WO2022081132A1 - Heating a solution inside a microreaction chamber with embedded magnetic particles - Google Patents

Heating a solution inside a microreaction chamber with embedded magnetic particles Download PDF

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Publication number
WO2022081132A1
WO2022081132A1 PCT/US2020/055278 US2020055278W WO2022081132A1 WO 2022081132 A1 WO2022081132 A1 WO 2022081132A1 US 2020055278 W US2020055278 W US 2020055278W WO 2022081132 A1 WO2022081132 A1 WO 2022081132A1
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WO
WIPO (PCT)
Prior art keywords
magnetic particles
temperature
microreaction chamber
planar surface
chamber
Prior art date
Application number
PCT/US2020/055278
Other languages
French (fr)
Inventor
Alexander Govyadinov
Viktor Shkolnikov
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Hewlett-Packard Development Company, L.P.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hewlett-Packard Development Company, L.P. filed Critical Hewlett-Packard Development Company, L.P.
Priority to PCT/US2020/055278 priority Critical patent/WO2022081132A1/en
Publication of WO2022081132A1 publication Critical patent/WO2022081132A1/en

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Classifications

    • H—ELECTRICITY
    • H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
    • H05B—ELECTRIC HEATING; ELECTRIC LIGHT SOURCES NOT OTHERWISE PROVIDED FOR; CIRCUIT ARRANGEMENTS FOR ELECTRIC LIGHT SOURCES, IN GENERAL
    • H05B6/00—Heating by electric, magnetic or electromagnetic fields
    • H05B6/02—Induction heating
    • H05B6/10—Induction heating apparatus, other than furnaces, for specific applications
    • H05B6/105—Induction heating apparatus, other than furnaces, for specific applications using a susceptor
    • H05B6/106—Induction heating apparatus, other than furnaces, for specific applications using a susceptor in the form of fillings
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01F—MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
    • H01F1/00—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties
    • H01F1/01—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties of inorganic materials
    • H01F1/03—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties of inorganic materials characterised by their coercivity
    • H01F1/12—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties of inorganic materials characterised by their coercivity of soft-magnetic materials
    • H01F1/34—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties of inorganic materials characterised by their coercivity of soft-magnetic materials non-metallic substances, e.g. ferrites
    • H01F1/36—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties of inorganic materials characterised by their coercivity of soft-magnetic materials non-metallic substances, e.g. ferrites in the form of particles
    • H01F1/37—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties of inorganic materials characterised by their coercivity of soft-magnetic materials non-metallic substances, e.g. ferrites in the form of particles in a bonding agent
    • H—ELECTRICITY
    • H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
    • H05B—ELECTRIC HEATING; ELECTRIC LIGHT SOURCES NOT OTHERWISE PROVIDED FOR; CIRCUIT ARRANGEMENTS FOR ELECTRIC LIGHT SOURCES, IN GENERAL
    • H05B2206/00—Aspects relating to heating by electric, magnetic, or electromagnetic fields covered by group H05B6/00
    • H05B2206/02—Induction heating
    • H05B2206/023—Induction heating using the curie point of the material in which heating current is being generated to control the heating temperature

