WO2022081131A1

WO2022081131A1 - Magnetic particles to heat a solution via an oscillating magnetic field

Info

Publication number: WO2022081131A1
Application number: PCT/US2020/055277
Authority: WO
Inventors: Viktor Shkolnikov; Alexander Govyadinov
Original assignee: Hewlett-Packard Development Company, L.P.
Priority date: 2020-10-12
Filing date: 2020-10-12
Publication date: 2022-04-21

Abstract

A method comprising placing a microreaction chamber, including a solution for a temperature- sensitive reaction, into an oscillating magnetic field, and heating the solution inside the microreaction chamber to a particular temperature by maintaining the oscillating magnetic field at a resonance frequency selected from the first resonance frequency and the second resonance frequency. The solution includes a plurality of magnetic particles of a first type and a plurality of magnetic particles of a second type, wherein the first type of magnetic particles have a first Curie temperature and the second type of magnetic particles have a second Curie temperature respectively, corresponding with a temperature of a temperature- sensitive reaction, and a first resonance frequency and a second resonance frequency respectively, at which the magnetic particles respond to an oscillating magnetic field.

Description

MAGNETIC PARTICLES TO HEAT A SOLUTION VIA AN OSCILLATING MAGNETIC FIELD

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 a composition for heating a solution for a temperaturesensitive reaction, in accordance with the present disclosure.

[0004] FIG. 3 illustrates an example composition including a plurality of polymeric particles, in accordance with the present disclosure. [0005] FIG. 4 illustrates an example composition including a plurality of polymeric particles, each including a primer for a temperature-sensitive reaction, in accordance with the present disclosure.

[0006] FIG. 5 illustrates an example composition including a plurality of polymeric particles, each including an enzyme for a temperature-sensitive reaction, in accordance with the present disclosure.

[0007] FIG. 6 illustrates an apparatus for heating a solution for a temperaturesensitive reaction, in accordance with the present disclosure.

[0008] FIG. 7 illustrates a block diagram of an example method for heating a solution for a temperature-sensitive reaction, in accordance with the present disclosure.

[0009] FIG. 8 illustrates a block diagram of an example method for heating a solution for a temperature-sensitive reaction, 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 (PCR), 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, 2" 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 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 for a temperature-sensitive reaction via an oscillating magnetic field includes placing a microreaction chamber into an oscillating magnetic field, wherein the microreaction chamber encloses a solution for a temperature-sensitive reaction, and heating the 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. The solution includes 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 solution further includes 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.

[0017] As another example, a composition for heating a solution for a temperature-sensitive reaction includes a solution for a temperature-sensitive reaction, and 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 the temperature-sensitive reaction, and a first resonance frequency at which the magnetic particles respond to an oscillating magnetic field. Additionally, the composition includes 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 temperaturesensitive reaction, and a second resonance frequency at which the magnetic particles respond to the oscillating magnetic field.

[0018] As a further example, an apparatus for heating a solution for a temperature-sensitive reaction includes a microreaction chamber extending a length of the apparatus, and a solution for a temperature-sensitive reaction enclosed within the microreaction chamber. In some examples, the solution includes 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 the temperature-sensitive reaction, and a first resonance frequency at which the magnetic particles respond to an oscillating magnetic field.

[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] At 101 , the method 100 includes placing a microreaction chamber into an oscillating magnetic field, wherein the microreaction chamber encloses a solution for a temperature-sensitive reaction. Referring to FIG. 1 , microreaction chamber 103 includes a solution 105. As discussed more thoroughly with regards to FIG. 2, the solution 105 may include a plurality of magnetic particles. As an example, the solution may 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.

[0021] 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 (MeFe2O4) to manganese-zinc ferrite (Mn_aZn(i-a)Fe2O4), nickel-zinc ferrite (Ni_aZn(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. As non-limiting examples, the magnetic particles have a diameter of between approximately 50 micrometers (pm) to approximately 5 nanometers (nm). [0022] 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.

[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 solution further includes 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 oscillating magnetic field is illustrated in FIG. 1 by 107-a and 107-b. Particularly, 107-a illustrates magnetic field lines going into the page, whereas 107-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 102, examples are not so limited. The oscillating magnetic field may also be referred to as oscillating magnetic field 107.

