New device delivers single cells in just one click

The engineers at SEED Biosciences, an EPFL spin-off, have come up with a unique pipetting robot that can isolate single cells with the push of a button – without damaging the cells. Their device also records the cells’ electrical signature so that they can be traced. While this innovation may seem trivial, it can save researchers several weeks of precious time and speed up development work in pharmaceuticals, cancer treatments and personalized medicine. The company began marketing its device this year.

Creating cell lines from a single cell

Each biological cell – like each human being – is different, with variations in their size, shape and configuration. That has been making researchers’ jobs particularly difficult over the past few years. Because of those differences, scientists have been cloning stem cells and cancer cells to obtain samples that can be compared effectively and generate reliable results. This is the approach taken by several major research organizations such as the US Food and Drug Administration (FDA). Being able to create cell lines from a single cell is essential for developing new therapies.

The method that scientists currently use is to repeatedly dilute cells in order to maximize the occurrences of a given cell. But that takes several weeks, so it’s a long and costly process. Yann Barrandon, an honorary professor at EPFL and stem-cell expert, was hoping for years that engineers would develop a system for turning this step into a simple formality, making his research easier and providing traceability. Tired of waiting, he suggested the project to two EPFL PhD students – David Bonzon and Georges Muller – who took it on with the help of Professor Philippe Renaud at the Microsystems Laboratory 4. After several years of hard work, Bonzon and Muller were ready to unveil their device; they created SEED Biosciences and, in association with other researchers, just published two articles in SLAS Technology. “Several systems have been introduced over the past few years, but ours – called Dispencell – is the first to tick all the boxes. It’s easy to use, doesn’t affect cell functions, can be sterilized, improves traceability, and more,” says Bonzon, the company’s CTO.

To use the device, scientists pipette 20 µL of a solution with a high cell concentration, drawing in a few hundred cells. They then place the pipette’s tip into the dish where they want to dispense the cells. By pressing a button, they can release individual cells one by one. The system contains an electronic sensor linked to a software program – also developed by SEED Biosciences – that records each cell’s electrical signature. The software is sensitive enough to detect single cells as they pass through the tip. They are then displayed on a computer screen as sharp peaks. The company is now working on a feature that can distinguish damaged cells from healthy ones.

Two electrodes in the pipette’s tip

Part of the device’s secret is that it uses a 50-year-old mechanism called a Coulter counter. With this counter, particles pass between two chambers separated by a tiny hole while an electric current is applied across the hole. In SEED Biosciences’ device, one electrode is located against the pipette’s tip and another is placed in the solution. A thin membrane with a 30 μm hole stretches across the very tip of the pipette and allows the cells to pass through one by one. The device detects and records the cells as they pass through; because the cells are not conductive, they cause changes in the current based on the cells’ size. By measuring the change in current, the software determines the cells’ passage and electrical signature. The pipette tips are designed to be sterilized and replaced so as to avoid contamination.

The device is initially intended for the pharmaceutical industry but also has promising applications in personalized medicine. SEED Biosciences is currently carrying out a funding round to support its market launch.