NIH Grant Supports Technology Capable of Taking 3D Snapshots of Single Cells for Personalized Medicine
April 30, 2026 - Principal investigator: Abraham Lee, Chancellor’s Professor of biomedical engineering
Award: $2.2 million over five years
Funding agency: NIH National Institute of General Medical Sciences
Project: Rapid, High Throughput Acquisition of 3D Morphology of Single Cells
The COVID-19 pandemic showed that some people are more susceptible to infection than others and that the effectiveness of vaccination and treatment also depends heavily on the immune status of the individual. What if one could develop a kaleidoscope-like device to take a snapshot of the immune system? This grant aims to develop the capability to rapidly capture 3D images of single cells, in particular suspended cells such as white blood cells. It is hypothesized that 3D morphology of both the cell membranes and the intracellular organelles will be a powerful health indicator for early detection of diseases, disease progression and treatment tracking. This is because the size, shape and roughness of the cell membrane reflect the composite state of the cell’s physiological or pathological status. There is also evidence that the contour and shape of the chromatin containing the genome is indicative of the genes being expressed and regulated. In addition to precision diagnostics, the 3D morphology of a large population of cells can be gleaned to optimize the engineering of cells for various therapeutic biologics such as monoclonal antibodies and cell-based immunotherapies.
This grant will further develop a microfluidic technology developed in the Lee lab, termed Arrayed Droplet Optical Projection Tomography (ADOPT). ADOPT utilizes oil flow-induced shear to generate microvortices within cell-laden droplets. This allows for the continuous rotation of encapsulated cells for 3D capturing of cell surface topography and its intracellular components, enabling a highly parallelized method of imaging live suspension cells. The main technical challenges to be tackled by this grant include automating the microfluidic platform for high-speed single cell profiling and the precision delivery of immunolabeling molecules for multiplexed intracellular morphology imaging.
More information: https://www.pnas.org/doi/10.1073/pnas.2408567121