[0025] At 109, the method 100 includes heating the 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. For instance, at 109, the solution 105 may be heated to a particular temperature by maintaining the oscillating magnetic field 107 at a resonance frequency corresponding with the first magnetic particles and/or the second magnetic particles.

[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 105 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 107 with a first frequency, thereby heating a first type of magnetic particles in the microreaction chamber 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 107 with a second frequency, thereby heating a second type of magnetic particles in the microreaction chamber 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 107 with a third frequency, thereby heating a third type of magnetic particles in the microreaction chamber to a third Curie temperature.

[0027] In some examples, the solution 105 inside the microreaction chamber 103 may be heated to a plurality of different temperatures by altering the resonance frequency of the oscillating magnetic field 107. 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] Examples of the present disclosure allow for a plurality of different types of magnetic particles to be mixed into the solution 105 to achieve a plurality of different temperatures of the temperature-sensitive reaction. As such, n-different types of magnetic particles may be included in the solution within the microreaction chamber. The particles may be mixed with the solution 105 and occupy the volume of the microreaction chamber. Each type of the particles has a Curie temperature associated with a particular temperature to be achieved by the microreaction chamber, as well as a resonance frequency at which it responds to the oscillating magnetic field. Outside of the channel may be an induction heating system, including a coil which produces an oscillating magnetic field 107 at frequencies associated with the resonance frequencies of the particles. During operation, the induction heating system may produce a magnetic field at a frequency A associated with type / particles. This oscillating magnetic field heats the particles, and the heat conducts into the rest of the solution, heating the solution to the temperature of the particles. Because of resonance, type / particles respond to frequency Awhile the other particles do not heat at this frequency. The particles increase in temperature until they reach their Curie temperature, at which point the particles stop responding to the magnetic field frequency and stop heating. To reach a different temperature, a different frequency is applied, which actuates a different particle type, with a different Curie temperature. Accordingly, 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. [0029] FIG. 2 illustrates a composition 21 1 for heating a solution for a temperature-sensitive reaction, in accordance with the present disclosure. In the example illustrated in FIG. 2, the composition 211 may comprise a solution for a temperature-sensitive reaction, and 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 the temperature-sensitive reaction, and a first resonance frequency at which the magnetic particles respond to an oscillating magnetic field. Additionally, the composition includes 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. For instance, referring to FIG. 2, a plurality of magnetic particles 213-1 , 213-2, ...213-n (collectively referred to herein as magnetic particles 213) may be of a first type, and a plurality of magnetic particles 215-1 , 215-2, ...215-m (collectively referred to herein as magnetic particles 215) may be of a second type. While FIG. 1 illustrates two types of magnetic particles (e.g., magnetic particles 213 and magnetic particles 215) in composition 21 1 , examples are not so limited, and a single type of magnetic particle may be present in composition 211 , and/or more than two different types of magnetic particles may be present in composition 21 1.

[0030] As used herein, a different type of magnetic particle refers to or includes a magnetic particle with a Curie temperature and/or a resonance frequency that differs from another type of magnetic particle. In some examples, magnetic particles may have a same Curie temperature but a different respective resonance frequency. Moreover, magnetic particles may have a same resonance frequency but a different respective Curie temperature.

[0031] The magnetic particles 213 and 215 may allow for precise temperature control of a microfluidic chamber with minimal temperature gradients, without temperature sensing and feedback control, and therefore in a low cost manner. The magnetic particles 213 and 1215 may be mixed with a solution 205. Each type of the particles has a Curie temperature associated with the desired temperature of the chamber, as well as a resonance frequency at which it responds to the oscillating magnetic field. As described herein, the magnetic particles 213, and 215 may be used as an inductive heating element with controlled alternating current frequency heating such that specific types of particles reach their Curie temperature. At this point particles stop responding to the magnetic field frequency and stop heating. This thus limits their temperature to their Curie temperature. To reach a different temperature, a different frequency may be applied, which actuates a different particle type, with a different Curie temperature. This enables precision thermocycling without us of a feedback control system. As discussed with regards to FIG. 3, the composition may include a plurality of polymeric particles, wherein each of the polymeric particles includes a polymeric matrix, a sub-part of the plurality of magnetic particles of the first type, and a sub-part of the plurality of magnetic particles of the second type.