Definitions

  • FIG. 1 illustrates a method of heating a solution for a temperaturesensitive reaction, in accordance with the present disclosure.
  • FIG. 2 illustrates an example apparatus for heating a solution inside a microreaction chamber, in accordance with the present disclosure.
  • FIG. 3 illustrates an example apparatus including a microreaction chamber having a multi-walled polymeric layer, in accordance with the present disclosure.
  • FIG. 4 illustrates an example apparatus including a microreaction chamber having a polymeric layer on all surfaces inside the microreaction chamber, in accordance with the present disclosure.
  • FIGs. 5A, 5B, and 5C illustrate various example designs of an apparatus including a microreaction chamber having a polymeric layer, in accordance with the present disclosure.
  • FIG. 6 illustrates an example apparatus including a plurality of longitudinal ridges, in accordance with the present disclosure.
  • FIG. 7 illustrates an example apparatus including a plurality of cooling chambers, in accordance with the present disclosure.
  • FIG. 8 illustrates an example apparatus including a plurality of cooling chambers, in accordance with the present disclosure.
  • Applications for heat exchanging chemical reactions may encompass organic, inorganic, biochemical and molecular reactions, among others.
  • chemicals may be heated to achieve the activation energy for the reaction.
  • temperature-sensitive chemical reactions include isothermal nucleic acid amplification, thermal cycling amplification, such as polymerase chain reaction (PGR), ligase chain reaction (LCR), self-sustained sequence replication, enzyme kinetic studies, homogenous ligand binding assays, and more complex biochemical mechanistic studies including complex temperature changes.
  • a variety of designs may be used for heat transfer, such as water baths, air baths, and solid blocks such as aluminum.
  • a block of aluminum having as many as ninety-six conical reaction tubes may be heated and cooled either by a Peltier heating/cooling apparatus, or by a closed-loop liquid heating/cooling system, flowing through channels machined into the aluminum block.
  • heating and cooling rates are generally about 1 ° C./sec resulting in longer processing times.
  • these instruments have large thermal masses in order to achieve temperature uniformity, and take a long time (and or a large heating/cooling power source) to heat and to cool.
  • PCR is a method used in molecular biology to make many copies of a nucleic acid segment. Using PCR, a copy (or more) of a nucleic acid sequence is exponentially amplified to generate thousands to millions or more copies of that particular nucleic acid segment. Many methods of PCR include thermal cycling, which exposes reactants to repeated cycles of heating and cooling to permit different temperature-dependent reactions to occur.
  • thermocycler also referred to as a “thermal cycler”.
  • a thermocycler includes a thermal block with holes where tubes holding the reaction mixtures can be inserted. The cycler then raises and lowers the temperature of the block in discrete, preprogrammed steps.
  • many devices used for temperature cycling, including thermocyclers engage in indirect temperature measurement and do not control the temperature inside the reaction volume. Indirect measurement of the temperature of a reaction volume may be problematic, particularly for multitemperature reactions such as PCR.
  • gradients in temperature across a reaction volume may result in a reaction proceeding in a non-uniform manner, which reduces the accuracy of the assay (e.g., chemical reaction) being performed.
  • the assay e.g., chemical reaction
  • each cycle doubles the amount of a target nucleic acid. After n cycles, 2 n copies of the target nucleic acid may be obtained. Under conditions of non-uniform temperature, after n cycles, /(" copies of the target may be achieved, where k ⁇ 2 is an unknown, and may be unstable. Thus the quantitative power of the assay decreases.
  • heating a solution inside a microreaction chamber with embedded magnetic particles allows for precise temperature control of a solution inside a microfluidic chamber with minimal temperature gradients, without temperature sensing devices and feedback control, and therefore in a low cost manner.
  • a method for heating a solution inside a microreaction chamber with embedded magnetic particles includes placing a microreaction chamber into an oscillating magnetic field, wherein a plurality of magnetic particles are embedded on a surface of the microreaction chamber.
  • the plurality of magnetic particles include a plurality of magnetic particles of a first type, wherein the first type of magnetic particles have a first Curie temperature corresponding with a temperature of a temperature-sensitive reaction, and a first resonance frequency at which the magnetic particles respond to an oscillating magnetic field.
  • the plurality of magnetic particles further include a plurality of magnetic particles of a second type, wherein the second type of magnetic particles have a second Curie temperature corresponding with a temperature of the temperature-sensitive reaction, and a second resonance frequency at which the magnetic particles respond to the oscillating magnetic field.
  • the method further includes heating a solution inside the microreaction chamber to a particular temperature associated with the plurality of magnetic particles by maintaining the oscillating magnetic field at a resonance frequency selected from the first resonance frequency and the second resonance frequency.
  • an apparatus for heating a solution inside a microreaction chamber with embedded magnetic particles includes a base substrate extending along a first planar surface, and a top wall extending along a second planar surface generally parallel to the first planar surface.
  • the apparatus further includes a first side wall extending along a third planar surface generally perpendicular to the first planar surface and second planar surface, and a second side wall extending along a fourth planar surface generally parallel to the third planar surface, wherein the base substrate, the top wall, the first side wall, and the second side wall form a microreaction chamber.
  • the apparatus further includes a polymeric layer disposed on the first planar surface, the second planar surface, the third planar surface, or the fourth planar surface, wherein the polymeric layer includes a plurality of magnetic particles having a Curie temperature at a target temperature for the microreaction chamber.
  • an apparatus for heating a solution inside a microreaction chamber with embedded magnetic particles includes a microreaction chamber extending a length of the apparatus.
  • the microreaction chamber includes a base substrate, a top wall extending generally parallel to the base substrate, a first side wall extending generally perpendicular to the base substrate and the top wall, and a second side wall extending generally parallel to the first side wall.
  • the apparatus further includes a polymeric layer disposed on a surface of the microreaction chamber, wherein the polymeric layer includes a plurality of magnetic particles having a Curie temperature at a target temperature for the microreaction chamber.
  • the apparatus includes a cooling chamber extending the length of the apparatus and generally parallel to the microreaction chamber.
  • FIG. 1 illustrates a method 100 of heating a solution for a temperature-sensitive reaction, in accordance with the present disclosure.
  • a solution included in a microreaction chamber refers to or includes any combination of reagents, buffers, solvents, sample, and other liquid or solid components that may be involved in a temperature-sensitive reaction.
  • reagents buffers, solvents, sample, and other liquid or solid components that may be involved in a temperature-sensitive reaction.
  • buffers buffers
  • solvents sample
  • sample sample
  • other liquid or solid components that may be involved in a temperature-sensitive reaction.
  • several components and reagents may be included in the solution.
  • a nucleic acid template such as a DNA template (e.g., double-stranded DNA) that contains the target sequence to be amplified, an enzyme that polymerizes new nucleic acid strands (e.g., a polymerase enzyme such as DNA polymerase, e.g., Taq DNA polymerase), two nucleic acid primers (oligonucleotides, e.g., single-stranded) that are complementary to the 3' (three prime) ends of each of the sense and antisense strands of the nucleic acid target, nucleoside triphosphates (NTPs) such as deoxyribonucleotide triphosphates (dNTPs) and ribonucleoside triphosphates (rNTPs), and a buffer solution providing a chemical environment for amplification and stability of the polymerase.
  • Specific buffer solutions may include bivalent cations, such as magnesium (Mg) or manganese (Mn) ions, and
  • a microreaction chamber refers to or includes an enclosed structure for performing a chemical reaction.
  • the microreaction chamber may have dimensions ranging from approximately 5 pm width x 5 pm length x 5 pm depth to about 1 millimeter (mm) width x 1 mm length x 1 mm depth. Examples are not limited to microreaction chambers having a same width, length, and depth, and each of the measurements may be different.
  • the microreaction chamber has dimensions of approximately 20 urn x 20 urn x 20 urn.
  • the microreaction chamber is illustrated herein as generally straight, examples are not so limited and the microreaction chamber may have a serpentine shape, a chevron shape, among other formations.
  • the method 100 includes placing a microreaction chamber 101 into an oscillating magnetic field.
  • a plurality of magnetic particles may be embedded in a layer 105 on the surface of the microreaction chamber101 .
  • the plurality of magnetic particles embedded in the microreaction chamber 101 include a plurality of magnetic particles of a first type, and a plurality of magnetic particles of a second type.
  • the first type of magnetic particles may have a first Curie temperature corresponding with a temperature of a temperature-sensitive reaction, and a first resonance frequency at which the magnetic particles respond to the oscillating magnetic field 103.
  • the plurality of magnetic particles further include a plurality of magnetic particles of a second type, wherein the second type of magnetic particles have a second Curie temperature corresponding with a temperature of the temperature-sensitive reaction, and a second resonance frequency at which the magnetic particles respond to the oscillating magnetic field 103.
  • a Curie temperature refers to or includes a temperature above which certain materials lose their permanent magnetic properties, which can be replaced by induced magnetism. When exposed to an oscillating magnetic field, the plurality of magnetic particles heat up, through hysteresis losses, until they reach their Curie temperature.
