The invention is described in detail below with reference to the following figures:
Before describing the invention in detail, it must be noted that, as used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a substrate” may include more than one “substrate”, reference to “a heating element” may include more than one “heating elements”.
In describing and claiming the present invention, the following terminology will be used in accordance with the definitions set out below.
The term “adjacent” means near, next to, or adjoining.
The term “micro fluidic device” refers to any device that is very small. In particular the term means any type of device in the size range of about 10−6 meters The term should be interpreted broadly to include any number of structures and materials that are on a small scale.
The term “substrate” refers to any materials or components capable of being designed with one or more channels. Substrates may comprise one or more materials that are rigid or non-rigid. It is important that the substrate be capable of holding or designing one or more microfluidic channels.
The term “heating element” refers to any system, component or device know or not known in the art that is capable of providing heat. Heating elements may include and not be limited to IR devices, thermistors, coils, thermocouples, RF devices, magnets, and other standard devices known in the art. Heating may be radiative or by conduction or convection.
The term “cooling element” refers to any system, component, or device known or not known in the art that is capable of removing heat or cooling a channel. A number of cooling elements are known in the art. These devices may be convective, conductive and/or may comprise an interior with one or more fluids. For instance, some of the cooling elements may comprise a solution that may be cooled. The solution then cools the surrounding device.
The term “open state” refers to a condition in which a channel in a microfluidic device or system is in a state or condition that will allow solution to flow. This may or may not be in a completely free flowing state. In certain instances this would include a partially flowing state or allowing some flow. In other embodiments this may mean altering or changing the flow or viscosity properties of a solution thermodynamically.
The term “closed state” refers to a condition in which a channel in a microfluidic device or system is in a state or condition that will not allow analyte solution to flow. In certain instances this may mean a partially closed state or slowing a solution to a substantially slow flowing state. In other embodiments this may mean altering or changing the flow or viscosity properties of a solution thermodynamically.
The term “photodefinable refers to any material or polymer that may be defined or constructed through the use of light.
The separation device 2 may comprise any number of devices or systems that may be capable of being coupled to a microfluidic device 3. For instance, any number of separation systems know in the art may be employed. For instance, the separation system may comprise an HPLC device or system, an isoelectric focusing device, a centrifuge or fractionator, an electrophoresis or polyacrylamide gel, etc. Any device or method known in the art for separating and/or isolating molecules for further analysis. In certain instances, the separation device may be integrated or designed directly into or may comprise a portion of the microfluidic device 3.
The substrate 7 may comprise a single substrate. In other embodiments it may comprise a number of different substrates that are associated with each other or which are attached or fastened together. For instance, in
As discussed earlier, microfluidic channel(s) 8 may comprise a variety of shapes, sizes and volumes. These microfluidic channels 8 may also be designed to intersect or connect for mixing various materials and solutions at various stoichiometric ratios. The channels 8 may be designed in different dimensions and shapes. They may be designed in various directions for moving and caring analyte solutions (See
As shown in
It should be noted that the cooling element 10 stays engaged to maintain the channels 8 in a closed state. In the event that one or more solutions need to be mixed, the heating elements 9 and/or 9′ may be engaged to raise the temperature of the channel 8. This causes the valve to open and allow one or more of the solutions to mix. In certain embodiments, cooling element 9 and/or 9′ may be in the form of a separate cooling block 10. The cooling block 10 may be designed with one or more micro-machined surfaces 15 and/or 15′ that may or may not be raised surfaces that more effectively and efficiently provide for transfer of cold from the second substrate 10, and avoid heat transfer elsewhere.
Having described the apparatus of the invention, a description of the method of operations is now in order. Basically an analyte sample is introduced into the separation device 2. The separation device 2 further separates and/or purifies the sample in preparation for introduction into the microfluidic device 3. The sample is sent from the microfluidic device 3 to the detector 5. The detector 5 may then further separate and/or identify or characterize the molecules.
However, before the analtye sample reach the detector 5 it must pass through the microfluidic device 3. As discussed above the analyte is prepared by a separation device 2. This is not a requirement of the invention. In certain embodiments, the analyte sample may be introduced directly into the microfluidic device 3 without any further purification or separation. Ideally, the analyte will be introduced to the microfluidic device 3 by way of one or more microfluidic channels 8. Certain solutions may be sealed or prevented from entering the main microfluidic channel 8 by use of the present valve design. For instance, the cooling element 10 is engaged to close one or more microfluidic channels 8. This is accomplished by cooling the solutions in the channel to such a level that they no longer will allow flow. The present invention does this in a variety of way and maintains the channels in a closed state. In the event that it is desirable to introduce another solution to the analyte or to allow the analyte to flow for further processing, the heating element 9 or 9′ may then be engaged. The heating element 9 and/or 9′ provides heat at a level that sufficiently heats and melts the analyte in the channel 8 that it allows it to flow. The heating element 9 and/or 9′ and/or cooling element 10 can be engaged at various times for mixing and introducing various amounts in stoichiometric ratios into the channels 8. The cooling element 10 may be disposed in the substrate 11 or may be a separate block that is used to contact the substrate 7 and/or polymeric substrate 11 (See