Deformable polymer membranes
Embodiments of the present invention provide microfluidic devices containing deformable polymer membranes. The devices can be fabricated from a single polymeric block. Actuation of the membranes within the device allows the fluid contained within a microfluidic channel to be manipulated. Exemplary microfluidic devices, such as, peristaltic pumps, sample sorters, and mixers are described.
The present application claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Patent Application No. 60/615,525, filed Sep. 30, 2004, the disclosure of which is incorporated herein by reference.
BACKGROUND OF THE INVENTION1. Field of the Invention
Embodiments of the present invention relate generally to microfluidic operations and deformable polymer membranes.
2. Background Information
Microfluidic components for performing a variety of operations are integral parts of micro-total analysis system applications. For example, cell sorters have become a vital component in micro total analysis systems aiming to investigate biological events at the single cell level. However it has not been easy to integrate different microfluidic components together into a single chip. This has been due to the different and sometimes difficult fabrication requirements for each of the microfluidic components. For example, pumping in micro total analysis is generally achieved using external devices such as syringes or peristaltic pumps or using voltages across the channels generating electrokinetic or electroosmotic flow.
Essential processes such as bonding, aligning, clamping and interconnections for realizing a micro total analysis system generally cause significant device failure rates. Making components from the same basic unit and material facilitates the integration of operations and components. For example, polymers such as poly(dimethyl siloxane) (PDMS) can be used to fabricate various components in microfluidic devices. In addition, easy fabrication processes and simplicity of the device greatly help in integration of these components into a single device.
BRIEF DESCRIPTION OF THE FIGURES
Embodiments of the present invention provide deformable polymer membranes as active components of a microfluidic system. The deformable membranes perform functions associated with the manipulation of liquids in a microfluidic channel. Because the polymer membranes are disposed in the same polymer layer as the active microfluidic channel, manufacture of the microfluidic device is simplified. Although deformable membranes have been exemplified using PDMS, the present invention is not so limited as other elasomeric polymers can be used to fabricate membranes. Using a deformable membrane unit such as that shown schematically in
Referring to
In embodiments of the present invention, peristaltic pumping of fluids within a microchannel is effectuated using deformable membranes and operating channels that are disposed in the same polymer layer as the active microfluidic channel. The deformable membrane unit can be actuated, for example, by pressurizing the operating channels with a gas or liquid. Peristaltic pumps were realized by placing multiple deformable membrane units (a membrane unit is a pair of membranes disposed on opposite sides of a microfluidic channel) in series along a microfluidic channel. Referring now to
Several different parameters, including the external regulated pressure, frequency of actuation, microfluidic channel width, membrane thickness, channel height, and gap between air channels, were tested. Typical operating channel width was 100 μm. Flow rates were calculated by measuring the time taken for fluorescent beads to traverse through a 2.7 mm long serpentine channel.
The results acquired from two exemplary designs for deformable membrane unit placement in a peristaltic pump (as shown in
By controlling the various parameters of actuation and dimensions of the components of the basic deformable membrane unit, it is possible to control the flow velocities and rates. In general, channel aspect ratios of about 1:2 to about 1:10 (width to height) and widths of about 10 to about 100 μm have been used in embodiments of the present invention. Additionally, in general, average membrane thicknesses of about 5 to about 50 μm and distances between membranes located on a side of a channel of about 50 to about 200 μm can be used in embodiments of the present invention. The height and the width of the membranes are typically determined by the dimensions of the intersection of the microchannels that form the membranes which in turn are user-defined variables.
Referring now to
In an exemplary design, the deformable membrane units were placed in the branch channels that when actuated would increase the resistance to flow in the respective branch thereby diverting the direction of flow of the sample to the other branch.
Referring now to
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The micro-fluidic channels represent micro-sized fluid passages that may have a cross-sectional dimensions, channel width, channel height, channel diameter, etc. that may be not greater than approximately one millimeter (mm, one-thousandth of a meter, also 1000 μm). In various embodiments the cross-sectional dimension may be not greater than approximately 500 micrometers (μm, one millionth of a meter), 200 μm, 100 μm, 50 μm, or 10 μm. The invention is not limited to any known minimum cross-sectional dimension for the channels. In various embodiments the cross-sectional dimension may be greater than approximately 0.001 μm (1 nm), greater than approximately 0.01 μm (10 nm), or greater than approximately 0.1 μm (100 nm). The optimal dimension of the channel may depend upon the characteristics of the fluids and/or particles to be conveyed therein. An exemplary micro-fluidic channel which may be used for one or more of an inlet, outlet, or focusing channel, may comprise a rectangular channel having a channel width of approximately 100 μm and a channel height of approximately 50 μm. The rectangular shape and specific dimensions are not required. These miniaturized channels are often useful for handling small sized samples and allow many channels to be constructed in a small substrate, although this is not a requirement. There is no known minimum or maximum length for the channels. Commonly the channel lengths are at least several times their width and not more than several centimeters.
