The technical field is microfluidic devices and, in particular, electrostatic sealing devices adapted to microfluidic structures.
Microfluidic structures are commonly used in analytical devices. With the rapid development of affinity surface array techniques in recently years, there is a growing need to combine the use of microfluidic structure with affinity arrays. Intricate microfluidic systems can now be inexpensively mass-produced using tools developed by the semiconductor industry to miniaturize electronics.
Microfluidic devices are usually constructed in a multi-layer laminated structure where each layer has channels and structures fabricated from a laminate material to form microscale voids or channels where fluids flow. A microscale channel is generally defined as a fluid passage that has at least one internal cross-sectional dimension that is less than 500 μm and is typically between about 0.1 μm and about 500 μm.
The surface structure on each layer is usually manufactured through a patterning process. The classical patterning techniques used in microtechnology are photo- and electron beam lithography. Patterned layers are then bonded or sealed to each other to form the microfluidic structure. For example, U.S. Pat. No. 5,443,890 describes a sealing device in a microfluidic channel assembly having first and second flat surface members which, when pressed against each other, define at least part of a microfluidic channel system between them.
Alternatively, a microfluidic structure may be produced using traditional plastic/ceramic replication techniques such as injection molding, casting, and hot embossing. In addition, removable microfluidic components can be employed to deliver samples or reagents to specific areas of a substrate. U.S. Pat. Nos. 6,089, 853 and 6,326,058 describe patterning devices that have patterning cavities located on their surfaces. The devices can be attached to the surface of a substrate, and the substrate can be patterned by filling the patterning cavities with a patterning fluid.
U.S. Patent Application Publication Nos. 20030032046 and 20030047451 describe peelable and resealable patterning devices for biochemical assays. These peelable and resealable patterning devices make use of self-sealing members, which can be applied to the surface of a substrate and then removed to yield a flat surface that facilitates the performance of detection processes.
In all of the above-described cases, the patterning device must be pressed against the substrate by an externally-applied mechanical force to generate a seal between the patterning device and the substrate. Therefore, additional components, such as fasteners, are required to create the mechanical force necessary to generate the seal between the patterning device and the substrate. In the case of peelable and resealable patterning devices, the patterning devices need to be removed with mechanical force and then reassembled during the resealing process. This process of removal and resealing often damages the patterning devices or the patterned surfaces on the substrate.
Thus, a need exists for a patterning device that can be assembled and dissembled easily and quickly.
A microfluidic structure having an electrostatic sealing device is disclosed. The electrostatic sealing device includes a first electrode and a second electrode opposite the first electrode. At least one of the electrodes contains an elastic layer facing the other electrode. The second electrode is capable of moving toward the first electrode and forming a seal with the first electrode in response to a voltage difference between the two electrodes.
Also disclosed is a microfluidic structure having an electrostatic sealing device in a microchannel. The electrostatic sealing device includes one or more pairs of electrodes disposed along the length of the microchannel. Each pair of electrodes contains a first electrode and a second electrode opposite to the first electrode. In each pair of electrodes, at least one of the electrodes is covered by an elastic layer, and the second electrode is capable of moving toward the first electrode and forming a seal with the first electrode in response to a voltage difference between the two electrodes.
Also disclosed is a method for forming a seal between two components of a microfluidic structure. A first component having a first electrode and a second component comprising a second electrode are provided. At least one of the electrodes has an external elastic layer. The first component is disposed opposite the second component with the electrodes opposed. A voltage difference is applied between the electrodes to form a seal between the electrodes.
The electrostatic sealing device eliminates the need for mechanical components that are traditionally used to apply a mechanical force between two components of a microfluidic structure and thus reduces complexity of the microfluidic structure and possible interference with optical interrogation of the microfluidic structure. Moreover, the seal can be established or removed easily and quickly by turning on or off a voltage.
The detailed description will refer to the following drawings, in which like numerals refer to like elements, and in which:
An embodiment of an electrostatic sealing device 100 in a pre-seal condition is shown in
A voltage applied between the electrode 102 and the electrode 104 establishes an electric field between the electrodes. The electric field generates an electrostatic force f internal to the electrostatic sealing device 100 that pulls the electrodes 102 and 104 towards and into contact with each other.
As shown in
f=V2dC/2dz, (1)
with C=ε0A/(z+b0 ε0/ε) (2)
where C is the capacitance between the electrodes 102 and 104, and A is the surface area of the electrodes 102 and 104 (if electrodes 102 and 104 have different sizes, A is the surface area of the smaller electrode).
Incorporating equation (2) into equation (1) and differentiating C with respect to z lead to the expression
f=−V2 ε0A/2(z+b0 ε0/ε)2 (3)
The negative value of f reflects the fact that charges of one polarity on the electrode 102 are attracted toward charges of opposite polarity on the electrode 104.
p=f/A=−εV2/2b2 (4)
According to equation (4), the electrostatic pressure p is proportional to the square of the voltage applied between the electrodes 102 and 104, and is inversely proportional to the square of the thickness b of the elastic layers 106. Table 1 lists the electrostatic pressures p generated for different thicknesses of the elastic layers, assuming that the dielectric constant ε of the material of the elastic layers 106 is twice that of air (εo=8.854×10−12 F/m) for field strengths in the 100-400 mV/μm range.
