Spatial-temporal transcriptomics via nanofabricated pillar arrays

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Speaker
Dr. Bokai Zhu, postdoctoral researcher at MIT
Location
Institute for Soldier Nanotechnologies (NE47-189)
Open to
MTL Community

Abstract: Current spatial-omics methods are inherently destructive, capturing molecular states at a single time point and limiting access to dynamic cellular processes. Here, I present ongoing work to develop nanopillar-based interfaces for minimally perturbative, spatiotemporal molecular sampling from live cells and tissues. Building on prior demonstrations that nanopillars can transiently penetrate cell membranes without compromising viability, we engineer silicon nanopillar arrays functionalized with capture oligonucleotides to sample intracellular RNA in situ. I will describe optimization of key physical and experimental parameters-including pillar geometry, array density, surface chemistry, and stamping dynamics-and benchmarks for cell survival, stress responses, and capture efficiency. In parallel, we are implementing spatial barcoding strategies to register captured transcripts to their sampling locations with micron-scale accuracy. Together, this platform aims to enable repeated, multiplexed molecular readouts from the same living tissue over time, providing a foundation for studying dynamic immune and tissue-level processes beyond static endpoint measurements.

Bio: I received my PhD from the Department of Microbiology and Immunology at Stanford University, where I trained with Professor Garry Nolan. My research focuses on integrating experimental and computational approaches in systems immunology to study tissue biology in disease contexts. On the computational side, I develop algorithms for cross-modality single-cell data integration; on the experimental side, I develop multiplex imaging assays to detect viruses and microbiota within complex host–tissue environments. This interdisciplinary training has equipped me with complementary skill sets spanning molecular method development, animal models, clinically relevant sample analysis, and rigorous statistical and mathematical modeling. Working at the interface of computation and experimentation has enabled me to initiate and lead collaborative projects across institutions including MIT, Stanford, Harvard, and Yale, collaborating closely with both early-career and established investigators.