PDMS may offer certain advantages such as compatibility with biological materials and chemicals and transparency to facilitate alignment, although the use of PDMS is not required and other materials may optionally be employed for forming the housing containing the membranes and microchannels. Any machinable, etchable, reformable, moldable, stampable, embossable, or castable elastomeric material (a material that is capable of deforming when pressure is applied and returning to its original shape when pressure is removed) may potentially be used. In general, there are a wide variety of formulations for elastomeric polymers, and a choice of materials may be based upon considerations such as elasticity, gas and/or liquid permeability, cost of fabrication, and/or temperature stability. Suitable polymers include among others, polyurethanes, silicones, polybutadiene, polyisobutylene, polyisoprene, elastomeric formulations of polyvinylchloride, polycarbonate, polymethylmethacrylate, polytetrafluoroethylene (Teflon®), and combinations of these materials. It may be appropriate to form focusing devices of polymers because these materials are inexpensive and may be injection molded, hot embossed, and cast.
In general, almost any non-absorbent material capable of presenting a smooth surface can be used to form the substrate. Possible substrates that could be used include glass; silicon; polymers, such as for example, PDMS, polystyrene, and polyethylene; silicon nitride; silicon dioxide; and metals, such as for example, gold, aluminum, and the like. The housing in which the channels and the membranes are formed may be reversibly or irreversibly attached to the substrate. For example, a PDMS housing can be reversibly attached to, for example, a PDMS or a glass surface through van der Waals forces. Additionally, adhesives such as silicone adhesives and epoxies can be used to bond the housing to the substrate. Choice of method of bonding is dependent in part on the materials chosen for the housing and the substrate, the desired user-chosen operating pressure ranges, and functional compatibility with operating fluids chosen for a particular application and can be effectuated according to well-known methods in the art. Additionally, PDMS, for example, can be oxidatively sealed to, for example, PDMS, silicon, polystyrene, polyethylene, silicon nitride, or glass by exposing the surfaces to be bonded to an air plasma and bringing the surfaces into contact within about a minute after oxidation.
The invention is generally not limited to any known process flow. Suitable process flows may comprise an aqueous, organic, or biological solution. The process flow may contain a species of interest. The species of interest may comprise a biological material, such as a cell, organelle, liposome, biological molecule or macromolecule, enzyme, protein, protein derivative, protein fragment, polypeptide, nucleic acid, DNA, RNA, nucleic acid derivative, biological molecule tagged with a particle, fluorescently labeled biological molecule, charged species, or charged protein. Additionally, a process flow may contain reagents for chemical reactions and the products of chemical reactions.
In general, the deformable membranes can be actuated (deflected) pneumatically, hydraulically, piezoelectrically, thermopneumatically, and magnetically. Pneumatic and hydraulic actuation can be accomplished by pumping a gas or liquid, respectively, into an operating channel. Typically, the gas or liquid can be supplied and vented through a valve that is controlled by a valve drive and a computer generating a programmed actuation pattern that is converted into a control signal. Piezoelectric actuation can be accomplished using, for example, the devices shown in
Precursors for poly(dimethyl siloxane), Sylgard A and B were obtained from Dow Corning Inc. 1 and 6 μm YG fluorescent poly(styrene) beads used to visualize flow were obtained from Polysciences Inc. SU-2035 Photoresist was obtained from Microchem Corp.
An actuation system consisting of hardware and software components was constructed for pneumatically controlling the operating channels. Referring to
The valve drives are enclosed in the signal conditioning box (NI SCC2345, National Instruments) having two RJ45 connectors, two sets of banana connectors and four LEDs. Two sets of banana connectors are to provide the external power which then is converted into the pulsing power by valve drives. There are eight valve drives and each set of banana connector is connected to four valve drives so that enough external power is supplied. Two 12 V power supplies are connected to the banana connectors. The role of valve drive is to turn on and off the external power for solenoid valves so that it generates the patterned pulsing power with particular frequencies.
The application for the actuation system was written in C language. In order to increase the response time to maximum, Graphic User Interface (GUI) was not implemented. Actuation patterns for performing synchronized actuation of the different deformable membrane units were implemented in the software depending on the microfluidic operations. Video microscopy was done using a Canon Digital camera ZV20 that captures the video via an S-video port from the Hamamatsu color CCD camera mounted onto an inverted fluorescence microscope.
Designs of the micro fluidic channels to be fabricated were drawn to scale using L-Edit (Tanner Research) and chrome masks were printed using a Micronics laser writer at Stanford nanofabrication facility.