In the embodiment shown in
Since the electrostatic pressure p generated under the conditions listed in Table 1 is sufficient to create a tight seal between two elastic layers 106 (when both electrodes are covered with elastic layers), between a single elastic layer and the surface of an electrode (when only one electrode is covered with an elastic layer), or between a single elastic layer and a substrate of a material such as glass, plastic or metal (when one electrode is embedded in the substrate), the electrostatic sealing device 100 can form a seal without the application of an external mechanical force. The electrostatic sealing device 100 is ideal for applications that require multiple positioning of microfluidic structures against a substrate, because the seal can be established simply by applying a voltage between the electrode 102 and the electrode 104, and can be removed by removing the voltage from, or by grounding, the electrode 102. Moreover, precise alignment between the electrodes is not necessary in the pre-seal condition. The electrodes tend to align with each other automatically due to the electrostatic attraction between them when a voltage is applied.
In this embodiment, only the electrode 104 is covered with the elastic layer 106. The elastic layer 106 will insulate the major surface of the electrode 102 from liquid located in the microfluidic channel 114 that exists after the formation of a seal between the electrode 102 and the electrode 104. To prevent the fluid in microchannel 114 from providing a conductive path from the sides of the electrode 104 to ground, the electrode 102 may be covered with a thin layer of insulating material or with an elastic layer 106 (not shown in
The removable structure 108 is attached to the substrate 110 by aligning the electrode 102 with the electrode 104 and applying a voltage between the electrode 102 and the electrode 104. The electrostatic force between the electrodes will pull the electrode 102 toward the elastic layer covering the surface of the electrode 104. Contact between the electrode 102 and the elastic layer 106 on the electrode 104 forms a seal between the removable structure 108 and the substrate 110.
The attachment of the removable structure 108 and the substrate 110 to form the microfluidic structure 200 closes the open section of the microfluidic channel 114 and allows the delivery of reagents, buffers, analytes, etc., as well as the performance of other procedures on the affinity surface 112 of the substrate 110.
In the above-described embodiments, the substrate 110 and removable patterning structure 108 may be fabricated using any organic material, inorganic materials or combination thereof that meets the thermal, mechanical, chemical and electrical insulation requirements of a particular application. Examples of the organic materials include, but are not limited to, polystyrene, polypropylene, polyimide, cyclic olefin copolymer (COC), and polyetheretherketone (PEEK). Examples of the inorganic materials include, but are not limited to, glass, ceramics, oxides, crystalline materials, and metals.
The electrodes 102 and 104 are typically composed of one or more thin layers of a conducting material. The thickness of the electrodes is typically in the range of 20 nm-500 μm, and more typically in the range of 100 nm-5 μm. In one embodiment, the electrodes 102 and 104 are composed of one or more layers each of metal such as gold, silver, platinum, palladium, copper, aluminum or an alloy comprising one or more of such metals. In another embodiment, the electrodes 102 and 104 comprise a layer of indium tin oxide (ITO). The electrodes 102 and 104 can also comprise one or more layers of respective elastic conducting materials or elastic conducting-polymer materials, such as polyaniline and polypyrrole. In an embodiment, one or both of the removable structure 108 and the substrate 110 is made of a conducting material, such as a conducting polymer, doped silicon, or metal. In this embodiment, the entire removable structure 108 or the substrate 110 serves as the electrode 102 or 104, respectively.
The geometry of the electrodes 102 and 104 is typically optimized to provide an adequate sealing force for a given distribution of the internal channel pressure. The electrode geometry may also be optimized to provide an automatic alignment between the substrate 110 and the removable structure 108 in directions parallel to the plane of the major surface of the substrate 110.
The material of the elastic layer 106 can be any suitable elastic insulating material. The material of the elastic layer 106 could advantageously have a high arcing resistance and a high dielectric constant, be chemically compatible with the application, and be hydrophobic, although these properties may not be advantageous in all applications. Examples of the material of the elastic layer 106 include, but are not limited to, rubber, thermoplastic rubber, silicone rubber, fluoroelastomer, acrylic, COC, urethanes, polymethylmethacrylate (PMMA), polycarbonate, polytetrafluoroethylene, polyvinylchloride (PVC), polydimethylsiloxane (PDMS), polysulfone, siloxanes, or polyamides. The selection of the material will vary according to the microfluidic device and the assay. The material of the elastic layer 106 may be spin-coated or stamped on the substrate surface, on top of the electrodes, or on both.
In embodiments of the microfluidic device, the components thereof may be transparent, reflecting, or opaque depending on the optical requirements of the application.
