Diffusion membrane micropump, device, and associated method

Abstract

The present invention is directed to pumps, device, and methods for handling liquids on a microscale. Specifically, a microfluidic pump is described in which liquid in a fluid microchannel may be moved in either direction due to the diffusion of a gas through a diffusion membrane in response to a pressure differential applied through a control microchannel. This pump can provide non-contact, and optionally, bi-directional movement of liquid in microfluidics platforms, as well as bubble-free filling of dead-end microchannels and reservoirs.

Description

BACKGROUND OF THE INVENTION

Microfluidics has become an increasingly versatile platform for a number of applications including for uses with the so-called “lab-on-a-chip.” Microfluidic systems make it possible to integrate multiple fluid handling and analysis tasks into a small structure. This ability yields at least two benefits. First, analyses that would otherwise require extensive laboratory apparatuses may now be done using a small, portable platform that can be made from relatively inexpensive materials. Second, very small samples—in the microliter and nanoliter range—can be subjected to multi-step analysis in a microfluidic chip with minimal sample loss. This can be particularly significant in applications such as forensics, genetic testing, assays, and drug screening.

Given the increasing complexity of the lab-on-a-chip and other microfluidics platforms, it is recognized that the ability to effectively move fluids about within them is an important concern. Effective microfluidic analysis necessitates a high level of control over each fluid plug. Chips can feature intricate networks of fluid microchannels, and certain functions, such as mixing, must be accomplished by sending various fluids into circular or dead-end channels. One advantage of microfluidic platforms is that, due to the small dimensions of the channels, fluid flow therein is almost completely laminar. The result of this characteristic is that fairly predictable movement of fluids can be achieved inside the platform. However, the nature of a microfluidic approach can also present a unique set of challenges. For example, some fluids should be moved at low velocities to avoid premature phase separation or cavitation. The presence of air bubbles in a blind end of a channel can prevent effective filling, leaving unwanted dead air spaces. In view of these and other concerns, a need is recognized for a means of moving fluids within microfluidic channels so as to best benefit from the advantages of such systems.

SUMMARY OF THE INVENTION

Briefly, and in general terms, the invention is directed to a microfluidic pump, comprising a diffusion membrane, a control microchannel, and a fluid microchannel. The control microchannel can comprise an open end and a closed end, wherein the open end is in functional communication with a pressure source configured to produce a pressure change inside the control microchannel, and the closed end is defined at least in part by the diffusion membrane. The fluid microchannel can comprise at least one open end, and configured to contain a volume of liquid, wherein the diffusion membrane is in communication with an interior of the fluid microchannel so that a pressure change produced by the pressure source induces a permeant gas to move through the diffusion membrane, thereby causing the liquid to move in a direction within the fluid microchannel.

In another embodiment, a microfluidic device can comprise one or more microfluidic pumps as described above, one or more wells configured to receive liquid from outside the device to be delivered to the one or more microfluidic pumps, and one or more wells configured to receive liquid from the one or more microfluidic pumps for retrieval from the device.

In another embodiment, a method of moving liquid in a fluid microchannel can comprise multiple steps, including the step of providing a fluid microchannel which includes an open end and a closed end. The fluid microchannel can contain a volume of liquid and a volume of permeant gas at least substantially sealed between the closed end and the volume of liquid, wherein an inner surface of the fluid microchannel proximate the volume of permeant gas is in fluid communication with a diffusion membrane. Another step includes removing at least a portion of the volume of permeant gas out of the fluid microchannel through the diffusion membrane, thereby causing the volume of liquid to move due to negative pressure created by removing the portion of the volume of permeant gas.

BRIEF DESCRIPTION OF THE DRAWINGS

Additional features and advantages of the invention will be apparent from the detailed description which follows, taken in conjunction with the accompanying drawings, which together illustrate, by way of example, features of the invention; and, wherein:

FIG. 1A depicts a representation of a diffusion-based membrane pump utilizing applied positive pressure, where a fluid plug is moved from an enclosed end of a fluid microchannel to a sample well open to atmospheric pressure, and where the control microchannel is separated from the fluid microchannel from the diffusion membrane.

