Research

In the Schultz Lab, we believe the new scientific breakthroughs will be enabled by state of the art chemical measurement. Our research focuses on developing new tools for identifying molecules relevant to biomedical diagnostics and other applications.  To do this, we build and develop instrumentation that takes advantage of chemical properties to characterize complex samples.  The interaction between lasers and molecules provides unique information for detecting and identifying the components in complex systems.  Understanding the basic science involved in chemical detection and manipulating these interactions has led to breakthrough technologies with tremendous potential.

CHEMICAL DETECTION AND IMAGING.. The ability to visualize and detect molecules can provide new insight into their function, serve as biomarkers for disease, and illustrate how local changes and alter reactions.  Label-free methods of detection can further elucidate native and complex environments in a non-destructive manner.  We are interested in using vibrational spectroscopies, such as Raman and Infrared, to detect, monitor, and image chemical behavior in complex systems.  We are developing instrumentation and methodology that enables trace detection down to single molecule levels and super-resolution imaging on the nanometer length scale.  These advances in instrumentation and methodology are poised to address research questions that challenge current techniques.

 

References for further reading:

  • Shoup DN, Scarpitti BT, Schultz ZD*. A Wide-Field Imaging Approach for Simultaneous Super-Resolution Surface-Enhanced Raman Scattering Bioimaging and Spectroscopy. ACS Measurement Science Au. 2022, 2 (4), 332-341. doi: 10.1021/acsmeasuresciau.2c00013.
  • Schorr, H.C.; Schultz, Z.D.* Digital surface enhanced Raman spectroscopy for quantifiable single molecule detection in flow. Analyst 2024, 149, 3711-3715, DOI: 10.1039/D4AN00801D.
  • Scarpitti, B. T.; Fan, S.; Lomax-Vogt, M.; Lutton, A.; Olesik, J. W.; Schultz, Z. D.* Accurate Quantification and Imaging of Cellular Uptake Using Single-Particle Surface-Enhanced Raman Scattering. ACS Sensors 2024, 9 (1), 73-80. DOI: 10.1021/acssensors.3c01648.
  • Rist, D.; DePalma, T.; Stagner, E.; Tallman, M. M.; Venere, M.; Skardal, A.; Schultz, Z. D.* Cancer Cell Targeting, Magnetic Sorting, and SERS Detection through Cell Surface Receptors. ACS Sensors 2023, 8 (12), 4636-4645. DOI: 10.1021/acssensors.3c01625
  • Lifu Xiao; Chuanqi Wang; Chen Dai; Laurie Littlepage; Jun Li; Zachary Schultz*, Untargeted Tumor Metabolomics with Liquid Chromatography—Surface-Enhanced Raman Spectroscopy. Angewandte Chemie Int. Ed. 2020, 59 (9), 3439-3443, DOI: 10.1002/anie.201912387

MACHINE LEARNING FOR SPECTROSCOPIC SENSORS.  Vibrational spectroscopy yields intrinsic multivariate data that can be used to model complex biological and physical phenomena. The analysis of this data using machine learning (ML), and potentially generative AI algorithms offers new ways to leverage these measurements to solve complex research questions.  We are currently using applying and exploring how ML can improve analysis in number of applications.  In many of these examples, spontaneous Raman or infrared spectra are modeled to determine complex behavior.

 

References for further reading:

  • Poonia, M.; Witte, S.A.; Woodward, M.; Yadav, P.; Puri, S.; Santhanam R.; Jacob N.K.; Schultz Z.D.* Raman investigation of in vivo radiation exposure on melanin in murine hair. PNAS Nexus. 2025;4(4). doi: 10.1093/pnasnexus/pgaf108.
  • Rist, B. L.; Witte, S. A.; Schultz, Z. D.* Machine Learning Classification of Integrin-Expression-Based Magnetic Sorted SW 620 Cells by Simultaneous O-PTIR and SERS. Anal. Chem. 2024, 96 (43), 17184-17191. DOI: 10.1021/acs.analchem.4c02685.
  • Witte, S.A.; Poonia, M.; Woodward, M.; Lu, L.; Yadav, M.; Jacob, N.K.; Schultz, Z.D.* Raman Spectroscopic Biodosimetry Using Protein in Murine Hair. Radiation Research. 2025. IN PRESS doi: 10.1667/rade-25-00046.1.

ACTIVE PLASMONICS. Underlying all the problems we investigate is the basic science relevant to the signal enhancements incorporated into our measurements.  We are interested in understanding how nanomaterials interact with light, particularly with respect to how these properties alter the response from nearby molecules. This basic science serves as the basis for the development of future measurement techniques and other applications, such as photo-catalysts.

References for further reading:

  • Fan, S.*†; Cheng, R.†; Lin, H.†; Luo, Z.;  Smith, A.E.; Wang, C.; He, J.; Scarpitti, B.T.; Shoup, D.N.; Schorr, H.C.; Liang, E.; Ye,J.; Cheng, J.X.*; Schultz, Z.D.* Single-particle surface-enhanced coherent anti–Stokes Raman scattering: Nanoparticle design and mechanism. Science Advances 2026. 12(5) eady0545, doi: 10.1126/sciadv.ady0545
  • Fan, S.; Scarpitti, B.T.; Smith, A.E.; Luo, Z.; Ye, J.; Schultz, Z.D. Linker-Free Synthesis of Core/Satellite Nanoparticles for Single-Particle Surface-Enhanced Raman Spectroscopy and Photocatalysis. Nano Lett. 2025. IN PRESS doi: 10.1021/acs.nanolett.5c00763.
  • Landaeata, E.; Kadosh, N.; Schultz, Z.D., Mechanistic Study of plasmon assisted in situ photoelectrochemical CO2 reduction to acetate with a Ag/Cu2O nanodendrite electrode. ACS Catalysis 2023, 13, 1638-1648. doi: 10.1021/acscatal.2c05082
  • Nelson, D.A. and Schultz, Z.D.*, “Influence of Optically Rectified Electric Fields on the Plasmonic Photocatalysis of 4-Nitrothiophenol and 4-Aminothiophenol to 4,4-Dimercaptoazobenzene”, Journal of Physical Chemistry C, 2018, 122(15), 8581-8588, DOI: 10.1021/acs.jpcc.8b00662.
  • Zeng, Z., Wang, H., Johns, P., Hartland, G.V., and Schultz, Z.D.*, “Photothermal Microscopy of Coupled Nanostructures and the Impact of Nanoscale Heating in Surface Enhanced Raman Spectroscopy”, Journal of Physical Chemistry C, 2017, 121(21), 11623-44631, DOI: 10.1021/acs.jpcc.7b01220.
  • Wang, H., Yao, K., Parkhill, J.A.*, and Schultz, Z.D.* “Detection of electron tunneling across plasmonic nanoparticle-film junctions using nitrile vibrations”, Physical Chemistry Chemical Physics, 2017, 19(8), 5786-5796, DOI: 10.1039/C6CP08168A.
  • Kwasnieski, D.T.; Wang, H.; Schultz, Z.D.*, “Alkyl-Nitrile Adlayers as Probes of Plasmonically Induced Electric Fields.” Chemical Science, 2015.6(8), 4484 – 4494, DOI: 10.1039/C5SC01265A.
  • Marr, J.M., Schultz, Z.D.*, “Imaging Electric Fields in SERS and TERS Using the Vibrational Stark Effect” J. Physical Chemistry Letters, 2013, 4(19), 3268-3272, DOI: 10.1021/jz401551u.