  • the Curie temperature is a property of the material comprising the magnetic particles, and relative proportions of materials (as appropriate).
  • the plurality of magnetic particles consist essentially of iron oxide, a soft ferrite, a ferromagnetic material, a ferrimagnetic material, or combinations thereof.
  • Non-limiting example compositions of magnetic particles include iron oxide (Fe2Os), soft ferrites ranging from spinel-type ferrites (MeFe2C>4) to manganese-zinc ferrite (Mn a Zn(i-a)Fe2O4), nickel-zinc ferrite (Ni a Zn(i- a )Fe2O4), and a nickel-iron alloy (Ni-Fe (80:20)), among others.
  • the value of ‘a’ may be selected to change the particular alloy to have a particular Curie temperature.
  • the hysteresis losses in the magnetic particles cause the temperature of the magnetic particles to rise, eventually reaching the Curie temperature for the magnetic particle.
  • each of the magnetic particles have a range of resonance frequencies at which the magnetic particles lose heat by hysteresis.
  • magnetic particles with a different material composition and different Curie temperature may heat the solution within the microreaction chamber 101 to different respective temperatures.
  • the oscillating magnetic field is illustrated in FIG. 1 by 103-a and 103-b. Particularly, 103-a illustrates magnetic field lines going into the page, whereas 103-b illustrates magnetic field lines coming out of the page.
  • the oscillating magnetic field may be formed using an electromagnetic field (EMF) generator.
  • EMF electromagnetic field
  • FIG. 1 illustrates the oscillating magnetic field extending perpendicular to the microreaction chamber 101 , examples are not so limited.
  • the oscillating magnetic field may also be referred to as oscillating magnetic field 103.
  • the method 100 includes heating a solution 107 inside the microreaction chamber to a particular temperature associated with the plurality of magnetic particles by maintaining the oscillating magnetic field at a resonance frequency selected from the first resonance frequency and the second resonance frequency.
  • the solution 107 may be heated to a particular temperature by maintaining the oscillating magnetic field 103 at a resonance frequency corresponding with the first magnetic particles and/or the second magnetic particles.
  • heating the solution to the first Curie temperature includes heating the first type of magnetic particles to the first Curie temperature
  • heating the solution to the second Curie temperature includes heating the second type of magnetic particles to the second Curie temperature.
  • the type of magnetic particles may be selected for their specific Curie temperatures, such that the Curie temperatures align with a particular target temperature of a temperature-sensitive reaction.
  • the plurality of magnetic particles include a first type of magnetic particles having a first Curie temperature at a first target temperature for the microreaction chamber and a second type of magnetic particles having a second Curie temperature at a second target temperature for the microreaction chamber.
  • method 100 may be used to carry out PCR, among other temperature-sensitive reactions.
  • PCR short sense and antisense oligonucleotides, which delimit the region to be amplified, are added to the solution 107 with the template in a low concentration, a thermostable polymerase and individual nucleotides.
  • the solution may be heated to approximately 95-100° C by exposing the microreaction chamber to an oscillating magnetic field 103 with a first frequency, thereby heating a first type of magnetic particles in the layer 105 to a first Curie temperature.
  • the solution may further by heated to approximately 40-65° C by exposing the microreaction chamber to an oscillating magnetic field 103 with a second frequency, thereby heating a second type of magnetic particles in the layer 105 to a second Curie temperature.
  • the solution may be heated to approximately 70-80° C by exposing the microreaction chamber to an oscillating magnetic field 103 with a third frequency, thereby heating a third type of magnetic particles in the layer 105 to a third Curie temperature.
  • the solution 107 inside the microreaction chamber 101 may be heated to a plurality of different temperatures by altering the resonance frequency of the oscillating magnetic field 103.
  • heating the solution inside the microreaction chamber includes heating the solution to a first temperature associated with the first type of magnetic particles by applying a first resonance frequency to the oscillating magnetic field, and heating the solution to a second temperature associated with the second type of magnetic particles by applying a second resonance frequency to the oscillating magnetic field.
  • heating the solution to the first temperature includes heating the first type of magnetic particles to a Curie temperature of the first type of magnetic particles
  • heating the solution to the second temperature includes heating the second type of magnetic particles to a Curie temperature of the second type of magnetic particles.
  • the method 100 includes selectively activating the first type of magnetic particles or the second type of magnetic particles by changing the resonance frequency of the oscillating magnetic field. For instance, by changing a frequency of the oscillating magnetic field 103, a different respective magnetic particle type may be activated, and a different respective Curie temperature may be achieved.
  • the first Curie temperature and the second Curie temperature are below a melting point of the surface of the microreaction chamber.
  • the magnetic particles heat the solution 107 by induction without melting the walls of the microreaction chamber 101.
  • heating the solution inside the microreaction chamber includes heating the solution to the first temperature associated with the first type of magnetic particles by applying the first resonance frequency to the oscillating magnetic field 103, and heating the solution 107 to the second temperature associated with the second type of magnetic particles by applying the second resonance frequency to the oscillating magnetic field 103.
  • the magnetic particles may be embedded in various surfaces of the microreaction chamber, and may also be embedded into structural elements of the microreaction chamber to locally control temperature.
  • heating pillars may be used to elute nucleic acid material bound to them, to denature bound proteins, lyse cells, and/or to deactivate a bound virus.
  • FIG. 2 illustrates an example apparatus for heating a solution inside a microreaction chamber, in accordance with the present disclosure.
  • apparatus 209 includes a base substrate 211 extending along a first planar surface (e.g., extending along the x-plane), and a top wall 217 extending along a second planar surface generally parallel to the first planar surface.
  • the apparatus 209 further includes a first side wall 215 extending along a third planar surface (e.g., extending along the y-plane) generally perpendicular to the first planar surface and second planar surface, and a second side wall 213 extending generally parallel to the third planar surface.
  • the base substrate 211 , the top wall 217, the first side wall 215, and the second side wall 213 form a microreaction chamber 201 .
  • a polymeric layer 205 may be disposed on the first planar surface, the second planar surface, the third planar surface, or the fourth planar surface, wherein the polymeric layer 205 includes a plurality of magnetic particles 219 having a Curie temperature at a target temperature for the microreaction chamber.
  • FIG. 2 illustrates the polymeric layer 205 being disposed along the first side wall 215, examples are not so limited.
  • the polymeric layer 205 may be disposed on side wall 215, side wall 213, base substrate 211 , top wall 217, or various combinations thereof.
  • Exploded view 212 illustrates the polymeric layer 205 disposed on side wall 215, and exposed to the solution 207 inside microreaction chamber 201 .
  • a polymeric layer refers to or includes a polymeric matrix that contains a plurality of magnetic particles.
  • the polymeric matrix may comprise natural or synthetic polymer matrices.
  • natural polymers include polysaccharides such as dextran, sepharose, polypeptides such as poly-L-aspartate, poly-L-glutamate, polylactides such as poly-P, L- lactide.
  • synthetic polymer matrices include polyvinyl alcohol, polystyrene (derivatives), poly(meth)acrylates and -acrylamides, polypyrroles, polyesters, poly-s-caprolactam, etc. and copolymers also with natural polymers.
  • the magnetic particles are of a size and concentration to keep the polymeric layer 205 transparent for photolithography.
  • the magnetic particles have a diameter of between approximately 50 pm to approximately 5 nanometers (nm).
  • a concentration of magnetic particles in the polymeric layer ranges from approximately 1% by weight to approximately 10% per weight.
  • the polymeric layer 205 may include a plurality of embedded magnetic particles.
  • the polymeric layer 205 may include a first type 219-1 of magnetic particles having a first Curie temperature at a first target temperature for the microreaction chamber and a second type 219-2 of magnetic particles having a second Curie temperature at a second target temperature for the microreaction chamber.
  • the first type 219-1 of magnetic particles may have a Curie temperature for a first temperature of a temperature-sensitive reaction
  • the second type 219- 2 of magnetic particles may have a Curie temperature for a second temperature of the temperature-sensitive reaction.
  • the polymeric layer 205 is semitransparent, enabling optical interrogation of the solution 207 inside the microreaction chamber.
  • FIG. 3 Illustrates an example apparatus including a microreaction chamber having a multi-walled polymeric layer, in accordance with the present disclosure. More particularly, FIG. 3 illustrates an example microreaction chamber wherein the polymeric layer is disposed on the first planar surface, the second planar surface, and the third planar surface.
  • the apparatus 309 illustrated in FIG. 3 includes similar components as apparatus 209 illustrated in FIG. 2. For instance, apparatus 309 includes a base substrate 311 similar to base substrate 21 1 illustrated in FIG. 2, a first side wall 315 similar to side wall 215 illustrated in FIG. 2, a second side wall 313 similar to side wall 213 illustrated in FIG. 2, and a top wall 317 similar to top wall 217 illustrated in FIG.
  • the microreaction chamber 301 may store the solution for the temperature-sensitive reaction.
  • the polymeric layer 305 may be deposited on a plurality of walls lining the microreaction chamber 301 .
  • the polymeric layer 305 may be disposed on the first planar surface, the second planar surface, and the third planar surface.