FIG. 1B depicts a representation of a diffusion-based membrane pump utilizing negative pressure (vacuum), where a fluid plug is moved from a sample well into an enclosed end of the fluid microchannel, and where the control microchannel is separated from the fluid microchannel from the diffusion membrane.

FIG. 2 depicts a three-layered device including a fluid microchannel layer, a diffusion membrane, and a control microchannel layer.

Reference will now be made to the exemplary embodiments illustrated, and specific language will be used herein to describe the same. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT(S)

In describing and claiming the present invention, the following terminology will be used in accordance with the definitions set forth below.

The singular forms “a,” “an,” and, “the” include plural referents unless the context clearly dictates otherwise.

The term “microfluidics” refers generally to the use of constructs for handling and analysis of very small volumes of liquid, as a way of miniaturizing biological and chemical laboratory processes. As such, constructs are often referred to as a “lab on a chip.” Microfluidics also refers particularly to such uses involving structures having elements that are smaller than 1 mm in at least one dimension.

The term “plug” refers to a volume of a liquid of interest situated in a channel of a microfluidic device, where the length of the volume of liquid is not interrupted by an empty space longer than half of the total length occupied by the liquid.

The term “functional connection” when used herein refers to a connection between two structures or elements of a structure that allows an intended interaction between them. In the context of microfluidics elements, a functional connection is also referred to providing “communication” between two elements, such that certain substances located in one element may move or be moved into the other element by passing through the functional connection.

The term “gas-permeable” refers to a property of material that permits gaseous substances to diffuse therethrough in response to a chemical potential. The diffusion may occur by a transport mechanism based in the material that moves individual molecules across, or it may occur by groups of molecules passing through pores in the material. A material may be selectively permeable, e.g., allowing certain substances to pass through more readily than others, often due to specificity in the transport mechanism. The term “permeant” or “permeant gas” refers to a gas or fraction thereof to which a gas-permeable diffusion membrane is permeable and that is available to diffuse or has diffused through the membrane.

Ratios, concentrations, amounts, and other numerical data may be presented herein in a range format. It is to be understood that such range format is used merely for convenience and brevity and should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. For example, a length range of about 1 μm to about 20 μm should be interpreted to include not only the explicitly recited lengths of 1 μm to about 20 μm, but also to include individual lengths such as 2 μm, 3 μm, 4 μm, and sub-ranges such as 5 μm to 15 μm, 10 μm to 20 μm, etc.

In general terms, microfluidic technology represents a way of miniaturizing biological and chemical processes so that they may be incorporated into a benchtop or handheld platform. Such a platform may comprise either a monolithic or a layered construct, into which are cut or etched a number of reservoirs or wells for receiving or holding liquids. These wells may be constructed so as to be directly accessible from outside the platform, so that liquids may thereby be introduced into or withdrawn from the wells. Alternatively or in addition to this feature, the chip may include ports configured to accept attachments to various other components, including one that provides or withdraws fluid or gas, or another microfluidic chip. Furthermore, channels may be cut into the chip to facilitate communication of liquids among separate wells.

Microfluidics devices having the above mentioned features often utilize a means for moving a droplet or other volume of liquid therein in a desired direction along the channels. This may serve to empty or fill a particular well or other space with a particular liquid, or to facilitate mixing of two or more fluids. In light of these recognitions, the present invention provides a microfluidic pump that utilizes a non-contact mechanism of impulsion, in which a gas-permeable diffusion membrane mediates the application of pressure differentials between control and fluid microchannels.

