Single Cell Deposition and Patterning with a Robotic System

TLDR

Single‑cell manipulation in biological culture systems is challenging, especially for microfabricated devices that require precise spatial positioning of cells on the device surface. The study introduces a robotic micromanipulation system for pick‑and‑place positioning of single cells. The system uses computer‑vision‑guided motion control with a glass micropipette to pick, transfer, and deposit single cells, exploring whole‑ and partial‑cell aspiration methods. Partial aspiration achieved 15 s per cell with 95 % success, while whole‑cell aspiration took 30 s with 80 % success; the system works across multiple cell types and substrates, and when paired with a parallel technique it raised capture efficiency from ~80 % to 100 %.

Abstract

Integrating single-cell manipulation techniques in traditional and emerging biological culture systems is challenging. Microfabricated devices for single cell studies in particular often require cells to be spatially positioned at specific culture sites on the device surface. This paper presents a robotic micromanipulation system for pick-and-place positioning of single cells. By integrating computer vision and motion control algorithms, the system visually tracks a cell in real time and controls multiple positioning devices simultaneously to accurately pick up a single cell, transfer it to a desired substrate, and deposit it at a specified location. A traditional glass micropipette is used, and whole- and partial-cell aspiration techniques are investigated to manipulate single cells. Partially aspirating cells resulted in an operation speed of 15 seconds per cell and a 95% success rate. In contrast, the whole-cell aspiration method required 30 seconds per cell and achieved a success rate of 80%. The broad applicability of this robotic manipulation technique is demonstrated using multiple cell types on traditional substrates and on open-top microfabricated devices, without requiring modifications to device designs. Furthermore, we used this serial deposition process in conjunction with an established parallel cell manipulation technique to improve the efficiency of single cell capture from ∼80% to 100%. Using a robotic micromanipulation system to position single cells on a substrate is demonstrated as an effective stand-alone or bolstering technology for single-cell studies, eliminating some of the drawbacks associated with standard single-cell handling and manipulation techniques.