  • optical performance may be improved by having one wall (e.g., top wall 317) not have a semitransparent polymeric layer. Examples are not limited to the particular arrangement illustrated in FIG. 3, and in some examples the polymeric layer 305 is disposed on the base substrate 311 , the top wall 317, the first side wall 315, and the second side wall 313 of the microreaction chamber.
  • FIG. 4 illustrates an example apparatus including a microreaction chamber having a polymeric layer on all surfaces inside the microreaction chamber, in accordance with the present disclosure.
  • the apparatus 409 illustrated in FIG. 4 includes similar components as apparatus 309 illustrated in FIG. 3.
  • apparatus 409 includes a base substrate 411 similar to base substrate 31 1 illustrated in FIG. 3, a first side wall 415 similar to side wall 315 illustrated in FIG. 3, a second side wall 413 similar to side wall 313 illustrated in FIG. 3, and a top wall 417 similar to top wall 317 illustrated in FIG.
  • the microreaction chamber 401 may store the solution for the temperature-sensitive reaction.
  • the polymeric layer 405 may be deposited on all four walls lining the microreaction chamber 301 .
  • the polymeric layer 305 may be disposed on the first planar surface, the second planar surface, the third planar surface, and the fourth planar surface.
  • FIGs. 5A, 5B, and 50 illustrate various example designs of an apparatus including a microreaction chamber having a polymeric layer, in accordance with the present disclosure.
  • FIG. 5A illustrates apparatus 506,
  • FIG. 5B illustrates apparatus 508, and
  • FIG. 50 illustrates apparatus 510.
  • Each of the apparatuses may be formed by the following process.
  • Magnetic particles may be mixed with a polymer resist to disperse the particles into the polymer resist, and the magnetic polymer resist may be spin coated onto substrate to form the polymeric layer described herein.
  • the resultant layers include the base substrate 511 and polymeric layer 505-a.
  • the resultant material is baked.
  • an etch stop layer may be deposited onto the base substrate 511.
  • the etch stop layer may be an evaporated or sputtered thin metal layer.
  • Another layer of magnetic polymer resist may be spin coat to form polymeric layer 505-b. Apparatus 508 and apparatus 510 may be exposed to lithographically to define the edges of polymeric layers 505-a and 505-b.
  • apparatus 506, apparatus 508, and apparatus 510 may be formed by depositing polymeric layer 505-a by spin-coating or thin film deposition onto base substrate 511.
  • magnetic material is patterned onto layer 505-a by photolithography or an etch process.
  • the microfluidic chamber layer may be deposited on the polymeric layer 505-a by spin coating or thin film deposition of side wall 515 and side wall 513.
  • a second polymeric layer 505-b may be deposited by spin-coating, thin film deposition or hot air lamination method.
  • the second magnetic material may be patterned using a photolithography or etch process.
  • an additional top hat layer 517 may be laminated to increase structural strength of the top hat.
  • the apparatus 506 includes two continuous polymeric layers 505-a and 505-b extending a width of the apparatus 506.
  • the apparatus 508 includes one of the polymeric layers patterned, while the other of the two polymeric layers extends the width of the apparatus.
  • FIG. 5B illustrates polymeric layer 505-a patterned and polymeric layer 505-b extending a width of the apparatus, examples are not so limited, and polymeric layer 505-b may extend a length of the apparatus while polymeric layer 505-a is patterned.
  • both polymeric layer 505-a and polymeric layer 505-b are patterned.
  • FIG. 6 illustrates an example apparatus 609 including a plurality of longitudinal ridges, in accordance with the present disclosure.
  • the apparatus 609 illustrated in FIG. 6 includes similar components as apparatus 209 illustrated in FIG. 2.
  • apparatus 609 includes a base substrate 61 1 similar to base substrate 21 1 illustrated in FIG. 2, a first side wall 615 similar to side wall 215 illustrated in FIG. 2, a second side wall 613 similar to side wall 213 illustrated in FIG. 2, and a top wall 617 similar to top wall 217 illustrated in FIG.
  • walls 615, 617, 611 , and 613 define a microreaction chamber 601.
  • the polymeric layer may be deposited on a plurality of longitudinal ridges 621 -1 , 621 -2, 621 -3, and 621 -4 (collectively referred to herein as longitudinal ridges 621 ).
  • the longitudinal ridges 621 may extend from the base substrate 61 1 toward the top wall 617, and may comprise the polymeric layer described herein.
  • the longitudinal ridges 621 may comprise ridges coated in the polymeric layer.
  • the longitudinal ridges 621 may comprise essentially of the polymeric layer.
  • FIG. 6 illustrates the longitudinal ridges 621 extending from the base substrate 611 to the top wall 617
  • the longitudinal ridges 621 may comprise ribbons of the polymeric layer that are deposited along the base substrate 611 in strips.
  • various apparatuses described herein may include a plurality of longitudinal ridges extending a length of the apparatus along a plane generally parallel to the microreaction chamber, wherein the polymeric layer is embedded in a surface of the plurality of longitudinal ridges.
  • FIG. 7 illustrates an example apparatus including a plurality of cooling chambers, in accordance with the present disclosure.
  • the apparatus 709 may include a microreaction chamber 701 extending a length of the apparatus.
  • the microreaction chamber 701 includes a base substrate 71 1 , a top wall 717 extending generally parallel to the base substrate 711 , and first side wall 723 extending generally perpendicular to the base substrate 71 1 and the top wall 717.
  • the microreaction chamber 701 further includes a second side wall 721 extending generally parallel to the first side wall 723. As illustrated, side wall 713 may extend generally parallel to side wall 721 , and side wall 715 may extend generally parallel to side wall 723.
  • the apparatus 709 may include a polymeric layer 705 disposed on a surface of the microreaction chamber 701 , wherein the polymeric layer includes a plurality of magnetic particles having a Curie temperature at a target temperature for the microreaction chamber. Additionally, the apparatus 709 may include a cooling chamber extending the length of the apparatus and generally parallel to the microreaction chamber 701 . The example in FIG. 7 illustrates two cooling chambers 719 and 720 that extend the length of the apparatus and are generally parallel to the microreaction chamber 701 . As discussed herein, the microreaction chamber 701 may contain a solution 707 for a temperature-sensitive reaction.
  • Cooling chambers 719 and 720 may include a sink that is capable of absorbing heat from the microreaction chamber 701 .
  • a non-limiting example of a sink that may be included in the cooling chambers 719 and 720 is water.
  • the cooling chamber may also include added materials that help identify a relative temperature of the cooling chamber.
  • the cooling chamber includes a volume of a liquid including a temperature sensitive dye. The temperature sensitive dye may change colors when the temperature of the solution in the cooling chamber reaches a threshold temperature.
  • the base substrate, the top wall, the first side wall, or the second side wall include a region of semi-transparent material for optical interrogation of the microreaction chamber.
  • FIG. 7 illustrates the polymeric layer 705 disposed on the inner surface of the microreaction chamber 701
  • the polymeric layer 705 may be arranged in various manners as discussed and illustrated in the foregoing examples.
  • the apparatus 709 includes a plurality of longitudinal ridges extending a length of the apparatus along a plane generally parallel to the microreaction chamber, wherein the polymeric layer is embedded in a surface of the plurality of longitudinal ridges.
  • the polymeric layer 705 may be disposed on the base substrate, the top wall, the first side wall, and the second side wall of the microreaction chamber. However, examples are not so limited. In some examples, the polymeric layer 705 may be disposed on side walls 723 and 721 , as well as base substrate 71 1 , among other non-limiting examples.
  • FIG. 8 illustrates an example apparatus including a plurality of cooling chambers, in accordance with the present disclosure.
  • the apparatus 809 may include additional cooling chambers, as compared to the example illustrated in FIG. 7.
  • the apparatus 809 may include a microreaction chamber 801 extending a length of the apparatus.
  • the microreaction chamber 801 includes a base substrate 811 , a top wall 817 extending generally parallel to the base substrate 811 , and first side wall 823 extending generally perpendicular to the base substrate 811 and the top wall 817.
  • the microreaction chamber 801 further includes a second side wall 821 extending generally parallel to the first side wall 823.
  • side wall 813 may extend generally parallel to side wall 821
  • side wall 815 may extend generally parallel to side wall 823.
  • the apparatus 809 may include a polymeric layer 805 disposed on a surface of the microreaction chamber 801 , wherein the polymeric layer includes a plurality of magnetic particles having a Curie temperature at a target temperature for the microreaction chamber. Additionally, the apparatus 809 may include a cooling chamber extending the length of the apparatus and generally parallel to the microreaction chamber 801 .
  • FIG. 8 illustrates cooling chambers 819, 820, 825 and 827 that extend the length of the apparatus and are generally parallel to the microreaction chamber 801 .
  • a top wall 829 may separate the cooling chamber 827 from the microreaction chamber 801 and the cooling chambers 819 and 820.
  • a base substrate 831 may separate the cooling chamber 825 from the microreaction chamber 801 and the cooling chambers 819 and 820.
  • the microreaction chamber 801 may contain a solution 807 for a temperature-sensitive reaction.
  • Cooling chambers 819, 820, 825, and/or 827 may include a sink that is capable of absorbing heat from the microreaction chamber 801 .
  • a non-limiting example of a sink that may be included in the cooling chambers is water.
  • the cooling chamber may also include added materials that help identify a relative temperature of the cooling chamber.
  • the cooling chamber includes a volume of a liquid including a temperature sensitive dye. The temperature sensitive dye may change colors when the temperature of the solution in the cooling chamber reaches a threshold temperature.
  • the base substrate, the top wall, the first side wall, or the second side wall include a region of semi-transparent material for optical interrogation of the microreaction chamber.

