An Interview with ACS Award in Spectrochemical Analysis Recipient Ji-Xin Cheng

Per the American Chemical Society Division of Analytical Chemistry website (1), their annual Award in Spectrochemical Analysis honors those advancing the fields of spectrochemical analysis and optical spectrometry. This year’s recipient is Ji-Xin Cheng, Moustakas Chair Professor of Photonics and Optoelectornics at Boston University. Cheng will be receiving his award at this year’s SciX conference, to be held from October 20 through October 25, in Raleigh, North Carolina. As part of an ongoing series of this year’s SciX conference honorees, Ji-Xin spoke to Spectroscopy Magazine about his career and his life.

Can you discuss the most significant historical milestones in the development of infrared (IR) microspectroscopy from its early inception with the first commercial infrared microspectrometer in 1953 to the introduction of modern techniques like mid-infrared photothermal (MIP) microscopy?
There are quite a few. Along the direction of chemical imaging, the coupling of Fourier transform-infrared (FT-IR) spectrometer with a focal plane array detector (2) enabled FT-IR imaging of biological tissues and has led IR spectroscopy based chemical histology now pursued by multiple groups. Around 2000, two technologies were invented to push the IR imaging resolution to nanoscale. One is based on detection of IR scattering from an atomic force microscopy (AFM) tip, the other is based on AFM tip detection of infrared absorption induced sample expansion. These technologies are now commercially available. The concept of optical photothermal imaging based on change of refract index was reported in Le Journal de Physique Colloquesin 1983 (3). Yet, it waited over 30 years for optical photothermal infrared imaging become a practical tool for super-resolution infrared spectroscopic imaging of function materials and live cells. After 5 years of persistent effort, my group published a high-performance mid-infrared photothermal (MIP) microscope in Science Advances in 2016 (4), achieving 600 nm spatial resolution and a 10 micromolar limit of detection for the carbonyl (C=O) bond. This paper was quickly converted into a product “mIRage” by Anasys Instruments Inc. in 2017. In 2018, Photothermal Spectroscopy Corporation was formed to further develop this technology. Since then, mIRage has been delivered to over 100 research labs in over 15 countries. Very broad applications are reported.

How do the absorption cross sections of IR spectroscopy and stimulated Raman scattering (SRS) influence their respective sensitivities and applications in biological imaging?
This is an excellent question. The cross section of infrared absorption ranges from 10-17 to 10-22 cm2/molecule. In comparison, the cross section of spontaneous Raman scattering is on the order of 10-30 cm2/molecule/sr. The much larger cross section of infrared absorption promises high-sensitivity vibrational imaging. Yet, the long wavelength of mid-infrared light blues the spatial resolution to a few micrometers. The invention of MIP or OPTIR microscopy, breaks the infrared light diffraction limit through a pump-probe approach.

Stimulated Raman scattering (SRS), which involved a pump beam and a Stokes beam, can be recast as a two-photon vibrational absorption process. The apparent cross section of SRS is on the order of 10-22 cm2/molecule, not far from mid-infrared absorption. My group recently reported a stimulated Raman photothermal (SRP) microscope (5) for photothermal imaging of Raman-active modes.

What were the primary challenges with traditional FT-IR microscopes in biological applications, and how does MIP microscopy address these issues?
FT-IR microscopes face three challenges. First, the resolution is limited to infrared light diffraction limit. Second, it is not applicable to imaging live cells in liquid medium due to strong water absorption. Third, the FT-IR spectral profile can be influenced by sample scattering of infrared light. MIP microscopy, based on infrared light pump, and visible light probe, addressed all these three issues. MIP’s resolution reaches visible diffraction limit which is around 300 nm. MIP is applicable to live cell and in vivo imaging as the visible light can transmit through a cell culture or reflected from a thick tissue. MIP measures the infrared absorption using a fixed visible wavelength; thus, the spectral profile is not dependent on the particle size.

Could you elaborate on the impact of quantum cascade laser (QCL) technology on IR spectroscopy, particularly regarding spatial resolution and its limitations?
The QCL technology much increased the IR imaging speed, since it allowed IR spectroscopic imaging at discrete wavelengths, as demonstrated by the Bhargava group at University of Illinois Urbana-Champaign. It does not help the resolution too much, as the resolution is proportional to the wavelength. QCL as a reliable excitation source greatly helped the development of MIP microscopy.

