SAN FRANCISCO A group of Italian researchers is closer to moving medical research and diagnosis into the lower cost realm of lab-on-a-chip by proposing a CMOS-based device for individual cell manipulation, detection and analysis.
Using this week's (Feb. 9) ISSCC conference as a platform, Silicon Biosystems (Bologna, Italy), in conjunction with the University of Bologna, proposed a biochip that it says could reduce the time period for common experiments from several days to just hours and find broad application in medical diagnostics, drug discovery and basic biomedical research.
The main features of the approach include the possibility to handle parallel detection of more than 10,000 cells; the chip's software programmable flexibility, and the possibility of putting embedded sensors into the silicon, which can detect the presence of particles.
Instead of using the more common approaches of manipulating cells, the chip employs dielectrophoresis (DEP), or the practice of moving uncharged particles as cells usually are via polarization induced by non-uniform electrical fields.
The researchers capture cells in "DEP cages" in a two-dimensional field, allowing the lateral movement of individual cells across a silicon substrate. Prior to this, 3-D grids were used to trap and move cells, making them incompatible with a planar CMOS environment; or a one-dimensional, PCB scheme was used that could only manage particle clusters, not individual cells.
Avoiding the clogging
"This is a channel-less architecture, as opposed to mainstream lab-on-a-chip, which relies on fluid flow and micro-machining channels, which are prone to clogging," said Nicolo Manaresi, a Silicon Biosystems researcher who presented the paper Tuesday. "It is also contact-less movement because the cells are levitated inside the micro-chamber (DEP cages) so this is less prone to the cells sticking to the device surface."
In practice, medical researchers trying to quickly ferret out particular cells could work with thousands of suspect cells at a time, using a simple methodology to winnow out the innocent. By coating a microbead with antibodies for a known cell receptor, researchers could search for suspect cells by adjusting the voltage levels across the silicon substrate to steer the bead into other cells. After such a mating, if the bead and cell resist being pulled apart, it will verify that the cells coating the bead match the receptors on the target cell's surface, thus identifying the cell, the authors said. This method could be applied widely in drug screening.
The chip has been prototyped in a 0.35-micron, 2 polysilicon, 3 metal-layer CMOS process.