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  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

A method for heating a solution inside a microreaction chamber with embedded magnetic particles includes placing a microreaction chamber into an oscillating magnetic field, wherein a plurality of magnetic particles are embedded on a surface of the microreaction chamber. The plurality of magnetic particles include magnetic particles of a first type and having a first Curie temperature, and a first resonance frequency at which the magnetic particles respond to an oscillating magnetic field. The plurality of magnetic particles further include magnetic particles of a second type with a second Curie temperature, and a second resonance frequency at which the magnetic particles respond to the oscillating magnetic field. The method further includes heating a solution inside the microreaction chamber to a particular temperature associated with the plurality of magnetic particles by maintaining the oscillating magnetic field at a resonance frequency selected from the first resonance frequency and the second resonance frequency.

Description

HEATING A SOLUTION INSIDE A MICROREACTION CHAMBER WITH EMBEDDED MAGNETIC PARTICLES
Background
[0001] There are many applications in the field of chemical processing involving precise control of the temperature of chemicals, as well as the induction of rapid temperature transitions. In these reactions, heat is exchanged between chemicals and their environment to increase or decrease the temperature of the reacting chemicals. In such temperature-sensitive reactions, the temperature change may be controlled in a manner that attains the target temperature, avoids undershooting or overshooting of the temperature, and quickly reaches the target temperature. Such control of temperature may inhibit side reactions, the formation of unwanted bubbles, the degradation of components at certain temperatures, etc., which may occur at temperatures other than the target temperature.
Brief Description of the Drawings
[0002] FIG. 1 illustrates a method of heating a solution for a temperaturesensitive reaction, in accordance with the present disclosure.
[0003] FIG. 2 illustrates an example apparatus for heating a solution inside a microreaction chamber, in accordance with the present disclosure.
[0004] FIG. 3 illustrates an example apparatus including a microreaction chamber having a multi-walled polymeric layer, in accordance with the present disclosure. [0005] FIG. 4 illustrates an example apparatus including a microreaction chamber having a polymeric layer on all surfaces inside the microreaction chamber, in accordance with the present disclosure.
[0006] FIGs. 5A, 5B, and 5C illustrate various example designs of an apparatus including a microreaction chamber having a polymeric layer, in accordance with the present disclosure.
[0007] FIG. 6 illustrates an example apparatus including a plurality of longitudinal ridges, in accordance with the present disclosure.
[0008] FIG. 7 illustrates an example apparatus including a plurality of cooling chambers, in accordance with the present disclosure.
[0009] FIG. 8 illustrates an example apparatus including a plurality of cooling chambers, in accordance with the present disclosure.
Detailed Description
[0010] In the following detailed description, reference is made to the accompanying drawings which form a part hereof, and in which is shown by way of illustration specific examples in which the disclosure may be practiced. It is to be understood that other examples may be utilized and structural or logical changes may be made without departing from the scope of the present disclosure. The following detailed description, therefore, is not to be taken in a limiting sense, and the scope of the present disclosure is defined by the appended claims. It is to be understood that features of the various examples described herein may be combined, in part or whole, with each other, unless specifically noted otherwise.
[0011] Applications for heat exchanging chemical reactions may encompass organic, inorganic, biochemical and molecular reactions, among others. In organic and inorganic reactions, chemicals may be heated to achieve the activation energy for the reaction. Examples of temperature-sensitive chemical reactions include isothermal nucleic acid amplification, thermal cycling amplification, such as polymerase chain reaction (PGR), ligase chain reaction (LCR), self-sustained sequence replication, enzyme kinetic studies, homogenous ligand binding assays, and more complex biochemical mechanistic studies including complex temperature changes.
[0012] A variety of designs may be used for heat transfer, such as water baths, air baths, and solid blocks such as aluminum. For instance, a block of aluminum having as many as ninety-six conical reaction tubes may be heated and cooled either by a Peltier heating/cooling apparatus, or by a closed-loop liquid heating/cooling system, flowing through channels machined into the aluminum block. Because of the large thermal mass of the aluminum block, heating and cooling rates are generally about 1 ° C./sec resulting in longer processing times. Moreover, these instruments have large thermal masses in order to achieve temperature uniformity, and take a long time (and or a large heating/cooling power source) to heat and to cool.
[0013] A particular example of a temperature-sensitive reaction is PCR. PCR is a method used in molecular biology to make many copies of a nucleic acid segment. Using PCR, a copy (or more) of a nucleic acid sequence is exponentially amplified to generate thousands to millions or more copies of that particular nucleic acid segment. Many methods of PCR include thermal cycling, which exposes reactants to repeated cycles of heating and cooling to permit different temperature-dependent reactions to occur.
[0014] In various temperature-sensitive reactions, including PCR, creating repeated cycles of heating and cooling involve the use of a thermocycler (also referred to as a “thermal cycler”). A thermocycler includes a thermal block with holes where tubes holding the reaction mixtures can be inserted. The cycler then raises and lowers the temperature of the block in discrete, preprogrammed steps. However, many devices used for temperature cycling, including thermocyclers, engage in indirect temperature measurement and do not control the temperature inside the reaction volume. Indirect measurement of the temperature of a reaction volume may be problematic, particularly for multitemperature reactions such as PCR. For instance, gradients in temperature across a reaction volume may result in a reaction proceeding in a non-uniform manner, which reduces the accuracy of the assay (e.g., chemical reaction) being performed. For example, for PCR, each cycle doubles the amount of a target nucleic acid. After n cycles, 2n copies of the target nucleic acid may be obtained. Under conditions of non-uniform temperature, after n cycles, /(" copies of the target may be achieved, where k <2 is an unknown, and may be unstable. Thus the quantitative power of the assay decreases.
[0015] In accordance with the present disclosure, heating a solution inside a microreaction chamber with embedded magnetic particles, allows for precise temperature control of a solution inside a microfluidic chamber with minimal temperature gradients, without temperature sensing devices and feedback control, and therefore in a low cost manner.
[0016] In a particular example, a method for heating a solution inside a microreaction chamber with embedded magnetic particles includes placing a microreaction chamber into an oscillating magnetic field, wherein a plurality of magnetic particles are embedded on a surface of the microreaction chamber. In such examples, the plurality of magnetic particles include a plurality of magnetic particles of a first type, wherein the first type of magnetic particles have a first Curie temperature corresponding with a temperature of a temperature-sensitive reaction, and a first resonance frequency at which the magnetic particles respond to an oscillating magnetic field. The plurality of magnetic particles further include a plurality of magnetic particles of a second type, wherein the second type of magnetic particles have a second Curie temperature corresponding with a temperature of the temperature-sensitive reaction, and a second resonance frequency at which the magnetic particles respond to the oscillating magnetic field. The method further includes heating a solution inside the microreaction chamber to a particular temperature associated with the plurality of magnetic particles by maintaining the oscillating magnetic field at a resonance frequency selected from the first resonance frequency and the second resonance frequency.
[0017] As another particular example, an apparatus for heating a solution inside a microreaction chamber with embedded magnetic particles includes a base substrate extending along a first planar surface, and a top wall extending along a second planar surface generally parallel to the first planar surface. The apparatus further includes a first side wall extending along a third planar surface generally perpendicular to the first planar surface and second planar surface, and a second side wall extending along a fourth planar surface generally parallel to the third planar surface, wherein the base substrate, the top wall, the first side wall, and the second side wall form a microreaction chamber. The apparatus further includes a polymeric layer disposed on the first planar surface, the second planar surface, the third planar surface, or the fourth planar surface, wherein the polymeric layer includes a plurality of magnetic particles having a Curie temperature at a target temperature for the microreaction chamber. [0018] As a further example, an apparatus for heating a solution inside a microreaction chamber with embedded magnetic particles includes a microreaction chamber extending a length of the apparatus. The microreaction chamber includes a base substrate, a top wall extending generally parallel to the base substrate, a first side wall extending generally perpendicular to the base substrate and the top wall, and a second side wall extending generally parallel to the first side wall. The apparatus further includes a polymeric layer disposed on a surface of the microreaction chamber, wherein the polymeric layer includes a plurality of magnetic particles having a Curie temperature at a target temperature for the microreaction chamber. Moreover, the apparatus includes a cooling chamber extending the length of the apparatus and generally parallel to the microreaction chamber.
[0019] Turning now to the figures, FIG. 1 illustrates a method 100 of heating a solution for a temperature-sensitive reaction, in accordance with the present disclosure. As used herein, a solution included in a microreaction chamber refers to or includes any combination of reagents, buffers, solvents, sample, and other liquid or solid components that may be involved in a temperature-sensitive reaction. In the example of PCR, several components and reagents may be included in the solution. Among these components are, a nucleic acid template, such as a DNA template (e.g., double-stranded DNA) that contains the target sequence to be amplified, an enzyme that polymerizes new nucleic acid strands (e.g., a polymerase enzyme such as DNA polymerase, e.g., Taq DNA polymerase), two nucleic acid primers (oligonucleotides, e.g., single-stranded) that are complementary to the 3' (three prime) ends of each of the sense and antisense strands of the nucleic acid target, nucleoside triphosphates (NTPs) such as deoxyribonucleotide triphosphates (dNTPs) and ribonucleoside triphosphates (rNTPs), and a buffer solution providing a chemical environment for amplification and stability of the polymerase. Specific buffer solutions may include bivalent cations, such as magnesium (Mg) or manganese (Mn) ions, and monovalent cations such as potassium (K) ions.
[0020] As used herein, a microreaction chamber refers to or includes an enclosed structure for performing a chemical reaction. The microreaction chamber may have dimensions ranging from approximately 5 pm width x 5 pm length x 5 pm depth to about 1 millimeter (mm) width x 1 mm length x 1 mm depth. Examples are not limited to microreaction chambers having a same width, length, and depth, and each of the measurements may be different. In some examples, the microreaction chamber has dimensions of approximately 20 urn x 20 urn x 20 urn. Also, while the microreaction chamber is illustrated herein as generally straight, examples are not so limited and the microreaction chamber may have a serpentine shape, a chevron shape, among other formations.