In accordance with this, a microfluidic pump can comprise a diffusion membrane, a control microchannel, and a fluid microchannel. The control microchannel can comprise an open end and a closed end, wherein the open end is in functional communication with a pressure source configured to produce a pressure change inside the control microchannel, and the closed end is defined at least in part by the diffusion membrane. The fluid microchannel can comprise at least one open end, and configured to contain a volume of liquid, wherein the diffusion membrane is in communication with an interior of the fluid microchannel so that a pressure change produced by the pressure source induces a permeant gas to move through the diffusion membrane, thereby causing the liquid to move in a direction within the fluid microchannel.

In another embodiment, a microfluidic device can comprise one or more microfluidic pumps as described above, one or more wells configured to receive liquid from outside the device to be delivered to the one or more microfluidic pumps, and one or more wells configured to receive liquid from the one or more microfluidic pumps for retrieval from the device.

In another embodiment, a method of moving liquid in a fluid microchannel can comprise multiple steps, including the step of providing a fluid microchannel which includes an open end and a closed end. The fluid microchannel can contain a volume of liquid and a volume of permeant gas at least substantially sealed between the closed end and the volume of liquid, wherein an inner surface of the fluid microchannel proximate the volume of permeant gas is in fluid communication with a diffusion membrane. Another step includes removing at least a portion of the volume of permeant gas out of the fluid microchannel through the diffusion membrane, thereby causing the volume of liquid to move due to negative pressure created by removing the portion of the volume of permeant gas.

It is noted that discussion of each of these embodiments is provided herein by way of example, and discussion of one embodiment is generally applicable to other embodiments, regardless of the context of the discussion. For example, discussion of the pump or device can be equally applicable to embodiments related to the method, or vice versa.

In accordance with embodiments of the present invention, the pumps, devices, methods, or the like can utilize a diffusion membrane comprising polydimethysiloxane (PDMS) material, or other similar membrane material. Thickness can be from 5 μm to 200 μm, or in some embodiments, from 20 μm to 120 μm. In some embodiments, pumps according to the present invention provide for movement of liquid without requiring the diffusion membrane to touch the liquid.

In further detail, a microfluidic pump can comprise a control microchannel and a fluid microchannel, and a diffusion membrane interposed between them so that a permeant gas can pass from inside one channel into the other by diffusing across the membrane. Preferably the control microchannel has one open end by which an intended permeant gas can be introduced into or withdrawn from the channel. This may be accomplished by connecting a pressure source to the open end of the control microchannel by way of a tube, nozzle, pipe, or other conduit. The control microchannel often also has a closed end that is defined at least in part by one or more diffusion membranes, each situated so as to provide communication between the interior of the control microchannel and the interior of a fluid microchannel. In a particular embodiment, a diffusion membrane may be located at any point along the length of the control microchannel, providing communication with a fluid microchannel that is juxtaposed thereto. In another embodiment, more than one fluid microchannel may be juxtaposed to a particular control microchannel. In such an embodiment, the control microchannel may feature a diffusion membrane at each junction with a fluid microchannel. One implementation of this approach is to use a single diffusion membrane that is large enough to provide communication with more than one fluid microchannel. Alternatively, a separate membrane may be devoted to each fluid microchannel/control microchannel junction.

The fluid microchannel can contain a volume of a liquid that is to be moved. In a particular embodiment, the liquid will be situated so that some space exists between it and the diffusion membrane. In a typical embodiment, a liquid is introduced into a well with which a fluid microchannel communicates. However, a pump according to the present invention can be used to move liquid situated at any point along a fluid microchannel or within a network of such channels. The direction in which the pump moves the liquid will depend on whether the pressure source connected to the control microchannel provides positive pressure or negative pressure.

In an exemplary embodiment which utilizes positive pressure, reference is now made to FIG. 1A. In this system, a pressure source 10 is used to apply positive pressure to the interior of a control microchannel 12 by increasing its output of permeant gas. The permeant gas in the control microchannel, or any component thereof to which the membrane is permeable, will begin to move down the control microchannel and across a diffusion membrane 16. The liquid (positioned at 18a) resting in the closed end 20 of a fluid microchannel 22 is pushed down the fluid microchannel (liquid moving toward 18b) by the permeant gas. The liquid (moving toward and arriving at 18c) may then be retrieved from a sample well 24.

