Methods
We development experimental methods to investigate molecular states of each cell in its original spatial context.
Deep Dye Drop
The Dye Drop assay is a versatile, low-cost, multiplexed microscopy method for obtaining detailed single-cell viability and cell cycle data. The Dye Drop method uses a set of incrementally more dense solutions to prevent cell loss and improve the consistency of cell perturbation experiments. Dye Drop can also be combined with CyCIF to yield further molecular and spatial information. The method is paired with computational analysis tools that calculate cell state and growth rate metrics from the high throughput data.
Orion
Orion is a method for collecting one-shot 18-plex immunofluorescence images and diagnostic-grade H&E images from the same samples. The Orion method was developed in collaboration with RareCyte Inc. and uses a specialized microscope and fluorescent antibodies (known as ArgoFluors™), which can be imaged simultaneously and spectrally unmixed. We show that same-slide H&E and IF images provide complementary information that can be used to train ML models that effectively predict cancer progression.
CyCIF
CyCIF (cyclic immunofluorescence) is a robust and inexpensive method for highly multiplexed immunofluorescence imaging using standard instruments and reagents. t-CyCIF generates multiplexed images of fixed, paraffin-embedded (FFPE) samples using an iterative process in which conventional low-plex fluorescence images are repeatedly collected from the same sample and then assembled into a high dimensional representation. Highly multiplexed images of intact tumor architecture can be used to quantify signal transduction cascades, measure the levels of tumor antigens, determine precise immune phenotypes, and more.
Pick-Seq
Pick-Seq is a form of micro-region sequencing in which small regions of tissue, containing 5-20 cells, are mechanically isolated on a microscope and then sequenced. Pick-Seq is compatible with several different fixed and frozen human specimens. It provides deep transcriptional profiling in the spatial contex and can be integrated with other spatial omics methods to achieve a hollistic view of the biology.