[0032] FIG. 3 illustrates an example composition 31 1 including a plurality of polymeric particles 317-1 , 317-2, 317-n (referred to collectively as “polymeric particles 317”), in accordance with the present disclosure. Each of the polymeric particles 317 may include a polymeric matrix, a sub-part of the plurality of magnetic particles of the first type, and a sub-part of the plurality of magnetic particles of the second type. For instance, polymeric particle 317-1 may include a magnetic particle 313-1 of a first type, a magnetic particle 315-1 of a second type, a magnetic particle 319-1 of a third type, and a magnetic particle 321 -1 of a fourth type. Similarly, polymeric particle 317-2 may include a magnetic particle 313-2 of a first type, a magnetic particle 315-2 of a second type, a magnetic particle 319-2 of a third type, and a magnetic particle 321 -2 of a fourth type. Moreover, polymeric particle 317-n may include a magnetic particle 313-n of a first type, a magnetic particle 315-n of a second type, a magnetic particle 319-n of a third type, and a magnetic particle 321 -n of a fourth type.

[0033] While FIG. 3 illustrates a single magnetic particle of each type, examples are not so limited. For instance, a plurality of magnetic particles of the first type, a plurality of magnetic particles of the second type, a plurality of magnetic particles of the third type, and a plurality of magnetic particles of the fourth type, may be included in each of polymeric particles 317-1 , 317-2, and 317-n. Moreover, more or fewer types of magnetic particles may be included in each polymeric particle. For instance, polymeric particle 317-1 may include a plurality of magnetic particles 313-1. As another illustration, polymeric particle 317-1 may include a plurality of magnetic particles 313-1 , and a plurality of magnetic particles 315-1 . Yet further, polymeric particle 317-1 may include a plurality of magnetic particles 313-1 , a plurality of magnetic particles 315-1 , and a plurality of magnetic particles 319-1 .

[0034] In some examples, each polymeric particle of the plurality of polymeric particles 317 may include an unequal distribution of different types of magnetic particles. For instance, polymeric particles 317-1 , 317-2 and 317-n may include a first number of magnetic particles of a first type (e.g., 313-1 , 313-2, and 313-n) a second number of magnetic particles of the second type (e.g., 315-1 , 315-2, 315-n), where the first number is different than the second number. Yet further, polymeric particles 317-1 , 317-2 and 317-n may include a first number of magnetic particles of a first type (e.g., 313-1 , 313-2, and 313-n) a second number of magnetic particles of the second type (e.g., 315-1 , 315-2, 315-n), where the first number is different than the second number, and a third number of magnetic particles of a third type (e.g., 319-1 , 319-2, 319-n), where the first number, second number, and the third number are different numbers.

[0035] Each of the polymeric particles 317 may comprise natural (e.g. polysaccharides such as dextran, sepharose, polypeptides such as poly-L- aspartate, poly-L-glutamate, polylactides such as poly-P, L-lactide) or synthetic polymer matrices (e.g. polyvinyl alcohol, polystyrene (derivatives), poly(meth)acrylates and -acrylamides, polypyrroles, polyesters, poly-s- caprolactam, etc. and copolymers also with natural polymers).

[0036] As described herein, each of the plurality of magnetic particles may have a different Curie temperature so that a plurality of different temperatures may be achieved using the magnetic particles. For instance, magnetic particles of the first type (e.g., 313-1 , 313-2, and 313-n) may have a first Curie temperature, while magnetic particles of the second type (e.g., 315-1 , 315-2, and 315-n) may have a second Curie temperature, magnetic particles of the third type (e.g., 319- 1 , 319-2, and 319-n) may have a third Curie temperature, and magnetic particles of the fourth type (e.g., 321 -1 , 321 -2, and 321 -n) may have a fourth Curie temperature. Magnetic particles of the first type (e.g., 313-1 , 313-2, and 313-n) are referred to collectively as “magnetic particles of the first type 313”, magnetic particles of the second type (e.g., 315-1 , 315-2, and 315-n) are referred to collectively as “magnetic particles of the second type 315”. Magnetic particles of the third type (e.g., 319-1 , 319-2, and 319-n) are referred to collectively as “magnetic particles of the third type 319”, and magnetic particles of the fourth type (e.g., 321 -1 , 321 -2, and 321 -n) are referred to collectively as “magnetic particles of the fourth type 321 .”

