Research

Accelerated Drug Discovery: Instrumentation, Synthesis, and Analysis

Drug discovery using a conventional synthetic approach is a lengthy and costly process that involves sequential reactions from starting materials (de novo synthesis). As an alternative, mass spectrometry (MS) combined with automation could be an important high-throughput (HT) synthetic and screening tool. The synthesis can be performed in microdroplets generated during ESI-MS analysis, where the chemical reactions are found to be ~102-106 times faster than the conventional bulk-phase reaction. HT reaction screening will help build a library of functionalized drugs, in which thousands or millions of drug compounds are rapidly screened. The modified drug library will be further tested using bioassays to identify the most efficient drug. The entire workflow (from synthesis to analysis) will be automated and is intended to be cost-effective by eliminating the cumbersome process of the traditional drug discovery approach.

Microdroplet-Promoted Materials Synthesis

Materials synthesis is a cornerstone of chemistry; however, the traditional approach involves technical challenges, such as precision over composition and structure, synthetic throughput, sustainability concerns for using toxic solvents, and high energy inputs. As an alternative, our goal is to utilize electrospray deposition (ESD) of microdroplets containing precursors, where a much higher chemical specificity of materials and precision can be achieved. This microdroplet-promoted synthesis has considerable advantages over traditional methods, providing control over the chemical identity, morphology, thickness, and surface patterning of materials while avoiding high temperatures, additives, ligands, and reducing agents. Furthermore, it will provide considerable opportunities to optimize materials for applications such as catalysts, electronic devices, batteries, and sensors.

Automated Biomarker Discovery by Mass Spectrometry Imaging

The spatial distribution of molecular species in a sample is crucial for gaining key insights into biological, chemical, and physiological processes. Mass spectrometry imaging (MSI) has emerged as an important label-free bioanalytical tool that provides the spatial distribution of biomarkers in biological samples. We plan to utilize an automated HT-DESI-based MSI scanning of the tissue surface to record the mass spectrum from each spot, which will finally be processed into an image based on the ion intensity of biomarker analytes. In addition, we will also look for novel biomarkers that can be used to understand the disease state of the sample.

Investigation of the Origin of Life in Microdroplets

Recent research suggests that atmospheric aerosols/microdroplets act as prebiotic chemical reactors that synthesize biological molecules in the absence of enzymes. However, a sound understanding of the catalytic role of microdroplets in biopolymerization is lacking. We are interested in exploring the catalytic role of atmospheric aerosols in polypeptide formation using ambient mass spectrometry analysis. We plan to study aerosols/microdroplets of the appropriate dimensions through electrospray, the Leidenfrost effect, acoustic, and aerodynamic levitation. All these phenomena, along with the analysis of key reactive intermediates, will help reveal the mystery of the origin of life occurring in atmospheric aerosols or microdroplets.

Bridging Microdroplets with Atmospheric Chemistry

New particle formation (NPF) is the source for ~50% of global cloud condensation nuclei (CCN) formation, substantially affecting cloud properties and Earth’s energy balance. The organic-mediated NPF nucleation is poorly understood due to the low abundances of organic compounds in most regions and the lack of high-resolution analytical tools. We are eager to understand the role of volatile organic compounds (VOCs) and secondary organic aerosols (SOA) in NPF nucleation by high-resolution ambient mass spectrometry, which is ideally suited due to its high sensitivity and molecular specificity. With a prior understanding of microdroplet chemistry, we will assess the effects of temperature, relative humidity, pH, stoichiometric ratio, and concentrations, and will also correlate the results with the data obtained from direct field studies from different environments, such as rural, urban, ocean, and forest regions at different altitudes, for a holistic understanding of the mechanisms behind NPF.