WO2022177559A1

WO2022177559A1 - Microfluidic detection devices

Info

Publication number: WO2022177559A1
Application number: PCT/US2021/018418
Authority: WO
Inventors: Viktor Shkolnikov; Keith Moore; Steven Barcelo
Original assignee: Hewlett-Packard Development Company, L.P.
Priority date: 2021-02-17
Filing date: 2021-02-17
Publication date: 2022-08-25

Abstract

In accordance with the examples of the present disclosure, a microfluidic detection device is presented. The microfluidic detection device can include a microfluidic chamber, a first electrode, a second electrode, and a heating element. The first electrode and the second electrode can be operable to generate an electric field along a separation region therebetween when a conductive fluid is within the microfluidic chamber at the separation region. The heating element can be positioned within the separation region to thermally couple with and heat the conductive fluid when the conductive fluid is present in the separation region.

Description

MICROFLUIDIC DETECTION DEVICES

BACKGROUND

[0001] In biomedical, chemical, and environmental testing exploiting a component of interest from a sample can be useful. Analysis or amplification of the component of interest can be used in a variety of assays. As the quantity of available assays increases, so does the demand for different processes and more processing of components of interest from samples. Fluidic devices can be used for these applications, among others. In some examples, fluidic devices can be used to prepare and process samples.

BRIEF DESCRIPTION OF THE DRAWINGS

[0002] FIG. 1 graphically illustrates an example microfluidic detection device in accordance with the present disclosure;

[0003] FIG. 2 graphically illustrates an example microfluidic detection device in accordance with the present disclosure;

[0004] FIG. 3 graphically illustrates an example microfluidic detection system in accordance with the present disclosure; and

[0005] FIG. 4 is a flow diagram of an example method of rotating microparticles during a chemical reaction in accordance with the present disclosure. DETAILED DESCRIPTION

[0006] The present disclosure describes microfluidic devices, microfluidic detection systems, and methods of rotating microparticles during a chemical reaction. During a chemical reaction a sample may be combined with reactants. Microfluidic devices can be used in reactions involving sequencing genes, diagnosing viruses, identifying cancers, and the like. The microfluidic devices, systems, and methods herein can be used to rotate microparticles during a chemical reaction.

[0007] In accordance with the examples of the present disclosure a microfluidic detection device is presented. The microfluidic detection device can include a microfluidic chamber, a first electrode, a second electrode, and a heating element. The first electrode and the second electrode can be operable to generate an electric field along a separation region therebetween, when a conductive fluid is within the microfluidic chamber at the separation region. The heating element can be positioned within the separation region to thermally couple with and heat the conductive fluid when the conductive fluid is present in the separation region. In an example, the separation region can be partially defined by a distance between the first electrode and the second electrode of from about 10 pm to about 1 cm. In another example, the first electrode and the second electrode can be transparent to fluorescent emission. In yet another example, the electrodes can be positioned to act on surface-activated microparticles carried by a conductive fluid and positioned within the separation region to provide electro-kinetic rotation, Bom-Lertes rotation, or Quincke rotation. In a further example, the heating element or portion thereof can be positioned beneath the separation region and can be dimensionally as large or larger in surface area as compared to a linear distance between the first electrode and the second electrode.

[0008] In another example a microfluidic detection system is presented. The system can include a microfluidic detection device and microparticles. The microfluidic detection device can include a microfluidic chamber, a first electrode, a second electrode, and a heating element. The first electrode and the second electrode can be used to generate an electric field along a separation region therebetween when a conductive fluid is carried within the microfluidic chamber. The heating element can be positioned beneath the separation region to thermally couple with and heat the conductive fluid when the conductive fluid is present in the separation region. The microparticles can be surface-activated to react with or bind to a chemical component carried by or to be carried by the conductive fluid when present. In an example, the microparticles can have an average core particle size ranging from about 1 pm to about 10 pm. In another example, the system can further include the conductive fluid and the conductive fluid can further operate as a heat sink. In yet another example, a ratio of a surface area of the first electrode and the second electrode at surfaces that interface with the conductive fluid to an exterior surface area of a smallest particle of the microparticles can range from about 2:1 to about 5:1. In a further example, the system can further include a luminescence detection device coupled to the microfluidic detection device. The luminescence detection device can be selected from a single-color illumination and detection imaging system, a multi-color illumination and detection imaging system, an electrochemical detection system, an optical photodiode, or a combination thereof. In one example, the microparticles can be magnetic and the system can further include a magnetic field generator positioned adjacent to the heating element. In another example, the system can further include a hardware controller for controlling operation of the first electrode, the second electrode, the heating element, or a combination thereof.