[0037] Each of the plurality of magnetic particles may also have a resonance frequency at which the magnetic particles respond to an oscillating magnetic field by producing heat that heats solution 305 by induction. The resonance frequency of each magnetic particle may include a range of resonance frequencies. In some examples, the plurality of magnetic particles have separate and distinct resonance frequencies. In some examples, the plurality of magnetic particles may have overlapping resonance frequencies. For instance, magnetic particles of the first type 313 may have a separate and distinct resonance frequency, whereas magnetic particles of the second type 315 have a resonance frequency that at least partially overlaps with the magnetic particles of the third type 319, and/or magnetic particles of the fourth type 321 . In some examples, each of the plurality of polymeric particles includes a primer for the temperature-sensitive reaction conjugated to a surface of the polymeric particle, as discussed with regards to FIG. 4.

[0038] FIG. 4 illustrates an example composition 41 1 including a plurality of polymeric particles 417-1 , 417-2, 417-n (referred to collectively as “polymeric particles 417”) suspended in solution 405, each polymeric particle including a primer for a temperature-sensitive reaction, in accordance with the present disclosure. As described with regards to FIG. 3, magnetic particles of the first type (e.g., 413-1 , 413-2, and 413-n) may have a first Curie temperature, while magnetic particles of the second type (e.g., 415-1 , 415-2, and 415-n) may have a second Curie temperature, magnetic particles of the third type (e.g., 419-1 , 419-2, and 419-n) may have a third Curie temperature, and magnetic particles of the fourth type (e.g., 421 -1 , 421 -2, and 421 -n) may have a fourth Curie temperature.

[0039] As illustrated, polymeric particle 417-1 may include primer 423-1 , polymeric particle 417-2 may include primer 423-2, and polymeric particle 417-n may include primer 423-n. Although each polymeric particle 417 is illustrated with a single primer, examples are not so limited. For instance, each of the polymeric particles 417 may include a plurality of primers. In yet further examples, each of the plurality of polymeric particles 417 may include an enzyme for the temperature-sensitive reaction conjugated to a surface of the polymeric particle, as illustrated in FIG. 5.

[0040] FIG. 5 illustrates an example composition 51 1 including a plurality of polymeric particles 517-1 , 517-2, 517-n (referred to collectively as “polymeric particles 517”) suspended in solution 505, each including an enzyme for a temperature-sensitive reaction, in accordance with the present disclosure. As described with regards to FIG. 3, magnetic particles of the first type (e.g., 513-1 , 513-2, and 513-n) may have a first Curie temperature, while magnetic particles of the second type (e.g., 515-1 , 515-2, and 515-n) may have a second Curie temperature, magnetic particles of the third type (e.g., 519-1 , 519-2, and 519-n) may have a third Curie temperature, and magnetic particles of the fourth type (e.g., 521 -1 , 521 -2, and 521 -n) may have a fourth Curie temperature. In some examples, enzyme 523-1 may be conjugated to the surface of polymeric particle 517-1 , enzyme 523-2 may be conjugated to the surface of polymeric particle 517-2, and enzyme 523-n may be conjugated to the surface of polymeric particle 517-n.

[0041] 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. In some examples, each of the plurality of magnetic particles are coated in a silica layer. As discussed with regards to FIG. 1 , the magnetic particles may be disposed within a solution 505, as may be contained within a microreaction chamber of an apparatus (e.g., 103 illustrated in FIG. 1 ). [0042] FIG. 6 illustrates an apparatus for heating a solution for a temperaturesensitive reaction, in accordance with the present disclosure. FIG. 6 illustrates an example apparatus 625, comprising a microreaction chamber 603 extending a length 629 of the apparatus 625, and a solution 605 for a temperaturesensitive reaction enclosed within the microreaction chamber 603. In some examples, the solution 605 includes 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 the temperature-sensitive reaction, and a first resonance frequency at which the magnetic particles respond to an oscillating magnetic field. As illustrated in FIG. 6, the walls of the microreaction chamber 603 may be defined by chamber walls 627.

