Single cell treatment

A tiny fluid-filled channel on a microchip that allows single cells to be treated and analysed could lead to advances in drug and gene screening and early disease diagnosis.

The tool breaks down cell membranes to allow drug and gene delivery and permits examination of intracellular materials by establishing an electrical current across a microscale channel, said Chang Lu, a Purdue University biological engineer. The Purdue system is different from current techniques that use electricity for drug delivery and cell analysis. The new technique handles one cell at a time and uses a common DC power supply rather than a costly pulse generator.

"Normally when you do testing, you need a lot of cells, and the properties that you record are the average of that cell population," Lu said. "If you carry out the test based on single cells, you have access to a more detailed picture of the cell population and can pinpoint abnormalities more quickly and exactly."

The size of the channel, while small enough to accommodate only one cell at its narrowest diameter, varies in width so that the electric field intensity differs depending on the cell's location in the device, Lu said. The flow rate controls how much time the cell spends in the high electrical field, where a process called electroporation occurs. Controlling the length of time in the high electrical field without turning the voltage on and off helps maintain the cell's viability.

Electroporation, which use electricity to treat cells, opens pores in the cell's outer membrane. This allows materials outside the cell that ordinarily couldn't penetrate the membrane to move through it.

Lu's research team's findings on the development and use of the new device are published online by the journal Analytical Chemistry, a publication of the American Chemical Society.

The Purdue Research Foundation has filed a provisional patent on Lu's technology, and the Purdue Office of Technology Commercialisation is working on licensing the device.

Buffer

The device, called a microfluidic channel, has a liquid buffer moving cells through the channel.

"This device is extremely simple and can be made very cheaply," Lu said. "You only need a single microfluidic channel to achieve this electroporation process, and potentially we can run multiple devices in parallel on a chip. This is very important for efficient, successful screening of drugs and genes."

In this study, the researchers also demonstrated that they could permanently disrupt the membrane so that a cell would release intracellular materials, making it possible for scientists to analyse the inner materials of a single cell.

"This is important for rare cell detection," Lu said. "If you have a very low number of a certain type of cell that is a precursor for a disease, such as some form of cancer, those cells may be buried in the average cell population data of a bulk cell test."

The Purdue Center for Food Safety Engineering currently is funding further research on the device for use in bacteria detection to protect against natural or purposeful introduction of contaminants into the food supply.

The researchers used Chinese hamster ovary cells inserted into the channel equipped with electrodes. A syringe pump continuously transported the liquid and the cells into the channel where they passed through the electrical field.

The electroporation microfluidic device has the potential to screen for many diseases and for determining the basic functions of genes, Lu said.

"Because the device is so small, eventually we'll be able to screen hundreds of genes or drugs at a time with a number of the channels integrated on the same chip," he said.