[0009] In another example, a method of rotating microparticles during a chemical reaction can include loading a conductive fluid, a sample, and microparticles that can be surface-activated to react with or bind with a component in the sample into a microfluidic chamber of a microfluidic detection device. The microfluidic detection device can further include a first electrode and a second electrode to generate an electric field along a separation region therebetween through the conductive fluid, and a heating element positioned beneath the separation region to thermally couple with and heat the conductive fluid within the separation region. The method can further include applying a voltage from about 5V to about 40V to the electrodes to generate an electric field across the separation region that can rotate the microparticles and thermally cycling the heating element to heat the conductive fluid in the microfluidic chamber at the separation region and to increase a temperature of the conductive fluid during a chemical reaction that includes the chemical component. In an example, the method can further include optically detecting the luminescence emitted in response to an interaction of a target analyte in the sample with a surface-activation group of the microparticles. In another example, the microparticles can be magnetic and the method can further include holding the microparticles in the conductive fluid at a distance of from about 0.5 pm to about 3 pm away from the heating element.

[0010] When discussing a microfluidic detection device, a microfluidic detection system, and/or a method of rotating microparticles during a chemical reaction herein, such discussions can be considered applicable to one another whether or not they are explicitly discussed in the context of that example. Thus, for example, when discussing a microfluidic chamber of a microfluidic detection device, such disclosure is relevant to and directly supported in the context of the microfluidic detection system, the method of rotating microparticles during a chemical reaction, and vice versa. Terms used herein will have the ordinary meaning in the relevant technical field unless specified otherwise. In some instances, there are terms defined more specifically throughout the specification or included at the end of the present specification, and thus, these terms can have a meaning as described herein.

[0011] Furthermore, the present disclosure includes several figures illustrating specific examples of the technologies described herein. These figures show microfluidic detection devices and microfluidic detection systems that include a variety of components arranged in specific ways depending on the purpose and function of the particular examples depicted. Although the figures illustrate examples that implement the technologies described herein in some detail, these examples also include many features that are optional, which may be changed or removed depending on the particular example. Accordingly, it is understood that the technologies described herein are not limited by the examples shown in the figures. Microfluidic Detection Devices

[0012] In microfluidic detection devices that contain a chamber and utilize particles during detection in general, the particles can become deposited on the floor of the chamber and can clump with one another. Surfaces of the particles that touch the floor of the chamber and are adjacent to one another due to clumping can be blocked. Accordingly, these surfaces cannot be accessible to reactants used in the detection. The microfluidic detection devices herein can rotate particles and can thereby allow for mixing of the reagents and the particles. The rotation can allow for the reactants to be accessible to most or all the surfaces of the particles.

[0013] The present disclosure, as illustrated in FIG. 1, describes microfluidic detection devices 100 that can include a microfluidic chamber 104, a first electrode 110, a second electrode 120, and a heating element 130. When the microfluidic detection device is in use, a conductive fluid can be loaded into the microfluidic chamber and an electrical signal can be sent to the first and second electrode. The electrical signal can cause the electrodes to produce a current and generate an electric field 140, shown by the dashed lines in FIG. 1. The electric field that can be generated can interact with microparticles that can be loaded into the microfluidic chamber and can cause the microparticles to rotate in the conductive fluid at the location of the electric field.

[0014] The microfluidic detection device, in further detail, can be formed in a substrate 102 which can include a microfluidic chamber that can be shaped and/or configured to receive fluid and microparticles. The chamber can be a conical chamber, a cylindrical chamber, a cubed chamber, a polygonal prism chamber, or the like. In one example, the microfluidic chamber can be a U-shape or V-shape cut-out in the substrate. An interior area of the microfluidic chamber is not particularly limited, however, the interior area can hold a volume of fluid and the microparticles. In an example, the interior area of the microfluidic chamber can have a diameter at the widest cross-section that can range from aboutl mm to about 10 mm, from about 1 mm to about 2 mm, from about 3 mm to about 5 mm, from about 5 mm to about 10 mm, from about 2 mm to about 8 mm, or from 1 mm to about 5 mm. A volume of the interior area can range from about 1 pL to about 200 pL, from about 1 pL to about 5 pL, from about 5 pL to about 10 pL, from about 10 pL to about 20 pL, from about 30 pL to about 50 pL, from about 50 pL to about 100 pL, from about 100 pL to about 200 pL, from about 50 pL to about 150 pL, from about 1 pL to about 50 pL, from about 75 pL to about 200 pL, or from about 150 pL to about 200 pL.

