See-N-Seq — Image-guided Single-Cell RNA Sequencing

Overview

See-N-Seq is a method enabling targeted single-cell RNA sequencing from visually identified cells. It uses micropatterned hydrogel porosity to selectively lyse only the chosen cell while leaving neighboring cells intact.

This bridges what we see under the microscope with what we can sequence, enabling transcriptomic analysis based on morphology or dynamic cellular interactions.

My Role

• Designed and tested the hydrogel patterning method
• Developed single-cell selection workflows
• Performed experimental validation and sequencing pipeline integration
• Co-led manuscript preparation and figure generation

Problem

Conventional single-cell sequencing platforms randomize cell selection, making it impossible to sequence cells based on dynamic biological behaviors (e.g., immune synapse formation).

Approach

Microscopy → Target Cell Identification →

Hydrogel Confinement → Selective Lysis →

mRNA Capture → Sequencing → Analysis

Key Results

• Enabled deterministic targeting of individual cells
• Showed comparable sequencing performance to commercial single-cell workflows
• Demonstrated application to immune conjugate biology

Stack (Research Equivalent)

• Hydrogel micropatterning
• Microscopy + cell-selection algorithms
• RNA-seq library prep
• Data analysis: PCA, clustering, differential expression

Reflection

This project shaped how I think about isolation, signal integrity, and controlled system behavior — concepts that later carried into embedded fault analysis and test automation.