To see a world in a grain of sand
And a heaven in a wild flower William Blake Yang’s Group

Enhanced Data Analysis  

MS data contain very rich information. Due to the large sizes and complex structures of the data-sets, performing comprehensive data analysis is very challenging. We have developed effective approaches of using multivariate analysis (e.g., Multivariate Curve Resolution (MCR)) and Machine Learning (ML) to efficiently extract the metabolomics information from metabolomic information from MS images. Similarly, ML based methods have used to analyze SCMS data to extract essential biological information. In addition, we use image fusion technique to integrate optical image (e.g. fluorescence microscopy image) with MS image, allowing for (1) significantly improved spatial resolution and (2) correlation between histological hallmarks (e.g., stained proteins) and metabolomic profiles.

Fundamental Ion Chemistry

Mass spectrometer provides a solvent-free environment for gas-phase ion chemistry study. Simple instrument modifications will allow the introduction of reactant molecules into the mass spectrometer to investigate ion chemistry. Computational chemistry is a rapidly advancing subfield of theoretical chemistry, and provides important supporting and complementary information to experimental results. The combination of modern MS techniques and advanced computational chemistry facilitates research projects that were previously intractable.

Mass Spectrometry Tissue Imaging

Mass spectrometry imaging (MSI) allows for mapping the spatial distribution of a broad range of molecules on surfaces. MSI combines MS with other technologies in microscopy, motion control instrumentation, and software engineering. In general, a MSI measurement is conducted by simultaneously recording the MS data with the physical locations in spot-to-spot scanning way.

The Single-probe MSI setup

Mass Spectrometry Analysis of Live Multicellular Spheroids

3D culture multicellular spheroids are better models for tumors. We produce micro-scale device, the Micro-funnel, that can be implanted into live spheroids to collect metabolites produced from cancer cells. The collected extracellular metabolites can be analyzed by the Single-probe MS technique. The successful development of this technique can benefit the research in microenvironment inside live tissues, cell-cell communication, biomarker discovery, drug development, etc.

Detailed studies of the fragmentation of peptide radical ions can provide additional information on the properties of peptides and proteins, and help the development of new sequencing methodology for proteomics research.

MD simulations

DFT calculations

Structures, energetics,

Reaction mechanisms

Initial structures

Low-energy structures

Research in the Yang laboratory centers on mass spectrometry. We are interested in a variety of areas.

Single Cell Mass Spectrometry Analysis

Traditional cell bioanalysis is performed on samples prepared from large numbers of cells (e.g. cell lysate), such that the information of individual cells is concealed by the averaged results. Single cell mass spectrometry (SCMS) is an emerging field that could potentially revolutionize studies in basic scientific and biomedical research.

Cell approach.wmv

The Single-probe MSI results

• The Single-probe, with a sampling tip smaller than eukaryotic cells (<10 μm), can be inserted into individual living cells to sample the intracellular compounds for immediate MS analysis.

• The Single-probe MS technique has produced highly sensitive detection of intracellular compounds, including cell metabolites, lipids and anticancer compounds, inside living single cells.

• Our research has been highlighted by Chemistry World and C&E News.

Videos of the Single-probe fabrication and applications of live single cell analysis can be found  from: Wei Rao, Ning Pan, Zhibo Yang*, Journal of Visualized Experiments 2016, 112, e53911, (doi:10.3791/53911).

• The Single-probe is a multifunctional device that can also be used for MSI studies to reconstruct the spatial distribution of biomolecules from sections of animal tissues under ambient conditions (i.e. in atmosphere and under room temperature).

We have obtained high spatial resolution (8.5 μm) on biological tissues, which is among the highest resolution that can be obtained using ambient MSI methods (Rao et al. JASMS, 2015, 26, 986).

Photo of mouse kidney slice

MSI of mouse kidney slice

(Spatial resolution 8.5 μm)

Research Funding

External Grants:

(1) ASMS (American Society of Mass Spectrometry) Research Award, 2014 (sponsored by Waters Corporation,       total awarded: $35,000).

(2) OCAST (Oklahoma Center for the Advancement of Science and Technology), Health Research, 2014-2017

     (PI: Zhibo Yang; total awarded: $135,000).

(3) NIH (R01), Aug. 2015-July 2020 (PI: Zhibo Yang; Co-I: Chuanbin Mao; Collaborator: Anthony Burgett;

      total awarded: $1,486,000).

(4) NSF EPSCoRE, May-Aug. 2016 (Co-PI: Zhibo Yang; Co-PI: Marc Libault; total awarded: $5,000)

(5) NIH (R21), June 2016- May 2019 (PI: Anthony Burgett; Co-I: Zhibo Yang; Collaborator: Jonathan Heinlen;

      total awarded: $588,000).

(6) NSF Aug. 2016-Jul. 2019 (PI: Boris Wawrik; Co-PI: Zhibo Yang; total awarded: $462,000)

(7) NIH DSP (Diversity Supplements Program) for minority undergraduate student research, Sept. 2017- Aug.

    2019 (PI: Zhibo Yang; total awarded: $44,000)

Internal Grants:

(1) Faculty Investment Program, OU, 2014, 2015.

(2) Travel Assistance Program, OU, 2013-2016.

(3) Faculty Enrichment Grant, OU, 2013.

(4) Junior Faculty Fellowship, OU, 2013-2014.

(5) VPR Supplemental Equipment Funding, 2013-2014.

(6) OU new faculty startup funding.

Single cells

50 μm

SCMS analysis of HeLa cells using the Single-probe

(Click to watch the video)

Single-probe tip

Research Highlighted in the Media

(1) Interviewed with OCAST radio show, Oklahoma Innovations, for single cell mass spectrometry research,


(2) Single cell mass spectrometry studies has been reported by scientific magazines (Chemistry World and

     C&E News) and websites (Proteo Monitor, Genomeweb, and  Bioanalysis Zone), 2014.

(3) ASMS (American Society of Mass Spectrometry) Research Award, 2014.

(4) Astrochemistry research reported by NCSA (National Center for Supercomputing Applications) and published in

    ACCESS magazine (2011, 24, 10-11) and on the iSGTW (International Science Grid This Week) website.

MS analysis of extracellular metabolites in live spheroids

Principle Component Analysis (PCA) reveals extracellular metabolites are changed by anticancer drug (irinotecan) treatment

Mass Spectrum


Fragment Ion

Fragment Ion

Parent Ion


MSI data analysis using MCR and ML

The Single-probe

The T-probe