[0021] At 102, the method 100 includes placing a microreaction chamber 101 into an oscillating magnetic field. As discussed further herein, a plurality of magnetic particles may be embedded in a layer 105 on the surface of the microreaction chamber101 . Referring to FIG. 1 , the plurality of magnetic particles embedded in the microreaction chamber 101 include a plurality of magnetic particles of a first type, and a plurality of magnetic particles of a second type. The first type of magnetic particles may have a first Curie temperature corresponding with a temperature of a temperature-sensitive reaction, and a first resonance frequency at which the magnetic particles respond to the oscillating magnetic field 103. The plurality of magnetic particles further include a plurality of magnetic particles of a second type, wherein the second type of magnetic particles have a second Curie temperature corresponding with a temperature of the temperature-sensitive reaction, and a second resonance frequency at which the magnetic particles respond to the oscillating magnetic field 103. [0022] As used herein, a Curie temperature refers to or includes a temperature above which certain materials lose their permanent magnetic properties, which can be replaced by induced magnetism. When exposed to an oscillating magnetic field, the plurality of magnetic particles heat up, through hysteresis losses, until they reach their Curie temperature. At the Curie temperature (e.g., Curie point) for each type of magnetic particle, heat generation through hysteresis loss ceases and the particles stop heating the solution within the microreaction chamber. The Curie temperature is a property of the material comprising the magnetic particles, and relative proportions of materials (as appropriate). For instance, in some examples, the plurality of magnetic particles consist essentially of iron oxide, a soft ferrite, a ferromagnetic material, a ferrimagnetic material, or combinations thereof. Non-limiting example compositions of magnetic particles include iron oxide (Fe2Os), soft ferrites ranging from spinel-type ferrites (MeFe2C>4) to manganese-zinc ferrite (MnaZn(i-a)Fe2O4), nickel-zinc ferrite (NiaZn(i-a)Fe2O4), and a nickel-iron alloy (Ni-Fe (80:20)), among others. In various examples, the value of ‘a’ may be selected to change the particular alloy to have a particular Curie temperature. [0023] Moreover, when placed in an electromagnetic field, the hysteresis losses in the magnetic particles cause the temperature of the magnetic particles to rise, eventually reaching the Curie temperature for the magnetic particle. Upon reaching the Curie temperature, the material crystal lattice undergoes a dimensional change, causing a reversible loss of magnetic dipoles. Once the magnetic dipoles are lost, the ferromagnetic properties cease, thus halting further heating. Each of the magnetic particles have a range of resonance frequencies at which the magnetic particles lose heat by hysteresis.
Accordingly, magnetic particles with a different material composition and different Curie temperature, may heat the solution within the microreaction chamber 101 to different respective temperatures.
[0024] The oscillating magnetic field is illustrated in FIG. 1 by 103-a and 103-b. Particularly, 103-a illustrates magnetic field lines going into the page, whereas 103-b illustrates magnetic field lines coming out of the page. The oscillating magnetic field may be formed using an electromagnetic field (EMF) generator. Although FIG. 1 illustrates the oscillating magnetic field extending perpendicular to the microreaction chamber 101 , examples are not so limited. The oscillating magnetic field may also be referred to as oscillating magnetic field 103.
[0025] At 104, the method 100 includes heating a solution 107 inside the microreaction chamber to a particular temperature associated with the plurality of magnetic particles by maintaining the oscillating magnetic field at a resonance frequency selected from the first resonance frequency and the second resonance frequency. For instance, at 109, the solution 107 may be heated to a particular temperature by maintaining the oscillating magnetic field 103 at a resonance frequency corresponding with the first magnetic particles and/or the second magnetic particles. Accordingly, in various examples, heating the solution to the first Curie temperature includes heating the first type of magnetic particles to the first Curie temperature, and heating the solution to the second Curie temperature includes heating the second type of magnetic particles to the second Curie temperature. As discussed further herein, the type of magnetic particles may be selected for their specific Curie temperatures, such that the Curie temperatures align with a particular target temperature of a temperature-sensitive reaction. In various examples, the plurality of magnetic particles include a first type of magnetic particles having a first Curie temperature at a first target temperature for the microreaction chamber and a second type of magnetic particles having a second Curie temperature at a second target temperature for the microreaction chamber.
[0026] As an illustration, method 100 may be used to carry out PCR, among other temperature-sensitive reactions. In PCR, short sense and antisense oligonucleotides, which delimit the region to be amplified, are added to the solution 107 with the template in a low concentration, a thermostable polymerase and individual nucleotides. The solution may be heated to approximately 95-100° C by exposing the microreaction chamber to an oscillating magnetic field 103 with a first frequency, thereby heating a first type of magnetic particles in the layer 105 to a first Curie temperature. The solution may further by heated to approximately 40-65° C by exposing the microreaction chamber to an oscillating magnetic field 103 with a second frequency, thereby heating a second type of magnetic particles in the layer 105 to a second Curie temperature. As a further illustration, the solution may be heated to approximately 70-80° C by exposing the microreaction chamber to an oscillating magnetic field 103 with a third frequency, thereby heating a third type of magnetic particles in the layer 105 to a third Curie temperature.
[0027] In some examples, the solution 107 inside the microreaction chamber 101 may be heated to a plurality of different temperatures by altering the resonance frequency of the oscillating magnetic field 103. In such examples, heating the solution inside the microreaction chamber includes heating the solution to a first temperature associated with the first type of magnetic particles by applying a first resonance frequency to the oscillating magnetic field, and heating the solution to a second temperature associated with the second type of magnetic particles by applying a second resonance frequency to the oscillating magnetic field. For instance, heating the solution to the first temperature includes heating the first type of magnetic particles to a Curie temperature of the first type of magnetic particles, and heating the solution to the second temperature includes heating the second type of magnetic particles to a Curie temperature of the second type of magnetic particles.
[0028] In various examples, the method 100 includes selectively activating the first type of magnetic particles or the second type of magnetic particles by changing the resonance frequency of the oscillating magnetic field. For instance, by changing a frequency of the oscillating magnetic field 103, a different respective magnetic particle type may be activated, and a different respective Curie temperature may be achieved.
[0029] In various examples, the first Curie temperature and the second Curie temperature are below a melting point of the surface of the microreaction chamber. By having a Curie temperature below the melting point of the surface of the microreaction chamber 101 , the magnetic particles heat the solution 107 by induction without melting the walls of the microreaction chamber 101. In such examples, heating the solution inside the microreaction chamber includes heating the solution to the first temperature associated with the first type of magnetic particles by applying the first resonance frequency to the oscillating magnetic field 103, and heating the solution 107 to the second temperature associated with the second type of magnetic particles by applying the second resonance frequency to the oscillating magnetic field 103.
[0030] By heating the solution 107 inside the microreaction chamber 101 with magnetic particles embedded in a layer 105 of the microreaction chamber, uniform heating and temperature control with minimal temperature gradients may be achieved. As discussed further herein, the magnetic particles may be embedded in various surfaces of the microreaction chamber, and may also be embedded into structural elements of the microreaction chamber to locally control temperature. As an illustration, heating pillars may be used to elute nucleic acid material bound to them, to denature bound proteins, lyse cells, and/or to deactivate a bound virus.
[0031] FIG. 2 illustrates an example apparatus for heating a solution inside a microreaction chamber, in accordance with the present disclosure. As illustrated in FIG. 2, apparatus 209 includes a base substrate 211 extending along a first planar surface (e.g., extending along the x-plane), and a top wall 217 extending along a second planar surface generally parallel to the first planar surface. The apparatus 209 further includes a first side wall 215 extending along a third planar surface (e.g., extending along the y-plane) generally perpendicular to the first planar surface and second planar surface, and a second side wall 213 extending generally parallel to the third planar surface. The base substrate 211 , the top wall 217, the first side wall 215, and the second side wall 213 form a microreaction chamber 201 . As discussed with regards to FIG. 2, a polymeric layer 205 may be disposed on the first planar surface, the second planar surface, the third planar surface, or the fourth planar surface, wherein the polymeric layer 205 includes a plurality of magnetic particles 219 having a Curie temperature at a target temperature for the microreaction chamber. Although FIG. 2 illustrates the polymeric layer 205 being disposed along the first side wall 215, examples are not so limited. The polymeric layer 205 may be disposed on side wall 215, side wall 213, base substrate 211 , top wall 217, or various combinations thereof. Exploded view 212 illustrates the polymeric layer 205 disposed on side wall 215, and exposed to the solution 207 inside microreaction chamber 201 .
[0032] As used herein, a polymeric layer refers to or includes a polymeric matrix that contains a plurality of magnetic particles. The polymeric matrix may comprise natural or synthetic polymer matrices. Non-limiting examples of natural polymers include polysaccharides such as dextran, sepharose, polypeptides such as poly-L-aspartate, poly-L-glutamate, polylactides such as poly-P, L- lactide. Non-limiting examples of synthetic polymer matrices include polyvinyl alcohol, polystyrene (derivatives), poly(meth)acrylates and -acrylamides, polypyrroles, polyesters, poly-s-caprolactam, etc. and copolymers also with natural polymers.
[0033] In various examples, the magnetic particles are of a size and concentration to keep the polymeric layer 205 transparent for photolithography. As non-limiting examples, the magnetic particles have a diameter of between approximately 50 pm to approximately 5 nanometers (nm). In some examples, a concentration of magnetic particles in the polymeric layer ranges from approximately 1% by weight to approximately 10% per weight.
[0034] As discussed with regards to FIG. 1 , the polymeric layer 205 may include a plurality of embedded magnetic particles. The polymeric layer 205 may include a first type 219-1 of magnetic particles having a first Curie temperature at a first target temperature for the microreaction chamber and a second type 219-2 of magnetic particles having a second Curie temperature at a second target temperature for the microreaction chamber. For instance, the first type 219-1 of magnetic particles may have a Curie temperature for a first temperature of a temperature-sensitive reaction, whereas the second type 219- 2 of magnetic particles may have a Curie temperature for a second temperature of the temperature-sensitive reaction. In various examples, the polymeric layer 205 is semitransparent, enabling optical interrogation of the solution 207 inside the microreaction chamber.