[0015] The microfluidic chamber can be formed in a substrate. The material of the substrate can include glass, silicon, polydimethylsiloxane (ROMS), polystyrene, polycarbonate, polymethyl methacrylate, poly-ethylene glycol diacrylate, perflouroaloxy, fluorinated ethylenepropylene, polyfluoropolyether diol methacrylate, polyurethane, cyclic olefin polymer, teflon, copolymers, and combinations thereof. In one example, the substrate can include a hydrogel, ceramic, thermoset polyester, thermoplastic polymer, or a combination thereof. In another example, the substrate can include silicon. In yet another example, the substrate can include a low-temperature co-fired ceramic. A thickness of the substrate that forms walls of the microfluidic chamber can vary and is limited. In one example, the substrate can have a thickness at the smallest diameter ranging from 0.05 mm to 10 mm. In yet other examples, a thickness of the substrate at smallest diameter can vary from 0.5 mm to 2 mm, from 1 mm to 5 mm, from 0.05 mm to 0.8 mm, or from 2 mm to 10 mm.

[0016] In some examples, the substrate can be configured to include an inlet port and an outlet port that can be fluidly connected to the microfluidic chamber. The inlet port and the outlet port can be used to provide fluid to (via the inlet port) and pass fluid from (via the outlet port) the microfluidic chamber. It is noted that the terms “inlet” and “outlet” do not infer that these ports interact with the microfluidic chamber in one direction, though that could be the case. In some instances, there may be occasion for the fluid to flow “backwards” or “bi-directionally,” and thus the terms “inlet port” and “outlet port” can be used because at some point during operation, these two ports act as inflow of fluid and outflow of fluid, respectively, relative to the microfluidic chamber.

[0017] The microfluidic detection device can further include a first electrode and a second electrode. The electrodes can individually be selected from and can include an indium tin oxide transfer electrode, a gold electrode, a platinum electrode, or a combination thereof. In one example the electrodes can be an indium tin oxide transfer electrode. The electrodes, in some examples, can be transparent to luminescence emissions in a detection range. The electrodes may be transparent to fluorescent emissions.

[0018] The first electrode and the second electrode can be operable to generate an electric field in a conductive fluid. The first electrode can provide a first polarity and the second electrode can provide a second polarity that can be opposite the first polarity to create an electric field between the first electrode and the second electrode. The first electrode can provide a positive or a negative charge. A charge from the first electrode can flow through a conductive fluid that can be loaded in the microfluidic chamber. The second electrode can provide a positive or a negative charge that can be opposite a charge provided by the first electrode. A charge of the second electrode can also flow through a conductive fluid that can be loaded in the microfluidic chamber. Accordingly, the opposite charges from the first electrode and the second electrode can create an electric field in the conductive fluid.

[0019] The electric field can span an area between the first electrode and the second electrode. The space between the first electrode and the second electrode can be referred to herein as a “separation region." The separation region can have a distance of from about 10 pm to about 1 cm. In other examples, the separation region can range from about 10 pm to about 1 ,000 pm; from about 100 pm to about 500 pm; from about 10 pm to about 100 pm; from about 10 pm to about 50 pm; from about 20 pm to about 80 pm; from about 50 pm to about 75 pm; from about 250 pm to about 500 pm; from about 500 pm to about 1 ,000 pm; from about 750 pm to about 1 ,000 pm; from about 300 pm to about 600 pm; or from about 400 pm to about 800 pm.

[0020] The first electrode and the second electrode may be located across from one another in the microfluidic chamber. In yet other examples the microfluidic detection device can include additional electrodes. For example the microfluidic detection device can include four electrodes. The additional electrodes can be as described above. The electrodes may be arranged on the same plane. In yet other examples, the electrodes may be arranged in different plans. The electrodes can be arranged as electrode pairs that are across from one another and at ninety degree angles with respect to one another. The electrodes may be equally spaced or substantially equally spaced from one another along the circumferential interior of the microfluidic chamber. In yet other examples, the electrodes can be ring electrodes and can be arranged as concentric circles. An arrangement of the electrodes can be such that the electric field generated can result in an electro-kinetic rotation, Bom-Lertes rotation, or Quincke rotation of microparticles when present in a conductive fluid.

[0021] A heating element may be positioned beneath the separation region between the first electrode and the second electrode. The heating element can be operable to thermally couple with and heat a conductive fluid when the conductive fluid is present in the microfluidic chamber. The heating element may be positioned along a floor of the microfluidic chamber or may be positioned along a ceiling of the microfluidic chamber. In one example, the heating element can be thermally coupled to the microfluidic chamber to heat a conductive fluid in the microfluidic chamber at a rate of about 30 °C/s to about 100 °C/s (e.g., pulses of heat ranging in duration from the order of hundreds of nanoseconds to milliseconds). In another example, the heating element can be positioned to elevate a temperature of a conductive fluid loaded in the microfluidic chamber by aboutlO °C to about 30 °C when pulsed on for 0.1 ps to 1 second. In yet another example, the heating element can be positioned to elevate a temperature of a conductive fluid loaded in the microfluidic chamber by aboutlO °C to about 40 °C when pulsed on for 0.1 ps to 1 second.

