Microfluidic devices and methods of use thereof

Abstract

The present invention provides novel microfluidic substrates and methods that are useful for performing biological, chemical and diagnostic assays. The substrates can include a plurality of electrically addressable, channel bearing fluidic modules integrally arranged such that a continuous channel is provided for flow of immiscible fluids.

Description

RELATED APPLICATIONS [0001] This patent application claims priority to, and the benefit of, U.S. Provisional Application Nos. 60 / 799,833 filed on May 11, 2006; 60 / 799,834 filed on May 11, 2006; 60 / 808,614 filed on May 25, 2006; 60 / 815,097 filed on Jun. 19, 2006; 60 / 819,733 filed on Jul. 7, 2006; 60 / 819,734 filed on Jul. 7, 2006; 60 / 841,716 filed on Sep. 1, 2006; 60 / 843,374 filed on Sep. 8, 2006; 60 / 833,151 filed on Jul. 24, 2006; 60 / 834,987 filed on Jul. 31, 2006; 60 / 837,871 filed on Aug. 14, 2006; 60 / 837,695 filed on Aug. 14, 2006; 60 / 843,327 filed on Sep. 8, 2006; 60 / 856,540 filed on Nov. 3, 2006; 60 / 856,440 filed on Nov. 3, 2006; 60 / 874,561 filed on Dec. 12, 2006; 60 / 858,279 filed on Nov. 8, 2006; 60 / 858,278 filed on Nov. 8, 2006; 60 / 874,640 filed on Dec. 12, 2006; 60 / 860,665 filed on Nov. 22, 2006; 60 / 873,766 filed on Dec. 8, 2006; 60 / 876,209 filed on Dec. 20, 2006; 60 / 899,258 filed on Feb. 2, 2007; 60 / 903,153 filed on Feb. 23, 2007; 60 / 904,293 filed on Feb. 28, 2007; 60 / 920,337...

AI Technical Summary

Benefits of technology

The present invention provides a microfluidic substrate with individual fluid handling modules that can be combined into fluid processing systems to perform multi-step processing of isolated components. The substrate includes at least two inlet channels and one main channel, which allows for the formation of droplets or nanoreactors of similar sizes. The droplets can be paired and coalesced as they pass through an electric field, resulting in a droplet or nanoreactor with a predetermined size. The substrate can also include a means for storing the sample fluid and a means for introducing the sample fluid to the inlet channel. The invention provides various methods for forming a droplet emulsion library, including methods for introducing the sample fluid and immiscible phase fluid, as well as methods for separating droplets of similar sizes. The technical effects of the invention include improved biological, chemical, and diagnostic applications, faster processing, and lower costs.

Problems solved by technology

However, virtually all microfluidic devices are based on flows of streams of fluids; this sets a limit on the smallest volume of reagent that can effectively be used because of the contaminating effects of diffusion and surface adsorption.

As the dimensions of small volumes shrink, diffusion becomes the dominant mechanism for mixing leading to dispersion of reactants; moreover, surface adsorption of reactants, while small, can be highly detrimental when the concentrations are low and volumes are small.

As a result current microfluidic technologies cannot be reliably used for applications involving minute quantities of reagent; for example, bioassays on single cells or library searches involving single beads are not easily performed.

However, essentially all enabling technology for microfluidic systems developed thus far has focused on single phase fluid flow and there are few equivalent active means to manipulate droplets requiring the development of droplet handling technology.

For example, as the scale of these reactors shrinks, contamination effects due to surface adsorption and diffusion limit the smallest quantities that can be used.

Although utility of electrophoretic control of droplets is great, it does have significant limitations.

First, the charging of droplets is only effectively accomplished at the nozzle.

Second, the discharge path required to eliminate screening effects also discharges the droplets.

Third, finite conductivity of the carrier fluid, however small, will eventually discharge the droplets.

Therefore, once the droplet is formed, there is essentially only one opportunity to perform any pondermotive function which relies on the droplet's charge density (such as coalescing oppositely charged droplets through their mutual Coulombic attraction, or electrophoretically sorting a droplet), and that function can only be performed as long as sufficient charge has not leaked off of the droplet.

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