Ji-Xin Cheng | |
---|---|
Nationality | American |
Education | Bachelor of Science Doctor of Philosophy |
Alma mater | University of Science and Technology of China (B.S. in 1994, PhD in 1998) |
Known for | Chemical imaging |
Scientific career | |
Fields | Biophotonics |
Institutions | Boston University (2017–present) Purdue University (2003–2017) |
Thesis | Bond-selective Chemistry: from Local Mode Vibration to Optimal Control of Molecular Dynamics by Laser |
Doctoral advisor | Qingshi Zhu |
Ji-Xin Cheng is an academic, inventor, and entrepreneur. He holds the Moustakas Chair Professorship in Optoelectronics and Photonics at Boston University. [1] His inventions span optical imaging, cancer diagnosis, neuromodulation, and phototherapy of infectious diseases. He holds positions of co-founder of Vibronic [2] and of Pulsethera. [3] He is also the scientific advisor of Photothermal Spectroscopy [4] and Axorus. [5]
Cheng is most known for his development of chemical imaging techniques, [6] focusing on molecular spectroscopic imaging in technology development, life science applications, and clinical translation. [7] His work has been recognized by the 2019 Ellis R. Lippincott Award from Optica, [8] the 2020 Pittsburgh Spectroscopy Award from the Spectroscopy Society of Pittsburgh, [9] and the 2024 SPIE Biophotonics Technology Innovator Award from International Society for Optics and Photonics. [10]
Cheng is a Fellow of Optica (the Optical Society of America) [11] and the American Institute for Medical and Biological Engineering. [12]
Cheng obtained a Bachelor of Science degree from the University of Science and Technology of China in 1994. Later, he obtained a PhD in 1998 from the same institution. After completing his PhD, Cheng had one-year postdoc training at the University of Science and Technology of Hong Kong (1999). [1] From 2000 to 2003, he joined Sunney Xie's lab at Harvard University as a postdoc, where he and others worked on the development of coherent anti-Stokes Raman scattering (CARS) microscopy. [13]
In 2003, he joined Purdue University as assistant professor in the Weldon School of Biomedical Engineering and Department of Chemistry. He was promoted to Associate Professor in 2009 and to professor in 2013. [14] In 2017, he was recruited to Boston University as the inaugural Moustakas Chair Professor in Optoelectronics and Photonics in the Departments of Electrical and Computer Engineering and Biomedical Engineering. [1]
Since 2021, he has served as the Director of the Boston University Photonics Center Graduate Student Initiative. [15]
Cheng has co-founded companies, including Vibronix, in 2014, [2] and Pulsethera, in 2019. [3] He holds the position of scientific advisor at Photothermal Spectroscopy Corp. in Santa Barbara, California, and at Axorus in Paris.
Cheng has authored 300+ peer-reviewed publications spanning the areas of coherent Raman microscopy, mid-infrared photothermal microscopy, transient absorption microscopy, electromagnetic and ultrasound waves for neutral modulation, phototherapy of infectious diseases, as well as medical applications of nanomaterials. [7]
Cheng's research has focused on coherent anti-Stokes Raman scattering (CARS) microscopy across various aspects such as instrumentation, theory, and practical applications. His research introduced concepts like CARS microscope using picosecond excitation, [16] epi-detected CARS, [17] and polarization-sensitive CARS. [18] In 2002, he created a Green's function model that elucidates the contrast mechanism in CARS microscopy. [19] Additionally, he led the development of laser-scanning CARS integrated into a confocal microscope. [20] At Purdue University, his group led the development of multimodal nonlinear optical imaging using a CARS microscope. [21]
From 2013 onward, Cheng and his research team devised methods that allow for the rapid acquisition of Raman spectra at microsecond time scale per pixel, facilitating vibrational spectroscopic imaging of live organisms. One notable achievement includes the creation of a tuned amplifier array, [22] which enabled the development of the speediest Raman spectroscopic imaging system, capable of capturing a Raman spectrum in just 5 microseconds. [23] His team further developed frameworks for transforming hyperspectral data into chemical maps of prominent substances. Through vibrational spectroscopic imaging on human patient samples, Cheng and his collaborators identified cholesteryl ester as a pervasive metabolic indicator of highly malignant cancers. [24] [25]
In 2011, Cheng and coworkers introduced overtone photoacoustic microscopy, which combined optical excitation of overtone vibration and acoustic detection of pressure transients to enable label-free bond-selective imaging of deep tissues. [26] In collaboration with Professor Michael Sturek at the Indiana University School of Medicine, his team developed intravascular vibration-based photoacoustic catheters that can perform video rate imaging of lipids in an arterial wall. In 2014, he co-founded Vibronix aiming to further develop vibrational imaging technologies into commercial microscopes and medical devices. In 2020, Vibronix received FDA approval for their first medical device, AcuSee, for ultrasound image-guided surgical removal of kidney stones. [27]
