Rapid, high throughput acquisition of 3D morphology of single cells

Contact PD/PI: LEE, ABRAHAM My research focuses on the development of novel microfluidic tools for precision medicine, including cell sorting and enrichment, single cell analyses, cell-cell interactions, cell engineering, artificial cells, and vascularized micro organs. Over the years my lab has developed a versatile set of microfluidic platforms for biological applications: 1. droplet microfluidics for molecular and cellular analysis, 2. acoustic microstreaming for sample preparation, cell sorting, and rare cell enrichment, 3. dielectrophoresis (DEP) for label-free separation and enrichment of targeted cell populations, 4. microfluidic platforms for single cell analysis and vascularized organs-on-a-chip. Based on these techniques, the three major projects currently in my lab are: (1) acoustic- electric shear orbiting poration (AESOP) platform that modulates acoustic and electric fields to induce size- controlled membrane pores for non-viral intracellular delivery (NIGMS (R01GM145987-01). The AESOP device has allowed us to control dosage and sequentially deliver multiple genetic coding cargoes into cells efficiently and gently. (2) artificial antigen presenting cells (aAPCs) with conjugated targeting ligands that form cell-to-cell synapses for antigen-specific T cell activation (R33CA267258-01A1). This aAPC platform enables the de novo design of cells for various research applications with potential biomedical applications in cell therapy for cancer, autoimmune diseases, and even Alzheimer’s Disease. (3) arrayed-droplet optical projection tomography (ADOPT) platform capable of capturing the 3D morphology of single cells both of the membrane as well as the intracellular organelles. This platform is the driver for this grant and will provide rich biological content for cellular studies. For the next 5 years, we will tackle challenging biological questions and bottlenecks in the field: 1. Can we rapidly acquire a panel of 3D single cell morphology with a drop of blood? 2. How does 3D single cell morphology correlate with existing single cell analysis tools such as dropseq? 3. How does 3D morphology of cell membrane and intracellular organelles correlate to cell function and cell state? 4. How does shear force affect 3D morphology and mechanosensitive pathways? 5. Can one precisely program cells for specific cell function or cell state? 6. Can 3D single cell profiling (size, shape, morphology) of immune cells and tumor cells reveal comprehensive health status (immune health, metabolic health)? The vision of the CPU for cell-based health assessment and intervention: The bioengineering “CPU” (cell processing unit) is analogous to the CPU (central processing unit) for computer engineering. The bio-CPUs are microfluidic processors capable of cell sorting, cell engineering, and cell sensing. This MIRA grant provides a “GPU” (graphics processing unit) by producing 3D morphologies of single cells that will be powered by the bio- CPUs. This is how the AI revolution was started and how the BI (biological intelligence) revolution may lie. Project Number: 1R35GM161681-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Abraham Lee | Institution: UNIVERSITY OF CALIFORNIA-IRVINE, IRVINE, CA | Award Amount: $493,884 | Activity Code: R35 | Study Section: Special Emphasis Panel[ZRG1 MCST-Q (55)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11261007