SU-8 2035 photoresist was spun onto 4″ silicon wafers at 2000 rpm for 30 sec. The wafers were then baked at 65° C. for 6 min. and at 95° C. for 20 min. The wafers are then exposed using UV light (365 nm) at a dose of ˜400 mJ/cm2. The exposed wafers were then baked at 65° C. for 1 min and at 95° C. for 5 min. After post-exposure bake, the wafers were immersed in SU-8 developer for ˜10 min. to develop the unexposed regions. The SU-8 photoresist on the wafer was then silanized for 1 hr by placing the wafers in close proximity with a few drops of trimethylchlorosilane in a vacuum desiccator. The silanized photoresist on the wafer was used as the master for subsequent micromolding experiments.
Ten parts by weight of Sylgard A were added to 1 part by weight of Sylgard B, mixed thoroughly and degassed to remove any air bubbles to form the PDMS precursor. PDMS precursor was poured onto the silanized master and then cured at 65° C. for 1 hr. The cured PDMS was peeled off the master and holes were punched for reservoirs. In order to irreversibly seal the PDMS to a glass cover, the PDMS and the glass cover were placed in a plasma cleaner and treated with plasma (100 W) generated from ambient air for 1 min. and brought into conformal contact within 30 sec.
In the examples shown liquids were flowed through microfluidic channels using gravity. Other methods are also possible, including, for example, pumps and syringes.
Claims
1) A microfluidic device comprising
- a housing formed from a unitary section of polymer;
- at least one microfluidic channel formed in the unitary section of polymer;
- at least two operating channels formed in the unitary section of polymer that are each operably connected to the microfluidic channel by a deformable membrane formed in the unitary section of polymer and separating an operating channel from the microfluidic channel wherein the at least two operating channels are located on opposite sides of the microfluidic inlet channel; and
- a substrate to which the housing is attached.
2) The microfluidic device of claim 1 wherein the device comprises at least four operating channels and at least four membranes.
3) The microfluidic device of claim 1 wherein the device comprises six operating channels and six membranes and wherein three of the six membranes are disposed on one side of the microfluidic channel and three of the six membranes are disposed on an opposite side of the microfluidic channel and wherein the edge-to-edge distance between the three membranes on a side of the microfluidic channel is about 100 μm or less.
4) The microfluidic device of claim 3 wherein three operating channels disposed on one side of the microfluidic channel are directly across from the three operating channels on the opposite side of the microfluidic channel.
5) The microfluidic device of claim 3 wherein the three operating channels disposed on one side of the microfluidic channel are staggered relative to the three operating channels on the opposite side of the microfluidic channel.
6) The microfluidic device of claim 1 wherein the polymer is poly(dimethyl siloxane).
7) The microfluidic device of claim 1 also including mechanism to actuate the membranes comprising at least one valve operably coupled to at least one valve drive that is operably coupled to a computer capable of generating an actuation pattern.
8) The microfluidic device of claim 1 wherein the operating channels also comprise a piezoelectric material for actuating the operating channels.
9) A microfluidic device comprising,
- a housing formed from a unitary section of polymer;
- an inlet microfluidic channel formed in the unitary section of polymer having a branched end comprising two microfluidic outlet channels;
- least two microfluidic hydrodynamic focusing channels formed in the unitary section of polymer to convey focusing flows into the inlet microfluidic channel;
- at least two operating channels formed in the unitary section of polymer and operably connected to the microfluidic inlet channel by a deformable membrane that separates an operating channel from the microfluidic inlet channel wherein the at least two operating channels are located on opposite sides of the microfluidic inlet channel; and
- a substrate to which the housing is attached.
10) The microfluidic device of claim 9 also including a UV-vis, fluorescence, or Raman detector positioned to interrogate a hydrodynamically focused fluid flow.
11) The microfluidic device of claim 10 also including mechanism to actuate the membranes comprising a valve that is controlled by a valve drive and a computer generating an actuation signal in response to a signal from the detector operably coupled to the valve drive.
12) The microfluidic device of claim 9 wherein the polymer is poly(dimethyl siloxane).
13) The microfluidic device of claim 9 wherein the operating channels also comprise a piezoelectric material for actuating the operating channels.
14) A microfluidic device comprising,
- a housing formed from a unitary section of polymer;
- an inlet microfluidic channel formed in the unitary section of polymer having a branched end comprising two microfluidic outlet channels;
- at least two microfluidic hydrodynamic focusing channels formed in the unitary section of polymer to convey focusing flows into the inlet microfluidic channel;
- at least four operating channels formed in the unitary section of polymer and operably connected to the microfluidic outlet channels by a deformable membrane that separates an operating channel from the microfluidic outlet channel wherein two pairs of operating channels are located on opposite sides of a microfluidic outlet channel; and
- a substrate to which the housing is attached.