In 2016, his team introduced a mid-infrared photothermal (MIP) imaging technique that overcame the limitations of traditional infrared spectroscopic imaging, achieving micromolar detection sensitivity and submicrometer spatial resolution for three-dimensional chemical imaging of live cells and organisms. [28] Concentrating on optical photothermal IR imaging, his research group have made contributions to technology advancement through a series of innovations. These innovations encompass widefield MIP, [29] optical phase detection, [30] and fluorescence detection. [31] His recent invention, single pulse digitization, [32] has facilitated real-time super-resolution infrared chemical imaging of living organisms at video rate. [33] In 2024, his group reported in Nature Methods a mid-infrared photothermal reporter for imaging enzymatic activities in live cells. [34]
In 2017, Photothermal Spectroscopy, with Cheng as a Scientific Advisor, announced mIRage, a commercial microscope for mid-infrared photothermal imaging. [35]
In addition to his research on bond-selective chemical imaging, Cheng also made advancements in the field of high-resolution and high-speed transient absorption (TA) microscopy. In 2013, his team pioneered far-field super-resolution transient absorption imaging, breaking the conventional diffraction limit by achieving a spatial resolution of 200 nm through controlled electronic absorption saturation. [36] On the applications of TA spectroscopic imaging, his team was the first to use phase-sensitive TA imaging to distinguish metallic from semiconducting carbon nanotubes. [37] They also tracked single-walled carbon nanotubes in living cells using this method. [38] In 2019, they developed a technique combining TA spectroscopic imaging and phasor analysis to quantify HbA1c levels within individual red blood cells. [39] His group also unveiled a metabolic shift in melanoma from pigment-rich to lipid-rich as it progresses from primary to metastatic stages, potentially advancing the detection and treatment of this aggressive skin cancer. [40]
Beyond Chemical Imaging, Cheng's research revolves around developing a set of tools designed to control cellular activity using electromagnetic or ultrasound waves. His group created a fiber optoacoustic emitter that transforms laser pulses into an extremely focused ultrasound field at the tip of the fiber, enabling precise stimulation of neurons at submillimeter accuracy and single-cell stimulation using a tapered fiber setup. [41] His team further expanded on their work to create a non-invasive brain modulation technique using optically generated focused ultrasound with extremely precise spatial targeting. [42] Additionally, he and coworkers created a microwave split ring resonator to generate gap-based ultrasound. [43] This device enables precise neural activity inhibition beyond the microwave's diffraction limit.
Under a lab-built transient absorption microscope, Cheng and his student Pu-Ting Dong accidentally found fast photobleaching of staphyloxanthin, a chromophore in methicillin-resistant S. aureus (MRSA). He converted this failed imaging experiment into a therapy for the super-bug MRSA by synergizing the pigment photobleaching with hydrogen peroxide and conventional antibiotics. [44] Cheng, along with his coworkers, further discovered that certain wavelengths of light can deactivate natural light-absorbing molecules in a broad spectrum of bacteria and fungi, enabling the development of a therapy that sensitizes drug-resistant infections to low levels of hydrogen peroxide. [45]
In his early career, Cheng explored medical applications of nanomaterials including gold nanorods and polymer micelles. His 2005 paper in PNAS indicates that gold nanorods, when excited at 830 nm, exhibit strong two-photon luminescence with polarization dependence, plasmon-enhanced absorption, and higher signal intensity than traditional fluorescent probes, making them promising candidates for in vivo imaging applications. [46]
In 2007, Cheng and collaborators investigated the photothermal effects of gold nanorods on tumor cells [47] and established that plasmon-resonant gold nanorods, with carefully modified surface chemistry, have the potential for use in image-guided therapies based on localized hyperthermia at low laser fluences. [48] His 2009 work highlighted the versatility of gold nanorods in the biomedical field, emphasizing their unique optical properties, surface chemistry control, and potential for both imaging and therapeutic applications, particularly in the context of cancer treatment. [49] In 2010, his team described in Nature Nanotechnology a membrane repair property of block co-polymer micelles and showed its effectiveness in repairing traumatic spinal cord injury. [50]
Microscopy is the technical field of using microscopes to view objects and areas of objects that cannot be seen with the naked eye. There are three well-known branches of microscopy: optical, electron, and scanning probe microscopy, along with the emerging field of X-ray microscopy.
Spectroscopy is the field of study that measures and interprets electromagnetic spectrum. In narrower contexts, spectroscopy is the precise study of color as generalized from visible light to all bands of the electromagnetic spectrum.