In an exemplary embodiment utilizing negative pressure as depicted in FIG. 1B, a pressure source 26 connected to a control microchannel 28 can be a vacuum source, or any physical or chemical construct configured to draw permeant gas out of the control microchannel. Negative pressure exerted on the control microchannel by the pressure source causes permeant gas within the control microchannel to move toward the pressure source and permeant gas within a fluid microchannel 32 to move toward a diffusion membrane 34. As a result, the liquid (positioned at 36a) resting in a sample well 38 will move in a direction down the fluid microchannel, i.e., toward the diffusion membrane (liquid moving toward 36b and then toward and arriving at 36c). It is preferable, but not necessary, that the diffusion membrane be substantially impermeable to the liquid, so that liquid that reaches the membrane does not pass into the control microchannel. Rather, the liquid will collect in a closed end 40 of the fluid microchannel adjacent to the diffusion membrane. As evidenced by the embodiment depicted in FIG. 1B, the present invention also provides a method of filling a closed end in a fluid microchannel. Such a method provides for bubbles of permeant gas in the closed end or elsewhere in the plug of liquid to be removed via the diffusion membrane, resulting in the closed end being filled with liquid and being substantially free of gas bubbles.

Pumps according to the present invention may utilize sources of either positive pressure or negative pressure to provide unidirectional liquid movement within fluid microchannels in microfluidic platforms. Bidirectional movement within fluid microchannels is also possible when both types of pumps are connected to each fluid microchannel. In alternative embodiments of the present invention, both positive and negative pressure may generated by a single pump to provide bidirectional flow. In one embodiment, a fluid microchannel may interact with two control microchannels, both of which are connected to the same type of pressure source. A plug of liquid situated between the two control microchannels may thereby be moved in either direction by activating one pressure source or the other. In another alternative embodiment, a control microchannel may be branched so that it has two open ends, one connected to a positive pressure source and the other to a negative pressure source. In still another alternative embodiment, a single pressure source capable of dual modes of operation—positive pressure and vacuum—may be utilized. In any of these or other embodiments, bi-directionality of movement can be quite useful in microfluidics applications. For example, the ability to move a plug of liquid back and forth can facilitate precise placement of the liquid at a specific location within the fluid microchannel, which may be desirable to bring a sample in contact with a sensor or in line with a source of electromagnetic energy. Bidirectional movement may also be used for mixing. For example, a liquid sample and a reagent may be brought together in one channel featuring a pump as described above, and then be gently mixed by moving them back and forth in the channel. In addition, by using control microchannels capable of applying both positive pressure and negative pressure, liquid may be steered within a complex network of microfluidic channels. For example, liquid in a well connected to the intersection of a number of fluid microchannels may be directed to any subset of those channels by using individual control microchannels to apply negative pressure to the desired channels while maintaining a positive pressure in the others.