[0043] In some examples, the apparatus 625 includes a plurality of magnetic particles having particular Curie temperatures conducive for heating the solution 605 to a plurality of temperatures of the temperature-sensitive reaction. In such examples, the apparatus 625 may 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 temperaturesensitive reaction, and a second resonance frequency at which the magnetic particles respond to the oscillating magnetic field.

[0044] As discussed with regards to FIGs. 3, 4, and 5, the solution 605 may include a plurality of polymeric particles, wherein each of the polymeric particles includes a polymeric matrix, and a sub-part of the plurality of magnetic particles of the first type. For instance, the solution 605 may include a plurality of polymeric particles, wherein each of the polymeric particles includes a polymeric matrix and a sub-part of 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. Similarly, the solution 605 may include a plurality of polymeric particles, wherein each of the polymeric particles includes a polymeric matrix, a sub-part of the plurality of magnetic particles of the first type, and a sub-part of a plurality of magnetic particles of a second type wherein the second type of magnetic particles have the first Curie temperature, and a second resonance frequency at which the magnetic particles respond to the oscillating magnetic field.

[0045] FIG. 7 illustrates a block diagram of an example method 730 for heating a solution for a temperature-sensitive reaction, in accordance with the present disclosure. Particularly, the method 730 relates to a method of using the magnetic particles for heating a solution for PCR. The method 730 begins at 731 with mixing a sample with magnetic polymeric particles. Although the method 730 illustrates mixing a sample with magnetic polymeric particles, examples are not so limited. In some examples, the sample is mixed with magnetic particles that are not embedded in a polymeric matrix. At 733, the method 730 includes pumping the solution through a reaction chamber, such as chamber 603 illustrated in FIG. 6. Accordingly, the apparatus 625 may include resistors, such as thermal inkjet (TIJ) resistors and/or piezoelectric resistors to pump the solution through the chamber 603.

[0046] At 735, the method 730 includes turning a magnet on to capture polymeric particles onto a designated region. For instance, referring again to FIG. 6, the apparatus 625 may include a magnet disposed along the length 629 of the apparatus. The magnet may secure the magnetic particles in a particular place for the temperature-sensitive reaction.

[0047] At 737, the method 730 includes introducing a wash buffer into the chamber, and purging a sample carrier fluid. For instance, during polymerase chain reaction (PCR), a wash buffer may help wash away a carrier fluid that transported the sample to be amplified, while the magnet holds the nucleic acid sample in place.

[0048] At 739, the method 730 includes resuspending the polymeric particles by turning off the magnet and turning on a mixer. The mixer may dislodge samples from the polymeric particles, as may be coupled via promoters and/or enzymes. [0049] At 741 , the method 730 includes adding mastermix to the microreaction chamber, and replacing (e.g., adding back in) the wash buffer. As used herein, mastermix refers to a solution of reagents for PCR. While this example method pertains to amplification of nucleic acids by PCR, examples are not so limited, and the apparatus and methods described herein may equally apply to other temperature-sensitive reactions not including PCR.

[0050] At 743, the method 730 includes resuspending the polymeric particles again by turning off the magnet and turning on the mixer again. At 745, the method 730 includes initiating thermocycling on the polymeric particles. As discussed herein, thermocycling of the polymeric particles may be achieved by exposing the microreaction chamber to an oscillating magnetic field. A plurality of different temperatures may be achieved through changing the frequency of the oscillating magnetic field, thereby allowing the microreaction chamber to achieve a plurality of different temperatures without the use of an external heat source and/or temperature sensors within the microreaction chamber. At 747, the method 730 includes reading the result or results of the reaction, such as detecting whether a particular nucleic acid sequence has been amplified by the reaction.