A voltage applied between the elastic membrane electrode 103 and the channel electrode 105 establishes an electric field that pulls the elastic membrane electrode 103 towards the channel electrode 105 in the direction shown by arrow C. Because the microchannel 304 has a U- or V-shaped cross-section area, the distance between the membrane electrode 103 and the channel electrode 105 is a maximum at the center of the microchannel 304 and becomes smaller towards the edges of the microchannel 304. Accordingly, the electrostatic pressure p is greatest at the edges of the microchannel 304, since the electrostatic pressure p is inversely proportional to the distance between the electrodes 103 and 105 (see equation (2) above).
As shown in
The above-described “zipper” effect as the elastic membrane electrode 103 and the channel electrode 105 come into contact is opposed by the elasticity of the elastic membrane electrode 103 and the elastic layer 106, as well as by the pressure exerted by the fluid in the microchannel 304. The applied voltage needed to initiate the “zipper” effect is reduced by reducing the gap between the elastic membrane electrode 103 and the channel electrode 105 at the edges of the microchannel 304. The gap can be reduced by structuring the U- or V-shaped microchannel 304 to form a small contact angle a (see
The electrostatic sealing device 310 described above can be used as a shut-off valve, which has only an on state or an off state, or as a regulating valve, which additionally has partially on states. By establishing an appropriate voltage between the elastic membrane electrode 103 and the channel electrode 105, the electrodes 103 and 105 may partially or fully seal the microchannel 304 and thus regulate fluid flow in the microchannel 304. In the electrostatic sealing device 310, the one of the elastic membrane electrode 103 and the channel electrode 105 that is at the higher voltage when a voltage is applied between the electrodes is coated with an elastic layer or a layer of another insulating material to prevent the fluid in the microchannel 304 from providing a leakage path from the higher voltage electrode to ground.
In an embodiment, the inlets of the microchannels 320 and 322 are connected to a common microchannel (not shown). In such embodiment, the channel electrode 105 to which the voltage is applied selectively causes the microfluidic device to route fluid flowing in the common microchannel through the microchannel 320 or through the microchannel 322. When voltage is applied to neither of the channel electrodes, the fluid flows through both of the microchannels.
An electrostatic sealing device in accordance with the invention may also be structured as pump for a microfluidic structure.
Pumping efficiency is maximized by additionally applying the voltage to the next electrode segment pair in the sequence before the voltage is removed from the previous electrode segment pair in the sequence. For example, the voltage is additionally applied to the electrode segment pair 103B and 105B before the voltage is removed from electrode segment pair 103A and 105A. The voltage is removed from electrode segment pair 103A and 105A after the time required for the voltage to fully establish the electrostatic seal between the electrode segment pair 103B and 105B. After the voltage has been applied to the electrode segment pair 103D and 105D, the applying sequence repeats with the application of the voltage to the electrode segment pair 103A and 105A. Alternatively, the voltage can be cumulatively applied to the electrode segment pairs in the sequence 103A and 105A through 103D and 105D.
In an alternative embodiment of the pump provided by the electrostatic sealing device 316, only one of the elastic membrane electrode and the channel electrode is composed of electrode segments disposed along the length of the microchannel 302. For example, a channel electrode common to all the electrode segments 103A-103D is a provided by a continuous electrode coating located on the inner surface of the microchannel channel 302. The elastic membrane electrode remains composed of electrode segments 103A-103D as shown in
Embodiments of the pump provided by the electrostatic sealing device 316 may be used to control fluid movement within the microfluidic device.
In embodiments of the electrostatic sealing device 310 described above with reference to
Many other configurations of the microfluidic device and electrostatic sealing device in accordance with the invention are possible. Depending on the application, the electrostatic sealing device can be used as a valve, a pump, a flow regulator, or a combination thereof. The microfluidic structures 200, 300, 400, 500 and 600 disclosed herein can be used in a variety of applications. Examples include, but are not limited to, detection of binding events such as cell-membrane, cell-cell, cell-substrate/receptor, antibody-antigen, hormone-receptor, small molecule-protein, polynucleotide-polynucleotide, and protein-polynucleotide binding events; detection of chemical modifications such as isomerization, oxidation, and reduction; and detection of biochemical reactions such as enzymatic modification (e.g., cleavage by proteases, phosphotases, lipases, endonucleases, exonucleases, and/or transferases). Accordingly, the microfluidic structures disclosed herein may be used to perform a variety of assays that include, but are not limited to, determination of enzymatic inhibition by a collection of compounds in solution; determination of substrates for an enzyme (fishing/selectivity), identifying binding partners for immobilized biomolecules (such as peptides, proteins, nucleic acids, antibodies, enzymes, glycoproteins, proteoglycans, and other biological materials, as well as chemical substances), identifying inhibitors of protein-protein, protein-small molecule or protein-receptor binding, determination of the activity of a collection of enzymes (in one or more than one well), and generating selectivity indices for inhibitors of enzymes or other biologically active molecules.
Although preferred embodiments and their advantages have been described in detail, various changes, substitutions and alterations can be made herein without departing from the scope of the devices and methods as defined by the appended claims and their equivalents.
Number | Date | Country | |
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Parent | 10701502 | Nov 2003 | US |
Child | 11318994 | Dec 2005 | US |