15) The microfluidic device of claim 14 also including a UV-vis, fluorescence, or Raman detector positioned to interrogate a hydrodynamically focused flow.
16) The microfluidic device of claim 15 also including mechanism to actuate the membranes including a valve that is controlled by a valve drive and a computer generating an actuation signal in response to a signal from the detector operably coupled to the valve drive.
17) The microfluidic device of claim 14 wherein the polymer is poly(dimethyl siloxane).
18) The microfluidic device of claim 14 wherein the substrate is selected from the group consisting of poly(dimethyl siloxane), glass, silicon, polystyrene, polyethylene, silicon nitride.
19) A microfluidic device comprising,
- a housing formed from a unitary section of polymer;
- an inlet microfluidic channel formed in the unitary section of polymer having branched end comprising two microfluidic outlet channels;
- at least four operating channels formed in the unitary section of polymer and operably connected to the microfluidic outlet channels by a deformable membrane that separates an operating channel from the microfluidic outlet channel and wherein two pairs of operating channels are located on opposite sides of a microfluidic outlet channel; and
- a substrate to which the housing is attached.
20) The device of claim 19 wherein the two microfluidic outlet channels rejoin to form a single microfluidic outlet channel.
21) The microfluidic device of claim 19 wherein the polymer is poly(dimethyl siloxane).
22) The microfluidic device of claim 19 wherein the substrate is selected from the group consisting of poly(dimethyl siloxane), glass, silicon, polystyrene, polyethylene, silicon nitride.
23) The microfluidic device of claim 19 wherein the operating channels also comprise a piezoelectric material for actuating the operating channels.
24) A microfluidic device comprising,
- a housing formed from a unitary section of polymer;
- two inlet microfluidic channels to convey two solutions that join to form a single inlet microfluidic channel formed in the unitary section of polymer;
- at least four operating channels formed in the unitary section of polymer and operably connected to the single microfluidic inlet channel by a deformable membrane that separates an operating channel from the microfluidic inlet channel and wherein two pairs of operating channels are located on opposite sides of a microfluidic inlet channel;
- a substrate to which the housing is attached.
25) The microfluidic device of claim 24 wherein the two operating channels disposed on one side of the microfluidic channel are directly across from the three operating channels on the opposite side of the microfluidic channel.
26) The microfluidic device of claim 24 wherein the two operating channels disposed on one side of the microfluidic channel are staggered relative to the two operating channels on the opposite side of the microfluidic channel.
27) The microfluidic device of claim 24 wherein the polymer is poly(dimethyl siloxane).
28) A microfluidic device comprising,
- a housing formed from a unitary section of polymer;
- an inlet microfluidic channel formed in the unitary section of polymer to convey a sample fluid;
- a carrier microfluidic channel formed in the unitary section of polymer joined at one end to the inlet microfluidic channel;
- a second inlet microfluidic channel formed in the unitary section of polymer to convey a carrier fluid that is joined to the carrier microfluidic channel at the other end of the carrier microfluidic channel;
- an operating channel formed in the unitary section of polymer operably connected to the inlet microfluidic channel by a deformable membrane that separates the operating channel from the microfluidic inlet channel and wherein the operating channel is located opposite the carrier microfluidic channel; and
- a substrate to which the housing is attached.
29) The microfluidic device of claim 28 wherein the polymer is poly(dimethyl siloxane).
30) The microfluidic device of claim 28 wherein the substrate is selected from the group consisting of poly(dimethyl siloxane), glass, silicon, polystyrene, polyethylene, silicon nitride.
31) The microfluidic device of claim 28 wherein the operating channel also comprises a piezoelectric material for actuating the operating channel.
32) A method of pumping a fluid in a microfluidic channel comprising,
- providing a housing formed from a unitary section of polymer having a microfluidic channel formed within the housing that has two sides and at least two polymer membranes formed in at least one of the sides of the channel and operating channels formed within the housing to allow for the actuation of the membranes;
- flowing a liquid through the microfluidic channel; and
- actuating one or more membranes to cause a change in the flow characteristics of the liquid.
33) The method of claim 32 wherein the actuation of the membrane occurs pneumatically, hydraulically, piezoelectrically, or thermopneumatically.
34) The method of claim 32 wherein the housing is formed from poly(dimethyl siloxane).
Type: Application
Filed: Dec 30, 2004
Publication Date: Apr 6, 2006
Inventor: Narayan Sundararajan (San Francisco, CA)
Application Number: 11/027,469
International Classification: F04B 43/00 (20060101);