Raman spectroscopy is a spectroscopic technique typically used to determine vibrational modes of molecules, although rotational and other low-frequency modes of systems may also be observed. Raman spectroscopy is commonly used in chemistry to provide a structural fingerprint by which molecules can be identified.
The term biophotonics denotes a combination of biology and photonics, with photonics being the science and technology of generation, manipulation, and detection of photons, quantum units of light. Photonics is related to electronics and photons. Photons play a central role in information technologies, such as fiber optics, the way electrons do in electronics.
In chemistry and physics, Raman scattering or the Raman effect is the inelastic scattering of photons by matter, meaning that there is both an exchange of energy and a change in the light's direction. Typically this effect involves vibrational energy being gained by a molecule as incident photons from a visible laser are shifted to lower energy. This is called normal Stokes-Raman scattering.
Coherent anti-Stokes Raman spectroscopy, also called Coherent anti-Stokes Raman scattering spectroscopy (CARS), is a form of spectroscopy used primarily in chemistry, physics and related fields. It is sensitive to the same vibrational signatures of molecules as seen in Raman spectroscopy, typically the nuclear vibrations of chemical bonds. Unlike Raman spectroscopy, CARS employs multiple photons to address the molecular vibrations, and produces a coherent signal. As a result, CARS is orders of magnitude stronger than spontaneous Raman emission. CARS is a third-order nonlinear optical process involving three laser beams: a pump beam of frequency ωp, a Stokes beam of frequency ωS and a probe beam at frequency ωpr. These beams interact with the sample and generate a coherent optical signal at the anti-Stokes frequency (ωpr+ωp-ωS). The latter is resonantly enhanced when the frequency difference between the pump and the Stokes beams (ωp-ωS) coincides with the frequency of a Raman resonance, which is the basis of the technique's intrinsic vibrational contrast mechanism.
Near-field scanning optical microscopy (NSOM) or scanning near-field optical microscopy (SNOM) is a microscopy technique for nanostructure investigation that breaks the far field resolution limit by exploiting the properties of evanescent waves. In SNOM, the excitation laser light is focused through an aperture with a diameter smaller than the excitation wavelength, resulting in an evanescent field on the far side of the aperture. When the sample is scanned at a small distance below the aperture, the optical resolution of transmitted or reflected light is limited only by the diameter of the aperture. In particular, lateral resolution of 6 nm and vertical resolution of 2–5 nm have been demonstrated.
Chemical imaging is the analytical capability to create a visual image of components distribution from simultaneous measurement of spectra and spatial, time information. Hyperspectral imaging measures contiguous spectral bands, as opposed to multispectral imaging which measures spaced spectral bands.
Photothermal microspectroscopy (PTMS), alternatively known as photothermal temperature fluctuation (PTTF), is derived from two parent instrumental techniques: infrared spectroscopy and atomic force microscopy (AFM). In one particular type of AFM, known as scanning thermal microscopy (SThM), the imaging probe is a sub-miniature temperature sensor, which may be a thermocouple or a resistance thermometer. This same type of detector is employed in a PTMS instrument, enabling it to provide AFM/SThM images: However, the chief additional use of PTMS is to yield infrared spectra from sample regions below a micrometer, as outlined below.
Photothermal spectroscopy is a group of high sensitivity spectroscopy techniques used to measure optical absorption and thermal characteristics of a sample. The basis of photothermal spectroscopy is the change in thermal state of the sample resulting from the absorption of radiation. Light absorbed and not lost by emission results in heating. The heat raises temperature thereby influencing the thermodynamic properties of the sample or of a suitable material adjacent to it. Measurement of the temperature, pressure, or density changes that occur due to optical absorption are ultimately the basis for the photothermal spectroscopic measurements.
Xiaoliang Sunney Xie is a Chinese biophysicist well known for his contributions to the fields of single-molecule biophysical chemistry, coherent Raman Imaging and single-molecule genomics. In 2023, Xie renounced his U.S. citizenship in order to reclaim his Chinese citizenship.
The Raman microscope is a laser-based microscopic device used to perform Raman spectroscopy. The term MOLE is used to refer to the Raman-based microprobe. The technique used is named after C. V. Raman, who discovered the scattering properties in liquids.
The technique of vibrational analysis with scanning probe microscopy allows probing vibrational properties of materials at the submicrometer scale, and even of individual molecules. This is accomplished by integrating scanning probe microscopy (SPM) and vibrational spectroscopy. This combination allows for much higher spatial resolution than can be achieved with conventional Raman/FTIR instrumentation. The technique is also nondestructive, requires non-extensive sample preparation, and provides more contrast such as intensity contrast, polarization contrast and wavelength contrast, as well as providing specific chemical information and topography images simultaneously.