[0022] The heating element can be dimensionally as large as or larger in surface area than the separation region. In some examples, the heating element can be dimensionally as large or larger in surface area than one of the surfaces defining the microfluidic chamber, e.g. a floor surface, a side wall surface, a ceiling surface, etc. The types of heating elements that can be used can include a resistive heating element, a field-effect transistor, a p-n junction diode, a thin film heater, a thermal diode, or a combination thereof. In one example, the heating element can include a resistive heating element. In another example, the heating element can include a resistive heating element and a p-n junction diode. In yet another example, the heating element can include a resistive heating element and a thermistor. In some examples, the heating element can include platinum, aluminum, copper, gold, silver, tantalum, titanium, nickel, tin, zinc, chromium, poly-silicon, germanium, oxides, alloys, and combinations thereof. In one example, the heating element can include silver. In another example the heating element can include poly-silicon.

[0023] In some examples the microfluidic detection device can further include a thermal resistive layer 150, as shown in FIG. 2, that can be thermally coupled to the microfluidic chamber to diffuse heat from a conductive fluid in the microfluidic chamber at a rate of 30 °C/s to 100 °C/s. In one example, the thermal resistive layer can define a portion of a boundary of the microfluidic chamber. The thermal resistive layer can include a heat diffusing material and can be located along a side wall of the microfluidic chamber, under the heating element, or a combination thereof. The heat diffusing material of the thermal resistive layer can include silicon dioxide, silicon nitride, non-electrically conductive oxides, nitride, ceramic materials, plastic, diamond, copper, aluminum, silicon, beryllium oxide, barrium nitride, or a combination thereof. The heat diffusing layer can have an average thickness from about 1 pm to about 1 ,000 pm, but more typically from about 1 pm to about 200 pm, from about 5 pm to about 20 pm, from about 10 pm to about 50 pm, or from about 50 pm to about 150 pm.

[0024] In yet other examples the microfluidic detection device can further include a dielectric layer 160, as shown in FIG. 2, can be present to prevent current flow from a conductive fluid to the heating element. The dielectric layer can act as an insulating material. The dielectric layer can include a material selected from kapton, polyimmide, Teflon, silicon oxide, silicon nitride, or a combination thereof. In another example, the dielectric layer can include polyimmide, silicon oxide, silicon nitride of a combination thereof. The dielectric layer can have an average thickness from about 1 pm to about 300 pm, from about 1 pm to about 100 pm, from about 100 pm to about 200, pm, from about 200 pm to about 300 pm, from about 1 pm to about 10 pm, from about 1 pm to about 5 pm, from about 5 to about 25 pm, from about 50 pm to about 75 pm, from about 75 pm to about 100 pm, from about 60 pm to about 80 pm, from about 125 pm to about 175 pm, from about 250 pm to about 300 pm, or from about 175 pm to about 250 pm.

[0025] In some examples, the microfluidic device can include multiple microfluidic chambers, electrodes, and heating elements. The microfluidic device can include an array of microfluidic chambers. The additional microfluidic chambers can be arranged in parallel, in series, or a combination thereof. The microfluidic detection device may be an on-chip, internally controlled, lab-on-a-chip device.

Microfluidic Detection Systems

[0026] The present disclosure also describes microfluidic detection systems. Microfluidic detection systems can include microfluidic detection devices as described above together with additional components. The additional components can include microparticles, conductive fluid, an illumination source, luminescence detection devices, or combinations thereof. In an example, the microfluidic detection system 300 can include a microfluidic detection device 100, as described above, examples of which were illustrated in FIGS. 1 and 2, and microparticles 200 that can include a core 202 and can be surface-activated with an interactive surface group or ligand 204 to react with or bind to a chemical component carried by or to be carried by the conductive fluid when present. See FIG. 3. In yet other examples, the microfluidic detection system can include a microfluidic detection device, microparticles, and a conductive fluid. In a further example the microfluidic detection system can include a microfluidic detection device, microparticles, a conductive fluid, and a luminescence detection device.

