| Modeling of the fluid flow reveals a smooth, non-turbulent flow in the narrow channels, despite the high fluid velocities-a key feature to keep the cells alive through the sorting. |
Massively parallel microfluidics system allows high-speed sorting of life science fluids for various medical, risk abatement, and bioterrorism applications.
Current live cell sorting technology suffers from limitations that prevent these tools from being used in a clinical environment. These limitations include speed, ease-of-use, and the lack of disposability of the fluid-contacting parts. A MEMS (microelectromechanical system)-based cell sorter being developed under a U.S. DARPA (Defense Advanced Research Projects Agency) contract by researchers at Innovative Micro Technology (IMT), Santa Barbara, Calif., looks to solve these problems.Their device entails massively parallel sorting performed in three-dimensional enclosed microfluidic channels integrated onto a single chip. The chip and accompanying tubing are the only parts of the system that contact the fluid or cells and the chip is designed to be disposable.
| Coils wrap around a magnetic alloy to form an array of electromagnetic motors. |
Sorter architecture
The design goal of this system was to allow separation of rare cells from human blood for clinical re-infusion and diagnostic testing. The cell sorter抯 microfluidic channel and valving system were computer-modeled to determine optimal sizes and configurations.The resulting design has fluid being delivered to the chip through a single tube or "pipe," with a manifold for separating the flow into 32 separate micro-channels. Cells (and carrier fluid) flow through these micro-channels that are designed to separate and optimize the position of the cells for analysis.
| Electro-magnetic coils are used to drive the magnetic valve motors used in an ultra-high-speed MEMS cell sorter. |
The mechanics
Before insertion into the cell sorter system, the sample cells are tagged with conventional fluorophore-based technologies, which are activated within each of the micro-channels by a laser. Once a desired cell is detected using a photo-multiplier tube detector, the cell is diverted via downstream individual high-speed valves to a separate channel for collection.Each channel has its own electromagnetic motor-driven valve system. An electromagnetic system was chosen over the conventional electrostatic systems used in MEMS devices to obtain a relatively larger force and a resulting faster valving operation. On-off valve actuation speeds of less than 30 microsecmany times faster than electrostatic deviceswere obtained with this system.
In each of the 32 channels, desired cells are diverted through this valving system to either a common waste container or to a common tank where the accepted cells from all 32 channels are recombined. The resulting system has one pipe in with the total sample, one pipe out with the sorted cells, and a separate waste container for the undesired cells.
Therapeautic markets
Significant progress has been made at IMT toward producing ultra-high-speed cell sorting to generate pure blood stem cells from human blood. While some integration work remains, the researchers have already demonstrated high-speed valves, integrated optics, fluorescent detection, and high-speed microfluidic flow.The applications of this technology are in the high-speed detection and sorting of cells for cancer therapy, amniocentesis replacement, rare cell detection including early disease detection, and protection against radiation and chemical exposure:
• Clinical cell therapy for cancer treatmentA limiting factor in treating cancer is the destructive effects of chemotherapy on a patient抯 immune system. High purity pre-sorting of the patient抯 blood stem cells allows an otherwise-lethal dose of chemotherapy to be used, followed by re-infusion of the patient抯 stem cells to rebuild their immune system. Exposure to radiation or nitrogen chemicals also destroys the human immune system and re-infusion of stem cells can be used to help these victims.
• Amniocentesis replacementFetal cells are found within samples of a mother抯 blood at low levelsabout 1 ppb. These cells can be sorted from a blood sample rather than invasively extracted, eliminating the need for amniocentesis.
• Very rare cell/disease detectionThe high speed of a MEMS-based cell sorter allows for lower detection thresholds on diseases. For example, anthrax detection may be made sooner within a patient, allowing for early detection and treatment.
