Microscopy Methods and Apparatus for Manipulation and/or Detection of Biological Samples and Other Objects
The invention is an integrated circuit(IC)/microfluidic hybrid system that combines the biocompatibility of microfluidic systems with the programmability of IC chips. The hybrid system consists of an IC and a microfluidic system fabricated on top of the IC. Biological cells attached to magnetic beads are suspended inside the microfluidic system where biocompatibility is maintained. The IC contains an array of microcoils which produces spatially-patterned magnetic fields on the surface of the IC. In a given magnetic field pattern, the bead-bound-cells are attracted towards local field peaks and trapped on the surface of the IC. Therefore, by modifying the spatial field pattern and hence by moving the field peak positions, the individual bead-bound-cells can be transported to their desired locations. The modification of the field pattern is done by changing the current distribution in the microcoil array using control electronics. For instance, each microcoil can be connected to its own current source for independent magnetic field control. Magnetic manipulation of bead-bound cells has been widely employed in biology. However, in the conventional approach, a large group of bead-bound-cells are statistically pulled all at once using magnetic fields of low spatial resolution. In contrast, one of the key aspects of this invention is the generation of microscopic magnetic field patterns using the microcoil array, which permits manipulation of many individual cells, moving each cell along a different path. Because the spatial field patterns can be reconfigured by the IC, this hybrid system offers more flexibility in cell manipulation over the conventional microfluidic system. The conventional microfluidic system moves biological samples in a fixed channel network using predetermined valve controls, and hence, different operations require different specific microfluidic systems. In contrast, the hybrid system can perform various and sophisticated cell manipulation operations not by necessarily requiring a change in the microfluidic system structure, but by reconfiguring the spatial pattern of the magnetic fields. In this sense the hybrid system is a programmable microfluidic system. This cell manipulation method is a magnetic counterpart of the electric cell manipulation scheme utilizing dielectrophoresis (DEP). Each approach has its own advantages and disadvantages. For example, while the magnetic method requires more sample preparation efforts (magnetic bead attachment), it is more biocompatible as magnetic fields are transparent to cells. Depending on specific experimental needs, a proper choice should be made between the two technologies, for optimum manipulation operation. Due to low fabrication cost, the hybrid system can be used as a single-use, disposable device. One significant application of the device is to assemble a 2D biological tissue at the microscale. By bringing cells one by one with precise spatial control, the hybrid system can build an artificial tissue in a standardized and repeatable manner with tight demographic quality control measures. The assembled tissue can be used as a model tissue to study communications between different types of cells or to test drug efficacy.
Reference: Yong Liu, Hakho Lee, Robert M. Westervelt, and Donhee Ham,
"IC/microfluidic hybrid system for biology: review,"
(Invited Paper) IEEE BCTM, Oct. 2005.
Patent Status: Pending
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Westervelt, Robert M.
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