[0027] The microparticles, in further detail, can be any particle of a material that may be surface-activated to react or bind with a chemical component and sized to fit within an interior space of the microfluidic chamber. The microparticles can include a core material with a ligand attached to a surface of the core material. Core materials can include melamine resin, polystyrene, polymethacrylate, silica, silicon, SUS, iron, iron oxide, cobalt, cobalt oxide, or a combination thereof. In some examples, the microparticles can include a material that can provide magnetic properties to the microparticles and the microparticles can be magnetic. In other examples, the microparticles can further include a shell between the core and the surface-activation groups and the shell can be selected from polymeethacrylate, silica, or a combination.

[0028] A surface of the microparticles can be surface-activated to react or bind with a chemical component. Surface-activation can include interactive surface groups or ligands on an exterior surface of the core of the microparticles. An exterior of the microparticles can be surface-activated with interactive surface groups that can interact with a chemical component of a sample or may include a covalently attached ligand. In some examples, the ligand can include proteins, antibodies, antigens, nucleic acid primers, nucleic acid probes, amino groups, carboxyl groups, epoxy groups, tosyl groups, sulphydryl groups, or the like. In one example, the ligand can be a nucleic acid probe. The ligand can be selected to correspond with and to bind with the chemical component. The ligand may vary based on the type of chemical component targeted for isolation from the sample. For example, the ligand can include a nucleic acid probe when isolating a biological component that includes a nucleic acid sequence. In another example, the ligand can include an antibody when isolating a biological component that includes antigen. In one example, the microparticles can be surface-activated to bind to RNA. Thus RNA molecules can be bound to the surface of the microparticles. Commercially available examples of microparticles that are surface-activated can include those sold under the trade name DYNABEADS®, available from ThermoFischer Scientific (USA).

[0029] In some examples, the system can include a mixture of microparticles having different surface-activation groups. This can allow for different microparticles to be rotated at different frequencies. For example, microparticles A can have a surface activation group A and the microparticles can be known to rotate at a frequency A generated by an electric field; whereas, microparticles B can have a surface activation group B and the microparticles B can be known to rotate at a frequency B generated by an electric field. Adjusting a frequency range of the electric field can allow for different types of microparticles to be independently manipulated and rotated, while other types of microparticles may settle within the microfluidic chamber.

[0030] The microparticles can have an average core particle size that can range from about 1 pm to about 10 pm. In yet other examples, the microparticles can have an average core particle size that can range from about 1 pm to about 5 pm, from about 2 pm to about 8 pm, from about 5 pm to about 10 pm, or from about 3 pm to about 6 pm. The term “average core particle size" describes a diameter or average diameter of the core of the particles, which may vary, depending upon the morphology of the individual core of the particle. A shape of the core of the microparticles can be spherical, irregular spherical, rounded, semi-rounded, discoidal, angular, sub-angular, cubic, cylindrical, or any combination thereof. In one example, the core of the particles can include spherical particles, irregular spherical particles, or rounded particles. The shape of the core of the microparticles can be spherical and uniform, which can be defined herein as spherical or near-spherical, e.g., having a sphericity of >0.84. Thus, any individual particles having a sphericity of <0.84 are considered non-spherical (irregularly shaped). The particle size of the substantially spherical core microparticle may be provided by its diameter, and the particle size of a non-spherical core microparticle may be provided by its average diameter (e.g., the average of multiple dimensions across the particle) or by an effective diameter, e.g., the diameter of a sphere with the same mass and density as the non-spherical microparticle.

[0031] In some examples, the microparticles can be coordinated in size to a surface of the electrodes of the microfluidic device that may contact a conductive fluid when loaded therein. A ratio of the linear measurements of the areas of the electrodes that may be contacted with a conductive fluid to the exterior surface of the core of the microparticles can range from about 2:1 to about 5:1. In yet other examples, the ratio can range from about 3: 1 to about 4: 1 , from about 2: 1 to about 4: 1 , or from about 3: 1 to about 5:1. In yet other examples, the microparticles can be coordinated in size with a separation distance between the first electrode and the second electrode. For example, the separation distance between the electrodes can range from about three times to about ten times an average core particle size of the microparticles.

[0032] In some examples, the system can further include a conductive fluid. The conductive fluid can be any fluid that includes charges or charged carriers that can be moved with an electric field, such as ions. The conductive fluid can have a conductivity that can range from about 0.3 S/m to about 150 S/m, from about 0.3 S/m to about 1 S/m, from about 3 S/m to about 10 S/m, from about 30 S/m to about 100 S/m,, from about 100 S/m to about 150 S/m, from about 0.3 to about 25 S/m, from about 25 to about 75 S/m, or from about 75 to about 150 S/m. The conductive fluid may be selected from water with a solute therein, saline, phosphate buffer, phosphate-buffered saline, tris buffer, potassium acetate buffer, potassium phosphate buffer, phosphate buffered sucrose, hepes buffered saline, BES-buffered solution, Hanks balanced salt solution, oil with ions present, or a combination thereof. In yet another example, the conductive fluid can include saline, phosphate-buffered saline, oil, or a combination thereof. In some examples, the conductive fluid can be saline or phosphate-buffered saline.

