(A) Cells are distributed randomly into 96 chambers with no size selection. Enzymatic lysis, DNA denaturation, and whole genome amplification via MDA (Multiple Displacement Amplification) occurs on chip. Amplified DNA is harvested for off-chip library preparations, sequencing, and bioinformatic analyses. (B) Image of a Fluidigm C1 IFC. The polydimethylsiloxane (PDMS) chip is located in the center of a plastic cartridge, which contains wells for inputting cells, reagents, and for harvesting amplified genomic DNA. The cartridge has the dimensions of a standard cell culture plate. Below the image of the C1 IFC, the PDMS microfluidic chip located in the center of the plastic cartridge is enlarged and partially filled with food coloring to illustrate high level organizations of the microfluidic circuit. Each chip contains 96 independent reaction systems split into a mirrored 48 × 2 array, extending from the center channel (filled with red food coloring) to the left and right edges of the chip. The cell loading path (dashed black arrow) and reagent entrance channel (solid green arrow) are denoted. (C) Each reaction system contains one capture chamber and five sequential reaction chambers with different sizes. The first 3 reaction chambers of all reactions systems are filled with food coloring in (B). Two adjacent reaction systems (dashed purple lines in (B) are selected to demonstrate their functions. Red bars represent microfluidic valves whose open and closed states are shown through their cross sections. Green arrows represent flow directions of reagents. All reaction chambers are initially empty (i.e. filled with air). (i) During cell loading, capture chambers are connected and cells are randomly distributed across all capture chambers. Following cell loading, all reaction systems are isolated via valves. Sample images of the microfluidic chambers are shown (black scale bars represent 200 μm). Sequential reactions of (ii) enzymatic lysis to release DNA, (iii) alkaline denaturation and neutralization, and (iii) MDA to amplify DNA are carried out by filling additional empty chambers with reagents. Amplified DNA is flushed into harvest wells for extraction and subsequent off-chip steps.