A localized surface plasmon (LSP) is the result of the confinement of a surface plasmon in a nanoparticle of size comparable to or smaller than the wavelength of light used to excite the plasmon. When a small spherical metallic nanoparticle is irradiated by light, the oscillating electric field causes the conduction electrons to oscillate coherently. When the electron cloud is displaced relative to its original position, a restoring force arises from Coulombic attraction between electrons and nuclei. This force causes the electron cloud to oscillate. The oscillation frequency is determined by the density of electrons, the effective electron mass, and the size and shape of the charge distribution. The LSP has two important effects: electric fields near the particle's surface are greatly enhanced and the particle's optical absorption has a maximum at the plasmon resonant frequency. Surface plasmon resonance can also be tuned based on the shape of the nanoparticle. The plasmon frequency can be related to the metal dielectric constant. The enhancement falls off quickly with distance from the surface and, for noble metal nanoparticles, the resonance occurs at visible wavelengths. Localized surface plasmon resonance creates brilliant colors in metal colloidal solutions.
AFM-IR or infrared nanospectroscopy is one of a family of techniques that are derived from a combination of two parent instrumental techniques. AFM-IR combines the chemical analysis power of infrared spectroscopy and the high-spatial resolution of scanning probe microscopy (SPM). The term was first used to denote a method that combined a tuneable free electron laser with an atomic force microscope equipped with a sharp probe that measured the local absorption of infrared light by a sample with nanoscale spatial resolution.
Tip-enhanced Raman spectroscopy (TERS) is a variant of surface-enhanced Raman spectroscopy (SERS) that combines scanning probe microscopy with Raman spectroscopy. High spatial resolution chemical imaging is possible via TERS, with routine demonstrations of nanometer spatial resolution under ambient laboratory conditions, or better at ultralow temperatures and high pressure.
Cho Minhaeng is a South Korean scientist in researching physical chemistry, spectroscopy, and microscopy. He was director of the National Creative Research Initiative Center for Coherent Multidimensional Spectroscopy and is founding director of the Center for Molecular Spectroscopy and Dynamics in the Institute for Basic Science (IBS), located in Korea University.
Nano-FTIR is a scanning probe technique that utilizes as a combination of two techniques: Fourier transform infrared spectroscopy (FTIR) and scattering-type scanning near-field optical microscopy (s-SNOM). As s-SNOM, nano-FTIR is based on atomic-force microscopy (AFM), where a sharp tip is illuminated by an external light source and the tip-scattered light is detected as a function of tip position. A typical nano-FTIR setup thus consists of an atomic force microscope, a broadband infrared light source used for tip illumination, and a Michelson interferometer acting as Fourier-transform spectrometer. In nano-FTIR, the sample stage is placed in one of the interferometer arms, which allows for recording both amplitude and phase of the detected light. Scanning the tip allows for performing hyperspectral imaging with nanoscale spatial resolution determined by the tip apex size. The use of broadband infrared sources enables the acquisition of continuous spectra, which is a distinctive feature of nano-FTIR compared to s-SNOM. Nano-FTIR is capable of performing infrared (IR) spectroscopy of materials in ultrasmall quantities and with nanoscale spatial resolution. The detection of a single molecular complex and the sensitivity to a single monolayer has been shown. Recording infrared spectra as a function of position can be used for nanoscale mapping of the sample chemical composition, performing a local ultrafast IR spectroscopy and analyzing the nanoscale intermolecular coupling, among others. A spatial resolution of 10 nm to 20 nm is routinely achieved.
Pump–probe microscopy is a non-linear optical imaging modality used in femtochemistry to study chemical reactions. It generates high-contrast images from endogenous non-fluorescent targets. It has numerous applications, including materials science, medicine, and art restoration.
Coherent Raman scattering (CRS) microscopy is a multi-photon microscopy technique based on Raman-active vibrational modes of molecules. The two major techniques in CRS microscopy are stimulated Raman scattering (SRS) and coherent anti-Stokes Raman scattering (CARS). SRS and CARS were theoretically predicted and experimentally realized in the 1960s. In 1982 the first CARS microscope was demonstrated. In 1999, CARS microscopy using a collinear geometry and high numerical aperture objective were developed in Xiaoliang Sunney Xie's lab at Harvard University. This advancement made the technique more compatible with modern laser scanning microscopes. Since then, CRS's popularity in biomedical research started to grow. CRS is mainly used to image lipid, protein, and other bio-molecules in live or fixed cells or tissues without labeling or staining. CRS can also be used to image samples labeled with Raman tags, which can avoid interference from other molecules and normally allows for stronger CRS signals than would normally be obtained for common biomolecules. CRS also finds application in other fields, such as material science and environmental science.
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