[0033] In further examples, the system can include a luminescence detection device coupled to the microfluidic detection device. The luminescence detection device can be optically associated with the microfluidic chamber and can detect an optical emission therefrom. The luminescence detection device can be selected from a single-color illumination and detection imaging system, a multi-color illumination and detection imaging system, an electrochemical detection system, an optical photodiode, or a combination thereof. In one example, a luminescence detection device can include a pin-photodiode, an avalanche photodiode, a phototransistor, a multi-junction photodiode, a charge coupling device, a complimentary metal-oxide semiconductor, a photo-sensor, a photo-resistor, a pyroelectric detector, a thermopile, or a combination thereof. In one other example, a luminescence detection device can include a pin-photodiode. In another example, a luminescence detection device can include a multi-junction photodiode. In an example, a luminescence detection device can include a fluorimeter, a photoluminescence spectrometer, an excitation light source, an optical filter, or a combination thereof.

[0034] The luminescence detection device can be sized to span the entire area along a surface of the microfluidic chamber. In another example, the luminescence detection device can be sized to span one-quarter to three-quarters of an entire area along a surface of the microfluidic chamber. In a further example, the luminescence detection device can be sized to span half to three-quarters of the area of a surface of the microfluidic chamber.

[0035] In some examples, the system may further include a magnetic field generator that can generate a magnetic field for moving microparticles that are magnetic. In some examples, the magnetic field generator can be a magnet, a ring magnet, or a current carrying wire. Applying the magnetic field, magnetic field motion, and/or differing magnetic field gradients can attract microparticles that are magnetic. The magnetic field may be turned on and off by introducing electric current/voltage to the magnetic field generator. The magnetic field generator can be permanently placed, can be movable along the vessel, or can be movable in position and/or out of position to effect movement of the microparticles.

[0036] The magnetic field generator may create a force capable of pulling the microparticles downward through a conductive fluid toward a floor surface and the heating element of the microfluidic detection device, or create a force capable of holding the microparticles at a location in the conductive fluid, or a combination thereof. When the magnetic field generator is turned off or not in appropriate proximity, the microparticles can reside in conductive fluid until gravity pulls the microparticles downward towards the floor surface. The rate at which gravity pulls the microparticles through the conductive fluid can be based on a mass of the microparticles, a quantity of the microparticles, a size of the microparticles, a density of the conductive fluid, and a viscosity of the conductive fluid.

[0037] In an example, the magnetic field generator may be moveable in position, out of position, or at variable positions to effect downward movement, rate of movement, or to promote little to no movement of the microparticles. In another example, the magnetic field generator can be positioned adjacent to a side of the microfluidic chamber. In yet other examples, a magnetic field generator can be positioned beneath the heating element of the microfluidic chamber. The magnetic field generator may be an integrated component of the microfluidic detection device or can be a completely separate device from the microfluidic detection device.

[0038] The system may further indude a hardware controller operable to generate a command for the system to act in a designated manner. For example, the hardware controller can generate a command to control operation of the first electrode, the second electrode, the heating element, or a combination thereof. In yet other examples, the hardware controller can be used to generate a command to the first electrode, the second electrode, the heating element, the luminescence detection device, or a combination thereof. The hardware controller may be used to send a signal to the first electrode, the second electrode, or a combination thereof to produce an electric field. The hardware controller may be used to signal the heating element to turn on and to heat a conductive fluid in the microfluidic chamber to a specified temperature or to cycle on and off. The hardware controller may be used to send a command to a luminescence detection device to detect an optical emission from the microfluidic chamber.

[0039] A configuration of the hardware controller is not particularly limited and can include circuitry that can be positioned to interact with a component of the system. For example, the circuitry can include resistors, transistors, capacitors, inductors, diodes, light emitting diodes, transistors, converters, conductive wires, conductive tracers, photosensitive components, thermal sensitive components, and the like. The circuitry can be an electrical communication with circuity or components inside of the microfluidic chamber via a wire, a trace, a network of wires, a network of traces, an electrode, a conductive pad, and/or any other electrical communication structure that may or may not be embedded in the microfluidic detection device. In one example, the hardware controller can include signal generators, an amplifier, or a combination thereof. Method of Rotating Microparticles During a Chemical Reaction

[0040] A flow diagram of a method 400 of rotating microparticles during a chemical reaction is shown in FIG. 4. The method can include loading 410 a conductive fluid, a sample, and microparticles that are surface-activated to react with or bind with a chemical component in the sample into a microfluidic chamber of a microfluidic detection device. The microfluidic detection device can further include a first electrode and a second electrode to generate an electric field along a separation region therebetween through a conductive fluid and a heating element positioned beneath the separation region to thermally couple with and heat the conductive fluid within the separation region. The method can also include applying 420 a voltage from about 5V to about 40V to the electrodes to generate an electric field across the separation region which can rotate the microparticles, and thermally cycling 430 the heating element to heat the conductive fluid in the microfluidic chamber at the separation region and to increase a temperature of the conductive fluid during a chemical reaction that includes the chemical component of interest.