[0035] FIG. 3. Illustrates an example apparatus including a microreaction chamber having a multi-walled polymeric layer, in accordance with the present disclosure. More particularly, FIG. 3 illustrates an example microreaction chamber wherein the polymeric layer is disposed on the first planar surface, the second planar surface, and the third planar surface. The apparatus 309 illustrated in FIG. 3 includes similar components as apparatus 209 illustrated in FIG. 2. For instance, apparatus 309 includes a base substrate 311 similar to base substrate 21 1 illustrated in FIG. 2, a first side wall 315 similar to side wall 215 illustrated in FIG. 2, a second side wall 313 similar to side wall 213 illustrated in FIG. 2, and a top wall 317 similar to top wall 217 illustrated in FIG.
2. As illustrated in FIG. 3, the microreaction chamber 301 may store the solution for the temperature-sensitive reaction. Moreover, the polymeric layer 305 may be deposited on a plurality of walls lining the microreaction chamber 301 . For instance, the polymeric layer 305 may be disposed on the first planar surface, the second planar surface, and the third planar surface. In such an arrangement, optical performance may be improved by having one wall (e.g., top wall 317) not have a semitransparent polymeric layer. Examples are not limited to the particular arrangement illustrated in FIG. 3, and in some examples the polymeric layer 305 is disposed on the base substrate 311 , the top wall 317, the first side wall 315, and the second side wall 313 of the microreaction chamber.
[0036] FIG. 4, illustrates an example apparatus including a microreaction chamber having a polymeric layer on all surfaces inside the microreaction chamber, in accordance with the present disclosure. The apparatus 409 illustrated in FIG. 4 includes similar components as apparatus 309 illustrated in FIG. 3. For instance, apparatus 409 includes a base substrate 411 similar to base substrate 31 1 illustrated in FIG. 3, a first side wall 415 similar to side wall 315 illustrated in FIG. 3, a second side wall 413 similar to side wall 313 illustrated in FIG. 3, and a top wall 417 similar to top wall 317 illustrated in FIG.
3. As illustrated in FIG. 4, the microreaction chamber 401 may store the solution for the temperature-sensitive reaction. Moreover, the polymeric layer 405 may be deposited on all four walls lining the microreaction chamber 301 . For instance, the polymeric layer 305 may be disposed on the first planar surface, the second planar surface, the third planar surface, and the fourth planar surface. [0037] FIGs. 5A, 5B, and 50 illustrate various example designs of an apparatus including a microreaction chamber having a polymeric layer, in accordance with the present disclosure. FIG. 5A illustrates apparatus 506, FIG. 5B illustrates apparatus 508, and FIG. 50 illustrates apparatus 510. Each of the apparatuses may be formed by the following process. Magnetic particles may be mixed with a polymer resist to disperse the particles into the polymer resist, and the magnetic polymer resist may be spin coated onto substrate to form the polymeric layer described herein. The resultant layers include the base substrate 511 and polymeric layer 505-a. The resultant material is baked. In various examples, such as apparatus 508 and apparatus 510 an etch stop layer may be deposited onto the base substrate 511. The etch stop layer may be an evaporated or sputtered thin metal layer. Another layer of magnetic polymer resist may be spin coat to form polymeric layer 505-b. Apparatus 508 and apparatus 510 may be exposed to lithographically to define the edges of polymeric layers 505-a and 505-b.
[0038] As a further example, apparatus 506, apparatus 508, and apparatus 510 may be formed by depositing polymeric layer 505-a by spin-coating or thin film deposition onto base substrate 511. In some examples, magnetic material is patterned onto layer 505-a by photolithography or an etch process. The microfluidic chamber layer may be deposited on the polymeric layer 505-a by spin coating or thin film deposition of side wall 515 and side wall 513. A second polymeric layer 505-b may be deposited by spin-coating, thin film deposition or hot air lamination method. The second magnetic material may be patterned using a photolithography or etch process. In some examples, an additional top hat layer 517 may be laminated to increase structural strength of the top hat. [0039] Following this process, the apparatus 506 includes two continuous polymeric layers 505-a and 505-b extending a width of the apparatus 506. In the example illustrated in FIG. 5B, the apparatus 508 includes one of the polymeric layers patterned, while the other of the two polymeric layers extends the width of the apparatus. While FIG. 5B illustrates polymeric layer 505-a patterned and polymeric layer 505-b extending a width of the apparatus, examples are not so limited, and polymeric layer 505-b may extend a length of the apparatus while polymeric layer 505-a is patterned. In the example illustrated in FIG. 50, both polymeric layer 505-a and polymeric layer 505-b are patterned.
[0040] FIG. 6 illustrates an example apparatus 609 including a plurality of longitudinal ridges, in accordance with the present disclosure. The apparatus 609 illustrated in FIG. 6 includes similar components as apparatus 209 illustrated in FIG. 2. For instance, apparatus 609 includes a base substrate 61 1 similar to base substrate 21 1 illustrated in FIG. 2, a first side wall 615 similar to side wall 215 illustrated in FIG. 2, a second side wall 613 similar to side wall 213 illustrated in FIG. 2, and a top wall 617 similar to top wall 217 illustrated in FIG.
2. Combined, walls 615, 617, 611 , and 613 define a microreaction chamber 601.
[0041] As illustrated by FIG. 6, the polymeric layer may be deposited on a plurality of longitudinal ridges 621 -1 , 621 -2, 621 -3, and 621 -4 (collectively referred to herein as longitudinal ridges 621 ). The longitudinal ridges 621 may extend from the base substrate 61 1 toward the top wall 617, and may comprise the polymeric layer described herein. In some examples, the longitudinal ridges 621 may comprise ridges coated in the polymeric layer. In some examples, the longitudinal ridges 621 may comprise essentially of the polymeric layer.
Although FIG. 6 illustrates the longitudinal ridges 621 extending from the base substrate 611 to the top wall 617, examples are not so limited. For instance, the longitudinal ridges 621 may comprise ribbons of the polymeric layer that are deposited along the base substrate 611 in strips. Accordingly, various apparatuses described herein may include a plurality of longitudinal ridges extending a length of the apparatus along a plane generally parallel to the microreaction chamber, wherein the polymeric layer is embedded in a surface of the plurality of longitudinal ridges.
[0042] FIG. 7 illustrates an example apparatus including a plurality of cooling chambers, in accordance with the present disclosure. The apparatus 709, may include a microreaction chamber 701 extending a length of the apparatus. In various examples, the microreaction chamber 701 includes a base substrate 71 1 , a top wall 717 extending generally parallel to the base substrate 711 , and first side wall 723 extending generally perpendicular to the base substrate 71 1 and the top wall 717. The microreaction chamber 701 further includes a second side wall 721 extending generally parallel to the first side wall 723. As illustrated, side wall 713 may extend generally parallel to side wall 721 , and side wall 715 may extend generally parallel to side wall 723.
[0043] As discussed herein, the apparatus 709 may include a polymeric layer 705 disposed on a surface of the microreaction chamber 701 , wherein the polymeric layer includes a plurality of magnetic particles having a Curie temperature at a target temperature for the microreaction chamber. Additionally, the apparatus 709 may include a cooling chamber extending the length of the apparatus and generally parallel to the microreaction chamber 701 . The example in FIG. 7 illustrates two cooling chambers 719 and 720 that extend the length of the apparatus and are generally parallel to the microreaction chamber 701 . As discussed herein, the microreaction chamber 701 may contain a solution 707 for a temperature-sensitive reaction. Cooling chambers 719 and 720 may include a sink that is capable of absorbing heat from the microreaction chamber 701 . A non-limiting example of a sink that may be included in the cooling chambers 719 and 720 is water. The cooling chamber may also include added materials that help identify a relative temperature of the cooling chamber. For instance, in some examples, the cooling chamber includes a volume of a liquid including a temperature sensitive dye. The temperature sensitive dye may change colors when the temperature of the solution in the cooling chamber reaches a threshold temperature. Additionally, in various examples, the base substrate, the top wall, the first side wall, or the second side wall include a region of semi-transparent material for optical interrogation of the microreaction chamber.
[0044] Although FIG. 7 illustrates the polymeric layer 705 disposed on the inner surface of the microreaction chamber 701 , examples are not so limited. For instance, the polymeric layer 705 may be arranged in various manners as discussed and illustrated in the foregoing examples. For instance, in some examples, the apparatus 709 includes a plurality of longitudinal ridges extending a length of the apparatus along a plane generally parallel to the microreaction chamber, wherein the polymeric layer is embedded in a surface of the plurality of longitudinal ridges.
[0045] As illustrated in FIG. 7, the polymeric layer 705 may be disposed on the base substrate, the top wall, the first side wall, and the second side wall of the microreaction chamber. However, examples are not so limited. In some examples, the polymeric layer 705 may be disposed on side walls 723 and 721 , as well as base substrate 71 1 , among other non-limiting examples.
[0046] FIG. 8 illustrates an example apparatus including a plurality of cooling chambers, in accordance with the present disclosure. As illustrated in FIG. 8, the apparatus 809 may include additional cooling chambers, as compared to the example illustrated in FIG. 7. For instance, the apparatus 809, may include a microreaction chamber 801 extending a length of the apparatus. In various examples, the microreaction chamber 801 includes a base substrate 811 , a top wall 817 extending generally parallel to the base substrate 811 , and first side wall 823 extending generally perpendicular to the base substrate 811 and the top wall 817. The microreaction chamber 801 further includes a second side wall 821 extending generally parallel to the first side wall 823. As illustrated, side wall 813 may extend generally parallel to side wall 821 , and side wall 815 may extend generally parallel to side wall 823.
[0047] As discussed herein, the apparatus 809 may include a polymeric layer 805 disposed on a surface of the microreaction chamber 801 , wherein the polymeric layer includes a plurality of magnetic particles having a Curie temperature at a target temperature for the microreaction chamber. Additionally, the apparatus 809 may include a cooling chamber extending the length of the apparatus and generally parallel to the microreaction chamber 801 .
[0048] The example in FIG. 8 illustrates cooling chambers 819, 820, 825 and 827 that extend the length of the apparatus and are generally parallel to the microreaction chamber 801 . A top wall 829 may separate the cooling chamber 827 from the microreaction chamber 801 and the cooling chambers 819 and 820. Similarly, a base substrate 831 may separate the cooling chamber 825 from the microreaction chamber 801 and the cooling chambers 819 and 820. [0049] As discussed with regards to FIG. 7, the microreaction chamber 801 may contain a solution 807 for a temperature-sensitive reaction. Cooling chambers 819, 820, 825, and/or 827 may include a sink that is capable of absorbing heat from the microreaction chamber 801 . A non-limiting example of a sink that may be included in the cooling chambers is water. The cooling chamber may also include added materials that help identify a relative temperature of the cooling chamber. For instance, in some examples, the cooling chamber includes a volume of a liquid including a temperature sensitive dye. The temperature sensitive dye may change colors when the temperature of the solution in the cooling chamber reaches a threshold temperature. Additionally, in various examples, the base substrate, the top wall, the first side wall, or the second side wall include a region of semi-transparent material for optical interrogation of the microreaction chamber.
[0050] Although specific examples have been illustrated and described herein, a variety of alternate and/or equivalent implementations may be substituted for the specific examples shown and described without departing from the scope of the present disclosure. This application is intended to cover any adaptations or variations of the specific examples discussed herein.