[0051] FIG. 8 illustrates a block diagram of an example method 850 for heating a solution for a temperature-sensitive reaction, in accordance with the present disclosure. The method 850 begins at 851 with mixing a sample with magnetic polymeric particles. Although the method 850 illustrates mixing a sample with magnetic polymeric particles, examples are not so limited. In some examples, the sample is mixed with magnetic particles that are not embedded in a polymeric matrix. At 853, the method 850 includes pumping the solution through a reaction chamber, such as chamber 603 illustrated in FIG. 6. Accordingly, the apparatus 625 may include resistors, such as thermal inkjet (TIJ) resistors and/or piezoelectric resistors to pump the solution through the chamber 603. [0052] At 855, the method 850 includes turning a magnet on to capture polymeric particles onto a designated region. For instance, referring again to FIG. 6, the apparatus 625 may include a magnet disposed along the length 629 of the apparatus. The magnet may secure the magnetic particles in a particular place for the temperature-sensitive reaction.

[0053] At 857, the method 850 includes introducing a wash buffer into the chamber, and purging a sample carrier fluid. For instance, during polymerase chain reaction (PCR), a wash buffer may help wash away a carrier fluid that transported the sample to be amplified, while the magnet holds the nucleic acid sample in place.

[0054] At 859, the method 850 includes resuspending the polymeric particles by turning off the magnet and turning on a mixer. The mixer may dislodge samples from the polymeric particles, as may be coupled via promoters and/or enzymes. [0055] At 861 , the method 850 includes adding mastermix to the microreaction chamber, replacing the wash buffer, and eluting the nucleic acids (NAs) in the solution. At 863, the method 850 includes resuspending the polymeric particles by turning off the magnet, turning on the mixer, and promoting elution. At 865, the method 850 includes turning the magnet on, capturing polymeric particles onto a designated region in the microreaction chamber, and at 867, the method 850 includes moving the solution with nucleic acid to another microreactor. At 869, the method 850 includes initiating thermocycling directly on the polymeric particles, and at 871 , the method 850 includes reading the result(s) of the reaction.

[0056] 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 composition, comprising: a solution for a temperature-sensitive reaction; 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 the 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.

2. The composition of claim 1 , further including a plurality of polymeric particles, wherein each of the polymeric particles includes: a polymeric matrix; a sub-part of the plurality of magnetic particles of the first type; and a sub-part of the plurality of magnetic particles of the second type.

3. The composition of claim 2, wherein each of the plurality of polymeric particles includes a primer for the temperature-sensitive reaction conjugated to a surface of the polymeric particle.

4. The composition of claim 2, wherein each of the plurality of polymeric particles includes an enzyme for the temperature-sensitive reaction conjugated to a surface of the polymeric particle.

5. The composition of claim 1 , wherein the plurality of magnetic particles consist essentially of iron oxide, a soft ferrite, a ferromagnetic material, a ferrimagnetic material, or combinations thereof.

6. The composition of claim 1 , wherein each of the plurality of magnetic particles are coated in a silica layer.

7. A method comprising: placing a microreaction chamber into an oscillating magnetic field, wherein the microreaction chamber encloses a solution for a temperaturesensitive reaction, the solution 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 the 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.

8. The method of claim 7, wherein 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.

9. The method of claim 8, wherein 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.

10. The method of claim 8, 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.

11. An apparatus, comprising: a microreaction chamber extending a length of the apparatus; and a solution for a temperature-sensitive reaction enclosed within the microreaction chamber, the solution 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 the temperature-sensitive reaction, and a first resonance frequency at which the magnetic particles respond to an oscillating magnetic field.

12. The apparatus of claim 11 , further including 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 temperaturesensitive reaction, and a second resonance frequency at which the magnetic particles respond to the oscillating magnetic field.

13. The apparatus of claim 11 , further including a plurality of polymeric particles, wherein each of the polymeric particles includes: 22 a polymeric matrix; and a sub-part of the plurality of magnetic particles of the first type.

14. The apparatus of claim 11 , further including a plurality of polymeric particles, wherein each of the polymeric particles includes: a polymeric matrix; and a sub-part of 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.

15. The apparatus of claim 11 , further including a plurality of polymeric particles, wherein each of the polymeric particles includes: a polymeric matrix; a sub-part of the plurality of magnetic particles of the first type; and a sub-part of a plurality of magnetic particles of a second type wherein the second type of magnetic particles have the first Curie temperature, and a second resonance frequency at which the magnetic particles respond to the oscillating magnetic field.