[0041] The loading in further detail can include placing the conductive fluid, a sample, and the microparticles into the microfluidic chamber. The loading can include simultaneous loading as the conductive fluid, sample, microparticles, or the combination thereof may be premixed before loading or can include subsequent separate and individual loading of the conductive fluid, sample, and/or microparticles. The loading may include passing the conductive fluid, sample, microparticles, or the combination thereof through a microfluidic inlet and/or microfluidic channels of the microfluidic detection device. In some examples, the microparticles may be preloaded into the microfluidic chamber.

[0042] Applying a voltage to the electrodes to generate an electric field across the separation region can include applying a voltage that can range from about 5 V to about 40 V, from about 10 V to about 30 V, from about 5 V to about 25 V, from about 5 V to about 10 V, or from about 20 V to about 40 V to the electrodes. A frequency of the AC voltage required to cause the microparticles to rotate can range from about 1 kHz to about 10 MHz, from about 1kHz to about 500 kHz, from about 100 kHz to about 300 kHz, from about 50 kHz to about 400 kHz, from about 200 kHz to about 800 kHz, from about 500 kHz to about 1 ,000 kHz, from about 1 ,000 kHz to about 10 MHz, or from about 5 MHz to about 10 MHz. The voltage applied can result in the formation of an electric field in the conductive fluid in a region of the fluid surrounding the particles and between the electrodes. The electric field can interact with a charge of the microparticles and can cause the microparticles to rotate in the conductive fluid. The rotating can expose exterior surfaces of the microparticles that may otherwise be blocked due to clumping or settling of the microparticles. In some examples, when a variety of microparticles are present, applying the voltage can include alternating an amount of the voltage to create different frequencies which can cause some types of microparticles to rotate while allowing other types of microparticles to be unaffected by the electric field. The electrodes can cause the microparticles to be suspended and to rotate at a distance of about 1 pm above the electrode.

[0043] Thermally cycling of the heating element, in further detail, can include alternating heating and cooling of the conductive fluid. The thermal cycling may include turning the heating element on and off. In one example, the thermal cycling involves elevating a temperature of the conductive fluid loaded in the microfluidic chamber by about 10 °C to about 40 °C when pulsed on for 0.1 ps to 10 ps and diffusing heat from the conductive fluid loaded in the microfluidic chamber in between pulses by 10 °C to 40 °C within about 1 ms to about 100 ms. The thermal cycling temperatures and duration may depend on the component of interest. A voltage can be applied to the electrodes during thermal cycling thereby causing the microparticles to rotate during thermal cycling, or a voltage can be applied in between the heating and cooling of the thermal cycling such that the particles are rotated and then heated. Rotating the microparticles during thermal cycling can allow for increased surface exposure of the microparticles while thermal cycling allowing for additional reactions to occur.

[0044] In some examples, the method can further include optically detecting the luminescence emitted in response to an interaction of a target analyte in the fluid with a surface-activation group of the microparticles. The luminescence may be emitted at a surface of the microparticles, or in the fluid within the microfluidic chamber. The luminescence emitted may depend on the chemical reaction.

[0045] In yet other examples, the method can further include holding the microparticles in the conductive fluid at a distance of from about 0.5 pm to about 3 pm away from the heating element. A magnetic field generator in combination with microparticles that are magnetic may be used to hold the microparticles in a desired location/region of the conductive fluid. In yet other examples, the microparticles may be held at a distance of from about 0.5 pm to about 2 pm, from about 0.5 pm to about 1.5 pm, or from 1 pm to about 3 pm away from the heating element.

Definitions

[0046] It is 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.

[0047] The term "about" as used herein, when referring to a numerical value or range, allows for a degree of variability in the value or range, for example, within 10%, or, in one aspect within 5%, of a stated value or of a stated limit of a range. The term “about” when modifying a numerical range is also understood to include as one numerical subrange a range defined by the exact numerical value indicated, e.g., the range of about 1 wt% to about 5 wt% includes 1 wt% to 5 wt% as an explicitly supported sub-range.