Claims

1 . A method comprising: placing a microreaction chamber into an oscillating magnetic field, wherein a plurality of magnetic particles are embedded on a surface of the microreaction chamber, the plurality of magnetic particles including: a plurality of magnetic particles of a first type, wherein the first type of magnetic particles have a first Curie temperature corresponding with a temperature of a temperature-sensitive reaction, and a first resonance frequency at which the magnetic particles respond to an oscillating magnetic field; and a plurality of magnetic particles of a second type, wherein the second type of magnetic particles have a second Curie temperature corresponding with a temperature of the temperature-sensitive reaction, and a second resonance frequency at which the magnetic particles respond to the oscillating magnetic field; and heating a solution inside the microreaction chamber to a particular temperature associated with the plurality of magnetic particles by maintaining the oscillating magnetic field at a resonance frequency selected from the first resonance frequency and the second resonance frequency.
2. The method of claim 1 , wherein the first Curie temperature and the second Curie temperature are below a melting point of the surface of the microreaction chamber.
3. The method of claim 2, wherein heating the solution to the first Curie temperature includes heating the first type of magnetic particles to the first Curie temperature, and heating the solution to the second Curie temperature includes heating the second type of magnetic particles to the second Curie temperature.
4. The method of claim 2, including selectively activating the first type of magnetic particles or the second type of magnetic particles by changing the resonance frequency of the oscillating magnetic field.
5. An apparatus, comprising: a base substrate extending along a first planar surface, and a top wall extending along a second planar surface generally parallel to the first planar surface; a first side wall extending along a third planar surface generally perpendicular to the first planar surface and second planar surface, and a second side wall extending along a fourth planar surface generally parallel to the third planar surface, wherein the base substrate, the top wall, the first side wall, and the second side wall form a microreaction chamber; and a polymeric layer disposed on the first planar surface, the second planar surface, the third planar surface, or the fourth planar surface, wherein the polymeric layer includes a plurality of magnetic particles having a Curie temperature at a target temperature for the microreaction chamber.
6. The apparatus of claim 5, wherein the polymeric layer is disposed on the first planar surface, the second planar surface, and the third planar surface.
7. The apparatus of claim 5, wherein the magnetic particles have a diameter of between approximately 50pm to approximately 5 nm.
8. The apparatus of claim 5, wherein a concentration of magnetic particles in the polymeric layer ranges from approximately 1% by weight to approximately 10% per weight.
9. The apparatus of claim 5, wherein the plurality of magnetic particles include a first type of magnetic particles having a first Curie temperature at a first target temperature for the microreaction chamber and a second type of magnetic particles having a second Curie temperature at a second target temperature for the microreaction chamber.
10. The apparatus of claim 5, wherein the plurality of magnetic particles consist essentially of iron oxide, a soft ferrite, a ferromagnetic material, a ferrimagnetic material, or combinations thereof.
11. An apparatus, comprising: a microreaction chamber extending a length of the apparatus, the microreaction chamber including: a base substrate; a top wall extending generally parallel to the base substrate; a first side wall extending generally perpendicular to the base substrate and the top wall; and a second side wall extending generally parallel to the first side wall; a polymeric layer disposed on a surface of the microreaction chamber, wherein the polymeric layer includes a plurality of magnetic particles having a Curie temperature at a target temperature for the microreaction chamber; and a cooling chamber extending the length of the apparatus and generally parallel to the microreaction chamber.
12. The apparatus of claim 11 , further including a plurality of longitudinal ridges extending a length of the apparatus along a plane generally parallel to the microreaction chamber, wherein the polymeric layer is embedded in a surface of the plurality of longitudinal ridges.
13. The apparatus of claim 11 , wherein the polymeric layer is disposed on the base substrate, the top wall, the first side wall, and the second side wall of the microreaction chamber. 21
14. The apparatus of claim 11 , wherein the cooling chamber includes a volume of a liquid including a temperature sensitive dye.
15. The apparatus of claim 11 , wherein the base substrate, the top wall, the first side wall, or the second side wall include a region of semi-transparent material for optical interrogation of the microreaction chamber.
PCT/US2020/055278 2020-10-12 2020-10-12 Heating a solution inside a microreaction chamber with embedded magnetic particles WO2022081132A1 (en)

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Citations (5)

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EP0696156A1 (en) * 1990-01-16 1996-02-07 Metcal, Inc. Magnetic particles
WO2007134061A2 (en) * 2006-05-09 2007-11-22 Thermal Solutions, Inc. Magnetic element temperature sensors
EP2021751B1 (en) * 2006-05-09 2018-03-21 TSI Technologies LLC Magnetic element temperature sensors
US20180117186A1 (en) * 2016-11-01 2018-05-03 The Regents Of The University Of Colorado, A Body Corporate Magnetic particles for use in magnetic resonance imaging thermometry
US20200290003A1 (en) * 2016-04-26 2020-09-17 Haldor Topsøe A/S Induction heated aromatization of higher hydrocarbons

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0696156A1 (en) * 1990-01-16 1996-02-07 Metcal, Inc. Magnetic particles
WO2007134061A2 (en) * 2006-05-09 2007-11-22 Thermal Solutions, Inc. Magnetic element temperature sensors
EP2021751B1 (en) * 2006-05-09 2018-03-21 TSI Technologies LLC Magnetic element temperature sensors
US20200290003A1 (en) * 2016-04-26 2020-09-17 Haldor Topsøe A/S Induction heated aromatization of higher hydrocarbons
US20180117186A1 (en) * 2016-11-01 2018-05-03 The Regents Of The University Of Colorado, A Body Corporate Magnetic particles for use in magnetic resonance imaging thermometry

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