In what ways has the development of AFM-IR and its subsequent limitations influenced the direction of research in super-resolution IR imaging technologies?
AFM-IR has enabled IR image at nanometer scale. Yet it is only applicable to flat specimens in dried condition, not applicable to liquid specimens, nor live systems. Notably, AFM-IR greatly helped the commercialization of MIP technology. Anasys Instruments Inc, which commercialized MIP into mIRage, was an industrial leader of AFM-IR before the company sold the technique to Bruker.

What inspired your interest in engineering in general?
My genuine curiosity of seeing the unseen or doing new things by making new tools. When I was a child, I was able to show how air pressure can push a tea-boiled egg into a bottle after lighting a match inside the bottle. I repeated this performance and amazed other kids during the Chinese Spring Festival. I was proud of that as a kid of around eight years old.

I grew up in the countryside of China. In my childhood during 1970s, my farmer parents did not even know what a toy is. In my memory, I made a car composed of a body and, two sticks, and four wheels with black soil. I managed to bake the car in the old-days kitchen using wood as fire. Amazingly, the car was able to run on the ground! I never dreamed that 30 years later, I spear-headed the development of the coherent anti-Stokes Raman scattering(CARS) microscope in Sunney Xie’s lab at Harvard University.

Did you always want to be a professor?
By the time I came to Harvard as a postdoc, my only intention was that I wanted to have a chance to taste what the best science is. I never planned to come to United States to be a professor. When the hard work was done and the CARS papers were published, it became natural to search for a faculty position. I submitted 15 applications and was granted 11 onsite interviews. In the end, I joined Purdue University as an assistant professor of biomedical engineering.

Do you consider yourself to be an engineer who is also a professor, or a professor who is also an engineer?
I would consider myself a professor since the hard work was done by students and postdocs. I spent most time writing proposals, mentoring next generation scientists, and brainstorming crazy new ideas together with my team.

Per your group website (6), you carried out your PhD at the University of Science and Technology of China (USTC), but you also worked as a research assistant at Universite Paris-sud (France) on vibrational spectroscopy and the Hong Kong University of Science and Technology (HKUST) on quantum dynamics theory. What was the experience of travel like for you, and what lessons did you learn that still influence you today?
I learned a lot from my advisors and the research teams at USTC, Paris, Hong Kong, and Harvard. The travels broadened my eyes and helped me clarify what I want—that is, to pursue the very best science. During my short postdoc at HKUST, my advisor sent me to the Xie lab at Harvard for a three-month visit. During that visit, I helped the Xie group publish its first paper from Harvard and that got me a postdoc position.

Studying and working in different places helped me build the confidence of doing new research, entering new fields, and grasp new concepts quickly. This substantially shaped my research style, that is, no fear of doing new things that I have no background.

You are credited as an author or coauthor on over 320+ peer-reviewed articles with an h-index of 101. Briefly speak about your first, as well as other memorable ones you’re associated with.
My first paper in 1995 was based on my undergraduate research at USTC. Nearly all my memorable papers were not produced by design, but by paying attention to unexpected observations. For example, we reported an unexpected finding of faster photodamage in CARS microscopy under the Raman resonance condition in the Journal of the Optical Society of America B: Optical Physics in 2007 (7). This observation trigged us to pursue a photoacoustic approach for bond-selective imaging. More recently, our development of a phototherapy for MRSA treatment (8) was based on an unexpected observation of rapid photobeaching of chromophores in S. aureus in a pump-probe imaging experiment.

What are some of your hobbies? What do you like doing when you’re not in the classroom or the laboratory?
On regular basis, I swim with my two sons on Tuesday evening, go to the gym for a private lesson on Thursday after work, and play tennis with my research team members on Saturday afternoon. I wish to have more time reading broadly.

What do you think (or hope) that your students and colleagues would say about you?
Haha! I wish that I can be counted as a visionary scientist, an innovator, a dedicated educator, and a human being with a kind mind.

What does receiving the ACS Analytical Division Award in Spectrochemical Analysis mean to you?
As a spectroscopist, I am very honored to receive the ACS Analytical Division Award in Spectrochemical Analysis.