Because the pumps of the present invention utilize permeant gases to move liquids, they provide a non-contact pumping mechanism. That is, unlike other mechanical pumping means such as peristalsis, the liquid to be moved does not need to come into contact with the membrane or the control microchannel. Therefore, fabrication of the diffusion membrane may be dictated by desired qualities other than chemical compatibility with intended sample substances. The membrane can be permeable to any number of gases, including nitrogen, oxygen, and carbon dioxide, as well as vapors from volatile substances that are substantially liquid at standard temperatures and pressures, such as ethanol and toluene. Where the membrane is selectively permeable, the liquid in the fluid microchannel can be more exposed to the molecules for which the membrane is more permeable. Therefore, the permeant gas may be chosen according to a desired effect of the gas on the liquid. For example, gas may be used that substantially comprises a molecule to be dissolved in the liquid. Conversely, the permeant gas may be chosen so as to minimize any effect on the liquid, i.e. a gas substantially comprising molecules having poor solubility in the liquid, or that are chemically inert. Precise handling of liquids and bubble-free dead-end filling within microfluidic platforms can be effectuated by achieving appropriate flow rates. Flow rate within a channel can depend on properties of the liquid, such as viscosity, as well as of properties of the channel itself, such as internal height and width, roughness of the interior surfaces, and/or surface charge density. In accordance with embodiments of the present invention, the properties of the membrane can also be significant, in that flow rate can depend on the rate at which a given permeant gas passes through a given area of membrane. This rate depends, at least in part, upon the permeability of the membrane to the gas in question, the thickness of the membrane, and/or the pressure difference across the membrane. Flow rates generated by the pumps of the present invention can range from very slow (about 1 nl/min) up to about 500 nl/min. In certain embodiments, the average rate of delivery of liquid to another point in the fluid microchannel can be from 1 nl/min to 100 nl/min, or from 1 nl/min to 50 nl/min. In another embodiment, the average rate of delivery of liquid to another point in the fluid microchannel can be from 10 nl/min to 200 nl/min. The pressures generated within the control microchannel to achieve these flows can be from 0 mbar to 900 mbar.

Diffusion membranes for use in the present invention may be made from a number of materials that are amenable to forming a sufficiently thin layer, are permeable to gases, and have sufficient tensile strength to withstand the pressures applied by the pressure source. Possible materials for microfluidics membranes include polyimides, polyamides, polyacrylates, and polysiloxanes. It is desirable that the membrane is made from a material that is selectively permeable to a group of gases including the intended permeant gas. One particular material that can be used for membranes in the present invention is polydimethylsiloxane (PDMS). PDMS is a silicone elastomer that is highly gas-permeable as well as being inexpensive, biocompatible, and amenable to rapid prototyping.

Flux of gases through gas-permeable membranes can be inversely proportional to the thickness of the membranes. The membrane utilized in the present invention should be robust enough to withstand the pressures generated by the pressure source while being thin enough to allow a flux of gas sufficient to move the liquid in the fluid microchannel. Diffusion membranes according to the present invention can have a thickness from 5 μm to 200 μm. According to one embodiment, such membranes can have a thickness from 20 μm to 120 μm. The operative surface area of diffusion membranes in microfluidics pumps can also be limited by the size of the channels with which they communicate. Microfluidics platforms typically include features having a smallest dimension no larger than about 1 mm. Therefore a typical width of a diffusion membrane according to the present invention can be the width of a fluid microchannel, i.e. 1 mm or less. However, such membranes may communicate with a length of a fluid microchannel as appropriate for a specific platform.

The present invention also provides a microfluidic device incorporating one or more microfluidic pumps as described above. Microfluidic devices can be constructed from a number of materials known in the art to be suited for this purpose, including glass, silicone, silicone elastomers, photoresist, hydrogels, and/or thermoplastic. Silicone elastomers, particularly PDMS, is recognized as having a number of properties that are useful in microfluidics. Therefore, in an embodiment of the present invention, the microfluidic device can be made, at least in part, from PDMS. In order to provide increased functionality, such as reusability and the ability to interface with other platforms, such devices may include means for liquids to be introduced from outside the device, as well as means for retrieving liquids from the device for further handling. In a particular embodiment, these means are provided by wells molded into or cut out of the material of the device. In another embodiment, these means may include ports that facilitate connection of a structure holding the liquid with one or more fluid microchannels in the device.

