Microfluidic Devices for Studying Biomolecular Interactions

These devices can be fabricated rapidly and inexpensively.

Microfluidic devices for monitoring biomolecular interactions have been invented. These devices are basically highly miniaturized liquid-chromatography columns. They are intended to be prototypes of miniature analytical devices of the “laboratory on a chip” type that could be fabricated rapidly and inexpensively and that, because of their small sizes, would yield analytical results from very small amounts of expensive analytes (typically, proteins). Other advantages to be gained by this scaling down of liquid-chromatography columns may include increases in resolution and speed, decreases in the consumption of reagents, and the possibility of performing multiple simultaneous and highly integrated analyses by use of multiple devices of this type, each possibly containing multiple parallel analytical microchannels.

The principle of operation is the same as that of a macroscopic liquid-chromatography column: The column is a channel packed with particles, upon which are immobilized molecules of the protein of interest (or one of the proteins of interest if there are more than one). Starting at a known time, a solution or suspension containing molecules of the protein or other substance of interest is pumped into the channel at its inlet. The liquid emerging from the outlet of the channel is monitored to detect the molecules of the dissolved or suspended substance(s). The time that it takes these molecules to flow from the inlet to the outlet is a measure of the degree of interaction between the immobilized and the dissolved or suspended molecules. Depending on the precise natures of the molecules, this measure can be used for diverse purposes: examples include screening for solution conditions that favor crystallization of proteins, screening for interactions between drugs and proteins, and determining the functions of biomolecules.

The figure presents a schematic exploded view of a basic microfluidic device according to the invention. The device includes a sheet of polydimethylsiloxane (silicone rubber) that contains the channel and that is sealed to a glass microscope slide. In order to make this sheet, one first makes a mold that comprises a flat surface from which protrudes a ridge having the dimensions of the channel. The mold can be fabricated photolithographically on an oxidized silicon substrate. The silicone-rubber sheet is formed by casting the mixture of silicone-rubber ingredients on the mold.

Prior to assembly, a diamond-tipped drill is used to make holes in the microscope slide at the locations assigned to the inlet and outlet ends of the channel. After cleaning and oxidizing in an air plasma cleaner, the silicone-rubber sheet and the microscope slide are pressed together, taking care to align the holes with the ends of the channels. No adhesive is needed; an irreversible seal is formed spontaneously between the glass and the silicone rubber.

Fittings for tubes to carry the liquid are attached to the edges of the holes in the microscope slide. Particles coated with the substance to be immobilized in the column are suspended in a slurry, which is then flushed along the channel. The channel is narrowed at its outlet end by an amount determined by the size of the particles, such that particles that arrive at the outlet become stuck there, preventing themselves and any others from flowing out of the channel (this phenomenon is known in the art as the keystone effect). As a result, the continued flushing with the slurry causes the channel to become packed with the particles.

This work was done by Wilbur W. Wilson and Carlos D. Garcia of Mississippi State University and Charles S. Henry of Colorado State University for Marshall Space Flight Center.

In accordance with Public Law 96-517, the contractor has elected to retain title to this invention. Inquiries concerning rights for its commercial use should be addressed to:

Mississippi State University
Office of Intellectual Property and Technology Licensing
P.O. Box 5282
Mississippi State, MS 39762
Phone: (662) 325-9263

Refer to MFS-31978-1, volume and number of this NASA Tech Briefs issue, and the page number.