References

1. ACS Division of Analytical Chemistry website. https://acsanalytical.org/awards-resources/national-acs-awards/spectrochemical-analysis-2/ (accessed 2024-07-15)

2. Lewis, E. N.; Treado, P. J.; Reeder, R. C.; Story, G. M.; Dowrey, A. E.; Marcott, C.; Levin, I. W. Fourier Transform Spectroscopic Imaging Using an Infrared Focal-Plane Array Detector. Anal. Chem. 1995, 67(19), 3377–3381. DOI: 10.1021/ac00115a003

3. Fournier, D.; Lepoutre, F. Tomographic Approach for Photothermal Imaging Uusing the Mirage Effect. Le Journal De Physique Colloques 1983, 44. DOI: 10.1051/jphyscol:1983678.

4. Zhang, D.; Li, C.; Zhang, C.; Slipchenko, M. N.; Eakins, G.; Cheng, J.-X. Depth-Resolved Mid-Infrared Photothermal Imaging of Living Cells and Organisms with Submicrometer Spatial Resolution. Sci. Adv. 2016, 2 (9). DOI: 10.1126/sciadv.160052

5. Yin, J.; Zhang, M.; Tan, Y.; Guo, Z.; He, H.; Lan, L.; Cheng, J.-X. Video-Rate Mid-Infrared Photothermal Imaging by Single-Pulse Photothermal Detection per Pixel. Sci. Adv. 2023, 9 (24). DOI: 10.1126/sciadv.adg8814

6. Ji-Xin Cheng Group, Boston University website. https://sites.bu.edu/cheJng-group/the-pi/ (accessed 2024-07-15)

7. Wang, H.; Fu, Y.; Cheng, J. X. Experimental Observation and Theoretical Analysis of Raman Resonance Induced Photodamage in Coherent Anti-Stokes Raman Scattering Microscopy. J. Op. Soc. Am. B, 2007, 24, 544-552. DOI: 10.1364/JOSAB.24.000544

8. Dong, P.-T.; Mohammad, H.; Hui, J.; Leanse, L. G.; Li, J.; Liang, L.; Dai, T.; Seleem, M. N.; Cheng, J.-X. Photolysis of Staphyloxanthin in Methicillin-Resistant Staphylococcus aureus Potentiates Killing by Reactive Oxygen Species. Adv. Sci. 2019, 6 (11), 1900030. DOI: 10.1002/advs.201900030

Ji-Xin Cheng attended University of Science and Technology of China (USTC) from 1989 to 1994. From 1994 to 1998, he carried out his PhD study on bond-selective chemistry at USTC. As a graduate student, he worked as a research assistant at Universite Paris-sud (France) on vibrational spectroscopy and the Hong Kong University of Science and Technology (HKUST) on quantum dynamics theory. After postdoctoral training on ultrafast spectroscopy at HKUST, he joined Sunney Xie’s group at Harvard University as a postdoc, where he spearheaded the development of CARS microscopy that allows high-speed vibrational imaging. Cheng joined Purdue University in 2003 as Assistant Professor in Weldon School of Biomedical Engineering and Department of Chemistry, promoted to Associate Professor in 2009 and Full Professor in 2013. He joined Boston University as the Inaugural Theodore Moustakas Chair Professor in Photonics and Optoelectronics in summer 2017.

Authored in 330 peer-reviewed articles with an h-index of 101 (Google Scholar) and holder of >30 patents, Cheng and his team has been constantly at the most forefront of the chemical imaging field in development, discovery, and delivery. Among his honors, Cheng is the recipient of the 2024 Analytical Chemistry Spectrochemical Analysis Award from American Chemical Society,the 2024 Charles Delisi Award from Boston University College of Engineering, the 2024 Biophotonics Technology Innovator Award from International Society for Optics and Photonics (SPIE), the 2022 Boston University Innovator of Year, the 2020 Pittsburgh Spectroscopy Award from the Spectroscopy Society of Pittsburgh, the 2019 Ellis R. Lippincott Award from Optica, Society for Applied Spectroscopy, and Coblentz Society, the 2016 Research Award from Purdue University College of Engineering, and the 2015 Craver Award from Coblentz Society.