Microfluidics platforms are often fabricated using multilayer soft lithography techniques. Accordingly, fabrication of devices incorporating the membrane-based pumps of the present invention may utilize similar techniques. For example, the fluid microchannels, diffusion membranes, and control microchannels may each occupy different layers. An exemplary embodiment of such a device comprising three layers is depicted in FIG. 2. A fluid microchannel layer 42 is molded from a suitable material and fluid microchannels 44 are etched into its bottom surface 46. Sample wells 48 may then be cored out of the fluid microchannel layer so that each sample well opens onto a fluid microchannel. A control microchannel layer 50 can also be molded from the same material as the fluid microchannel layer, and a control microchannel 52 is etched into its upper surface 54. An access port 56 is cored out of an edge 58 of the control microchannel layer so that it opens onto the control microchannel. Also present is a thin, gas-permeable diffusion layer 60 is fabricated from a suitable gas-permeable material. The respective layers may then be assembled with the diffusion layer on top of the control microchannel layer, and the fluid microchannel layer on top of the diffusion layer, and oriented so that the control microchannel is perpendicular to the fluid microchannels. In the resulting device 62, each junction 64 provides communication between the fluid microchannels and the control microchannel via the diffusion layer.

EXAMPLES

The following examples illustrate embodiments of the invention that are presently known. Thus, these examples should not be considered as limitations of the present invention, but are merely in place to teach how to make the best-known devices and methods of the present invention based upon current experimental data.

Example 1—Fabricating a Microfluidic Device Incorporating Permeable Membrane Micropumps

A microfluidic device was created utilizing multi-layer soft lithography. Devices prepared include a fluid microchannel layer, a thin gas-permeable diffusion membrane layer, and a positive pressure/vacuum control microchannel layer.

For fabricating the layers, PDMS (Sylgard 184 from Dow Corning, Inc.) was prepared at a ratio of 10:1 base to curing agent. The mixture was poured into cast vinyl molds with an adhesive backing (Scotchcal 220 from 3M, Inc.) The molds were patterned using a high-resolution knife plotter (FC5100 A-75 from Graphtec, Inc.) by the Xurography method to yield molds that were 100 μm deep. After cutting the material, it was removed and placed on poly(methyl methacrylate) (PMMA) wafers. Molds were created for a layer having a 1 mm wide control microchannel layer, and a fluid microchannel layer containing channels from 200 μm to 1 mm wide.

After being placed in these molds, the PDMS mixture was partially cured at 65° C. for 45 minutes. Wells and tubing inlets were then cored in the fluid microchannel and control microchannel layers using a 2 mm diameter coring tool. The thin diffusion membrane layer was spun on a PMMA wafer and cured at 65° C. for 45 minutes. The control microchannel layer was placed on top of the thin membrane layer and baked at 65° C. for 30 minutes. Bonding occurred between these two layers so that the membrane layer could be easily peeled from the PMMA wafer. The fluid microchannel layer was then placed on the other side of the membrane layer and baked at 65° C. overnight. The fluid microchannels were filled with Pluronic F108 surfactant (1 wt % in water) and allowed to incubate for 1 hour, in order to enhance liquid movement through the channels.

Example 2—Testing Functionality of Permeable Membrane Micropumps

A vacuum pump is connected to the microfluidic device fabricated in Example 1 through tubing that is pressure fitted into the control microchannel inlet. Water containing colored dye is inserted into the wells only. Vacuum is applied to the control microchannel and the colored water is thereby drawn down the fluid microchannels toward the control microchannel. A positive pressure pump is also used to move the fluid in the opposite direction, thereby providing means for bi-directional fluid flow.

While the forgoing examples are illustrative of the principles of the present invention in one or more particular applications, it will be apparent to those of ordinary skill in the art that numerous modifications in form, usage and details of implementation can be made without the exercise of inventive faculty, and without departing from the principles and concepts of the invention. Accordingly, it is not intended that the invention be limited, except as by the claims set forth below.

Claims

1. A microfluidic pump, comprising:

a) a diffusion membrane;

b) a control microchannel having an open end and a closed end, wherein the open end is in functional communication with a pressure source configured to produce a pressure change inside the control microchannel, and the closed end is defined at least in part by the diffusion membrane; and

b) a fluid microchannel having at least one open end, and configured to contain a volume of liquid, wherein the diffusion membrane is in communication with an interior of the fluid microchannel so that a pressure change produced by the pressure source induces a permeant gas to move through the diffusion membrane, thereby causing the liquid to move in a direction within the fluid microchannel.

