Capillaric microfluidics for integrated, self-powered, and self-regulated sample preparation in miniaturized mass spectrometry systems

The National Institute of General Medical Sciences (NIGMS) awarded a $427,625 Project Grant to the University of Washington, effective September 1, 2025, through August 31, 2030, under the Biomedical Research and Research Training program (CFDA 93.859). This award supports the development of capillaric microfluidics technology for integrated, self-powered, and self-regulated sample preparation in miniaturized mass spectrometry (MS) systems. The research addresses a critical gap in miniaturized MS capabilities by leveraging 3D-printed capillaric microfluidics to enable rapid prototyping and reduce instrumentation complexity, thereby improving matrix tolerance, accuracy, precision, and versatility of portable MS instruments for decentralized diagnostic applications.

The project delivers advanced analytical infrastructure and methodological capabilities that facilitate real-time biochemical analysis and diagnostics in resource-limited environments, with direct applications to point-of-care disease biomarker monitoring, therapeutic drug level assessment, and metabolic state evaluation. This research aligns with NIGMS priorities in advancing precision medicine and fundamental biomedical research by enabling deployment of sophisticated analytical tools in clinical and field settings where conventional mass spectrometry systems are impractical, ultimately supporting timely medical interventions and improved public health outcomes.

Abstract

Mass spectrometry (MS) stands as a cornerstone of analytical techniques used across various fields of biological and chemical sciences. Its ability to provide detailed molecular information makes IT indispensable for both basic and applied research. Miniaturized mass spectrometers offer significant benefits in areas relevant to nigms priorities by enabling rapid, on-site biochemical analysis and diagnostics in resource-limited or decentralized environments, which can advance precision medicine, public health, and fundamental biomedical research. Their portability allows for real-time monitoring of disease biomarkers, therapeutic drug levels, and metabolic states directly at the point of care, facilitating timely interventions. While miniaturized MS systems excel in portability and real-time analysis, they typically lack the versatility and thorough sample separation of conventional systems, limiting their applicability to a narrower range of sample types. Integrated sample preparation strategies that improve the matrix tolerance, accuracy, precision, and versatility of miniaturized MS instruments are crucial to address the growing need for decentralized diagnostic tools in both clinical and field environments. Microfluidics offer precise control, reduced sample volumes, and improved reproducibility, and are a promising platform for automated sample preparation. However, current microfluidic approaches have complexity and cost issues. 3D- printed capillaric microfluidics present a promising solution. They allow rapid prototyping and eliminate the need for complex instrumentation, making them accessible to non-experts and diverse scientific fields. The overarching goal of this ESI mira grant is to develop capillaric microfluidics for integrated sample preparation in mini-MS systems. The research will focus on three broad research areas that align with nigms's mission of advancing basic biological processes and translational applications, namely: (1) integrating capillaric microfluidics with mini-MS cartridges and ionization systems, (2) automating dried reagent rehydration and addition of internal standards and derivatization agents, and (3) implementing solid phase extraction and assay validation with clinical samples. The detection of antiretroviral drugs and a comparison with traditional MS will be used as a proof-of-concept to demonstrate accuracy and precision of the developed technologies. This project aims to revolutionize sample preparation in mini-MS, making IT more accurate, precise, and versatile, and ultimately benefiting scientific research and diagnostics. The PI has a strong background in bioengineering and has made key contributions to the design, 3D-printing, and applications of capillaric microfluidics. This project has the potential to uncover new long-term directions and innovations both in the development of microfluidic technologies and their application to a wide a variety of fields.