PCT filed 2012). Continuous development of this method has allowed us to record a spectrum from a target tissue that is 3 cm below the surface, a task that was considered impossible when experts commented on our first photoacoustic paper published in Phys Rev Lett in 2011. The potential of this development is transformative, as it would allow diagnosis of vulnerable plaques in atherosclerosis, so that a stent can be inserted properly to save patient’s life. This development would also allow early detection of malignancy, such as pancreatic cancer, so that surgery can be performed before the tumor spreads to other organs.

   We have continued to employ these advanced instruments to tackle challenging questions in medicine. The Weldon School offered an unparalleled environment for me to cross the boundaries of disciplines and merge expertise in physics, chemistry, biology and engineering. By leading a highly interdisciplinary team spanning Purdue University, IU School of Medicine, MD Anderson Cancer Center and Dana-Farber Cancer Institute, we recently made a breakthrough in the study of lipid metabolism in aggressive forms of human cancer. In short, we discovered an aberrant cholesterol metabolism in aggressive prostate, pancreatic, breast, and brain cancer, and the list continues to grow. This discovery opened two transformative opportunities: early diagnosis of aggressive tumors using the elevated cholesterol metabolites as a spectroscopic imaging marker, and suppression of cancer aggressiveness by targeting the altered cholesterol metabolism. These projects are currently strongly supported by the Purdue Center for Cancer Research.

 

Current projects are:

 

1 Novel platforms for label-free spectroscopic imaging of living cells.   

Most recent publications 

135. Mikhail Slipchenko, Robert A. Oglesbee, Delong Zhang, Wei Wu, Ji-Xin Cheng*, “Heterodyne Detected Nonlinear Optical Microscopy in a Lock-in Free Manner”. Journal of Biophotonics, Oct 2012, 5:801-807.

111. Yookyung Jung,  Mikhail N. Slipchenko, Chang Hua Liu, Zhaohui Zhong, Chen Yang, Ji-Xin Cheng, "Fast detection of the metallic state of individual single-walled carbon nanotubes using a transient-absorption optical microscope", Phys Rev Lett, 2010, 105:217401.

104. Tong, L.; Cobley, C. M.; Chen, J.; Xia, Y. and Cheng, J.-X., Bright three-photon luminescence from Au-Ag alloyed nanostructures for bio-imaging with negligible phototoxicity, Angewandte Chemie International Edition 2010, 49: 3485-88. Inside Cover, Supporting information

103. Ning Bao, Thuc T. Le, Ji-Xin Cheng and Chang Lu, Microfluidic electroporation of tumor and blood cells: observation of nucleus expansion and implications on selective analysis and purging of circulating tumor cells, Integrative Biology, 2010, 2,113-120.

 

2 Seeing deep tissue by listening to molecular vibration

Most recent publications

Pu Wang#, Han-Wei Wang#, Michael Sturek, Ji-Xin Cheng*, # equal contribution, “Bond-selective imaging of deep tissue through the optical window between 1.6 and 1.85 micron” Journal of Biophotonics, 2011 January, 5: 25-32.

Han-Wei Wang Ning Chai, Pu Wang, Song Hu, Wei Dou, David Umulis, Lihong V. Wang, Michael Sturek, Robert Lucht, Ji-Xin Cheng*, “Label-free bond-selective imaging by listening to vibrationally excited molecules”, Phys Rev Lett, 2011, 106: 238106.  Supplemental Information, highlighted in Science and  “NIH Research Matters”.

 

3 Chasing the altered metabolism

Most recent publications 

133.1Shuhua Yue, Juan Cárdenas-Mora, Lesley Chaboub, Sophie, Lelievre*, Ji-Xin Cheng*, "Label-free Analysis of Breast Tissue Polarity by Raman Imaging of Lipid Phase", Biophysical Journal, March 2012, 102 (5), 1215-1223

134. Wei Dou, Delong Zhang, Yookyung Jung, Ji-xin Cheng* and David M Umulis*, "Label-Free Imaging of Lipid-Droplet Intracellular Motion in Early Drosophila Embryos Using Femtosecond Stimulated Raman Loss Microscopy", Biophysical Journal, April 2012, 102: 1666-75.

110. Thuc Le, Shuhua Yue, Ji-Xin Cheng, "Shedding new light on lipid biology by CARS microscopy", Journal of Lipid Research (review), 2010, 51:3091.

109. Kelvin Yen, Thuc T Le, Ankita Bansal, Sri Devi Narasimhan, Ji-Xin Cheng, and Heidi Tissenbaum, “A Comparative Study of Fat Storage Quantitation in Nematode Caenorhabditis elegans Using Label and Label-Free Methods”, PLoS ONE, 2010, 5: e12810.

105. Bonggi Lee, Angela M. Fast, Jiabin Zhu, Ji-Xin Cheng, Kimberly K. Buhman, Intestine specific expression of acyl coA: diacylglycerol acyltransferase 1 (DGAT1) reverses resistance to diet-induced hepatic steatosis and obesity in Dgat1-/- mice, Journal of Lipid Research, 2010, 51: 1770-80.

100. Thuc T. Le, Holli M. Duren, Mikhail N. Slipchenko, Chang-Deng Hu, Ji-Xin Cheng, “Label-free Quantitative Analysis of Lipid Metabolism in Living Caenorhabditis elegans”, Journal of Lipid Research, 2010, 51: 672. published online.

 

4 Nanomedicine for cancer chemotherapy and neuroprotection. 

     

Most recent publications

102. Sungwon Kim, Yunzhou Shi, Ji Young Kim, Kinam Park, Ji-Xin Cheng, “Overcoming the Barriers in Micellar Drug Delivery: Loading Efficiency, in vivo Stability, and Micelle-Cell Interaction”, Expert Opinion on Drug Delivery, 2010, 7: 49-62.

101. L. Li, I. Geisler, J. Chmielewski, J. X. Cheng, “Cationic amphiphilic polyproline helix P11LRR targets intracellular mitochondria”, J. Control. Release, 2010 142: 259-266.

98. Yunzhou Shi, Sungwon Kim, Terry B. Huff, Richard Borgens, Kinam Park, Riyi Shi, Ji-Xin Cheng, “Bock copolymer micelles effectively repair traumatically injured spinal cord white matter”, Nature Nanotechnology, 2010, 5: 80-87. supporting information.