2. The microfluidic pump of claim 1, wherein the pressure source is configured to produce a positive pressure change inside the control microchannel sufficient to move the permeant gas from the control microchannel across the diffusion membrane into the fluid microchannel, thereby pushing the liquid away from the diffusion membrane.

3. The microfluidic pump of claim 1, wherein the pressure source is configured to produce a negative pressure change inside the control microchannel sufficient to move permeant gas from the fluid microchannel across the diffusion membrane into the control microchannel, thereby pulling the liquid toward the diffusion membrane.

4. The microfluidic pump of claim 1, wherein the pressure source is also a source of permeant gas.

5. The microfluidic pump of claim 1, wherein the diffusion membrane comprises polydimethylsiloxane.

6. The microfluidic pump of claim 1, wherein the diffusion membrane has a thickness of from 5 μm to 200 μm.

7. The microfluidic pump of claim 6, wherein the diffusion membrane has a thickness of from 20 μm to 120 μm.

8. The microfluidic pump of claim 1, wherein the average rate of delivery of liquid to another point in the fluid microchannel is from 1 nl/min to 500 nl/min.

9. The microfluidic pump of claim 1, wherein the average rate of delivery of liquid to another point in the fluid microchannel is from 10 nl/min to 200 nl/min.

10. The microfluidic pump of claim 1, wherein the liquid is not in physical contact with the diffusion membrane.

11. The microfluidic pump of claim 1, wherein the device is configured for generating bi-directional flow of the volume of liquid.

12. The microfluidic pump of claim 11, wherein the bi-directional flow is generated by providing a vacuum in the fluid microchannel to drive the volume of liquid in a first direction, and providing increased pressure in the fluid microchannel to drive the volume of liquid in a second direction.

13. The microfluidic pump of claim 1, wherein the volume of liquid is moved without a peristaltic pump.

14. A microfluidic device, comprising

a) one or more microfluidic pumps as in claim 1;

b) one or more wells configured to receive liquid from outside the device to be delivered to the one or more microfluidic pumps; and

c) one or more wells configured to receive liquid from the one or more microfluidic pumps for retrieval from the device.

15. A microfluidic device as in claim 14, wherein the device is formed of a material including a member selected from the group consisting of glass, polydimethylsiloxane, photoresist, hydrogel, thermoplastic, and combinations thereof.

16. A method of moving liquid in a fluid microchannel, comprising:

a) providing a fluid microchannel which includes an open end and a closed end, said fluid microchannel containing a volume of liquid and a volume of permeant gas at least substantially sealed between the closed end and the volume of liquid, wherein an inner surface of the fluid microchannel proximate the volume of permeant gas is in fluid communication with a diffusion membrane; and

b) removing at least a portion of the volume of permeant gas out of the fluid microchannel through the diffusion membrane, thereby causing the volume of liquid to move due to negative pressure created by removing the portion of the volume of permeant gas.

17. The method of claim 16, wherein the step of removing the at least a portion of the volume of permeant gas further includes dead end channel filling the fluid microchannel with the volume of liquid such that the closed end of the fluid microchannel is substantially free from bubbles of the permeant gas.

18. The method of claim 16, wherein the diffusion membrane comprises polydimethylsiloxane.

19. The method of claim 16, wherein the diffusion membrane has a thickness of from 5 μm to 200 μm.

20. The method of claim 16, wherein the diffusion membrane has a thickness of from 20 μm to 120 μm.

21. The method of claim 16, wherein the average rate of delivery of liquid to another point in the fluid microchannel is from 1 nl/min to 500 nl/min.

22. The method of claim 16, wherein the average rate of delivery of liquid to another point in the fluid microchannel is from 10 nl/min to 200 nl/min.

23. The method of claim 16, wherein the volume of liquid is moved without a peristaltic pump.