Device and method for pressure-driven plug transport and reaction

Abstract

The present invention provides microfabricated substrates and methods of conducting reactions within these substrates. The reactions occur in plugs transported in the flow of a carrier-fluid.

Description

[0001]This application is a continuation of application Ser. No. 10 / 765,718, filed Jan. 26, 2004, which is a continuation-in-part of application Ser. No. 10 / 434,970, filed May 9, 2003, which claims the benefit of U.S. Provisional Application No. 60 / 394,544, filed Jul. 8, 2002, and U.S. Provisional Application No. 60 / 379,927, filed May 9, 2002.BACKGROUND[0002]Nonlinear dynamics, in conjunction with microfluidics, play a central role in the design of the devices and the methods according to the invention. Microfluidics deals with the transport of fluids through networks of channels, typically having micrometer dimensions. Microfluidic systems (sometimes called labs-on-a-chip) find applications in microscale chemical and biological analysis (micro-total-analysis systems). The main advantages of microfluidic systems are high speed and low consumption of reagents. They are thus very promising for medical diagnostics and high-throughput screening. Highly parallel arrays of microfluidic sy...

AI Technical Summary

Benefits of technology

[0011]When plugs are formed from more than one plug-fluid, the fluids are rapidly mixed. Mixing inside plugs is further enhanced when the channels are not straight (i.e., when chaotic flows are generated). Aperiodic channel designs are preferred to induce rapid mixing within plugs. In other cases, mixing can be slowed down or controlled such as by using winding channels, varying the fluid viscosities, varying the plug-fluid composition, and twirling, which can also be controlled.

[0017]Crystallization devices can further include capillary tubing used to collect the plugs, to allow for direct detection of crystallization and to eliminate evaporation of solutions during crystallization.

Problems solved by technology

A main disadvantage of EOF is that it is generated by the motion of the double layer at the charged surfaces of the channel walls.

However, this can be a serious limitation in applications that involve proteins that are often charged and tend to adsorb on charged surfaces.

In addition, high voltages are often undesirable, or sources of high voltages such as portable analyzers may not be available.

The main disadvantage of pressure-driven flows is that they normally have a parabolic flow profile instead of the flat profile of EOF.

Overlap of these tails usually leads to cross-contamination of samples in different plugs.

On the other hand, interleaving samples with long buffer plugs, or washing the system with buffer between samples, reduces the throughput of the system.

In contrast, dispersion in pressure-driven flow typically creates a broad range of residence times for a plug traveling in such flows, and this diminishes time control.

So far, microfluidic devices have not be able to compete with stopped-flow type instruments because EOF is usually very slow (although with less dispersion) while pressure-driven flows suffer from dispersion.

In addition, mixing in microfluidic systems is often slow regardless of the method used to drive the fluid because flow is laminar in these systems (as opposed to turbulent in larger systems).

Mixing in laminar flows relies on diffusion and is especially slow for larger molecules such as DNA and proteins.

In addition, particulates present handling difficulty in microfluidic systems.

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