[0048] As used herein, a plurality of items, structural elements, compositional elements, and/or materials may be presented in a common list for convenience. However, these lists should be construed as though the individual member of the list is identified as a separate and unique member. Thus, no individual member of such list should be construed as a de facto equivalent of any other member of the same list solely based on presentation in a common group without indications to the contrary.

[0049] Concentrations, amounts, and other numerical data may be expressed or presented herein in a range format. A range format is used merely for convenience and brevity and thus should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range, but also to include individual numerical values or sub-ranges encompassed within that range as if numerical values and sub-ranges are explicitly recited. As an illustration, a numerical range of “1 wt% to 5 wt%” should be interpreted to include not only the explicitly recited values of about 1 wt% to about 5 wt%, but also to include individual values and sub-ranges within the indicated range. Thus, included in this numerical range are individual values such as 2, 3.5, and 4 and sub-ranges such as from 1-3, from 2-4, and from 3-5, etc. This same principle applies to ranges reciting one numerical value. Furthermore, such an interpretation should apply regardless of the breadth of the range or the characteristics being described.

Claims

CLAIMS What is Claimed Is:

1. A microfluidic detection device, comprising: a microfluidic chamber; a first electrode and a second electrode to generate an electric field along a separation region therebetween when a conductive fluid is carried within the microfluidic chamber at a separation region; and a heating element positioned within the separation region to thermally couple with and heat the conductive fluid when the conductive fluid is present in the separation region.

2. The microfluidic detection device of claim 1 , wherein the separation region between the electrodes is partially defined by a distance between the first electrode and the second electrode, wherein the distance is from about 10 pm to about 1 cm

3. The microfluidic detection device of claim 1 , wherein the electrodes are transparent to fluorescent emission.

4. The microfluidic detection device of claim 1 , wherein the electrodes are positioned to act on surface-activated microparticles carried by a conductive fluid and positioned within the separation region to provide electro-kinetic rotation, Bom-Lertes rotation, or Quincke rotation.

5. The microfluidic detection device of claim 1 , wherein the heating element or portion thereof positioned within the separation region is dimensionally as large or larger in surface area as compared to a linear distance between the electrodes.

6. A microfluidic detection system, comprising: a microfluidic detection device including, a microfluidic chamber, a first electrode and a second electrode to generate an electric field along a separation region therebetween when a conductive fluid is carried within the microfluidic chamber at a separation region, and a heating element positioned within the separation region to thermally couple with and heat the conductive fluid when the conductive fluid is present in the separation region; and microparticles that are surface-activated to react with or bind to a chemical component carried by or to be carried by the conductive fluid when present.

7. The system of claim 6, wherein the microparticles have an average core particle size ranging from about 1 pm to about 10 pm.

8. The system of claim 6, wherein the system further includes the conductive fluid and the conductive fluid further operates as a heat sink.

9. The system of claim 6, wherein a ratio of a surface area of the first electrode and the second electrode at surfaces that act upon the conductive fluid to a size of an exterior surface area of a smallest particle of the microparticles ranges from about 2:1 to about 5:1.

10. The system of claim 6, further comprising a luminescence detection device coupled to the microfluidic detection device, wherein the luminescence detection device is selected from a single-color illumination and detection imaging system, a multi-color illumination and detection imaging system, an electrochemical detection system, an optical photodiode, or a combination thereof.

11. The system of claim 6, wherein the microparticles are magnetic and the system further includes a magnetic field generator positioned adjacent to the heating element.

12. The system of claim 6 further comprising a computer for controlling operation of the first electrode, the second electrode, the heating element, or a combination thereof.

13. A method of rotating microparticles during a chemical reaction, comprising: loading a conductive fluid, a sample, and microparticles that are surface-activated to react with or bind with a chemical component in the sample into a microfluidic chamber of a microfluidic detection device, the microfluidic detection device including a first electrode and a second electrode to generate an electric field along a separation region therebetween where the conductive fluid resides and also including a heating element positioned within the separation region to thermally couple with and heat the conductive fluid within the separation region; applying a voltage from about 5V to about 40V to the electrodes to generate the electric field to rotate the microparticles; and thermally cycling the heating element to heat the conductive fluid in the microfluidic chamber at the separation region and to increase a temperature of the conductive fluid during a chemical reaction that includes the chemical component.

14. The method of claim 13, further comprising optically detecting the luminescence emitted in response to an interaction of a target analyte in the sample with a surface-activation group of the microparticles.

15. The method of claim 13, wherein the microparticles are magnetic and the method further includes holding the microparticles in the conductive fluid at a distance of from about 0.5 pm to about 3 pm away from the heating element.