RU207370U1 - A device with a microchannel structure made in volume - Google Patents

Abstract

The utility model relates to the fields of microfluidic technology and microreactor flow-through chemical synthesis, namely, to a flow-through microreactor of mixing, which is an integral object, in the volume of which small-diameter channels are made, located in three dimensions, having two or more injection points on their trajectory, additional channels heating the components and preparing for mixing the streams after entering the microreactor, the intersection of the mixing of streams with the place of mixing, the reaction channel made in the form of a cylindrical spiral and one or more points of product withdrawal. The utility model provides efficient mixing of liquids in the mixing zone and uniform heat transfer from the thermostating system to the flow of matter in the channels in the reaction zone. For better heat transfer, a hole can be made in the center of the reactor for installing a thermostatting unit. A utility model is produced by three-dimensional printing or another similar method, which consists in layer-by-layer reconstruction from a material, which makes it possible to adjust individual elements of the utility model to optimize for solving specific problems.

Description

This useful model relates to the field of microreactor flow synthesis and microfluidic technology, namely, to a flow-through microreactor of mixing.

The use of microreactor flow synthesis over capacitance synthesis offers advantages such as better mixing, more efficient heat transfer and easier scaling [Plutschack, MB, Pieber, B., Gilmore, K., Seeberger, PH The Hitchhiker's Guide to Flow Chemistry //, Chem. Rev. 2017, 117, 11796-11893.]. Another advantage of flow synthesis is the ability to carry out multistage reactions with multiple reactors in one system [Britton, J., Raston, C. L., Multi-step continuous-flow synthesis, Chemical Society Reviews 2017, 46, 1250-1271.]. One application for such multistage reactions is, for example, the production of pharmaceuticals on demand using compact modular continuous systems [Adamo, A., Beingessner, RL, Behnam, M., Chen, J., Jamison, TF, Jensen, KF, Monbaliu, J.-C. M., Myerson, AS, Revalor, EM, Snead, DR, Stelzer, T., Weeranoppanant, N., Wong, SY, Zhang, On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system, Science 2016, 352, 61-67.].

The utility model was developed to solve a number of problems associated with the use of three-dimensional printing from polymeric materials to obtain microreactors for flow-through synthesis. At the moment, the literature does not know the use of a design in which the reaction channel is executed in the volume of the entire body of an object in three dimensions in the form of a spiral.

The combination of flow-through synthesis with reactors obtained by the method of three-dimensional printing from polymeric materials is cost-effective due to the rather rapid development, rapid production of new samples, and the low cost of microreactors. 3D printing, also known as additive manufacturing, is a process in which an object is created layer by layer directly from a 3D model obtained in a computer-aided design program. There are many technologies that can allow printing microreactors for continuous flow, for example: fused deposition technology (FDM, FFF) [Neumaier JM, Madani A., Klein T., Ziegler T., Low-budget 3D-printed equipment for continuous flow reactions, Beilstein J. Org. Chem. 2019, 15, 558-566.], Selective laser sintering (SLS) [Elias, Y., Rudolf von Rohr, P., Bonrath, W., Medlock, J., Buss, A., A porous structured reactor for hydrogenation reactions, Chemical Engineering and Processing: Process Intensification, 2015, 95, 175-185], stereolithography (SLA) [Comina, G., Suska, A., Filippini, D., Low cost lab-on-a-chip prototyping with a consumer grade 3D printer, Lab on a Chip, 2014, 14, 2978-2982], inkjet 3D printing (3DP). However, each method has its own advantages and disadvantages. Printing using SLA, SLS, 3DP technologies allows you to get objects with high resolution, but the materials used in SLA and 3DP technologies have low chemical resistance and are suitable only for a small number of media and reactions. In the case of SLA technology, the object is obtained by sintering the raw material powder, which remains in the channels of the printed device, after which a number of problems arise with the removal of green powder from the channels. On the other hand, fused deposition technology is the most inexpensive of all, allows you to work with a variety of materials, but has the lowest print resolution. Layer-by-layer fusion technology allows working with polyethylene, polypropylene, thermoplastic polyurethane, polyetheretherketone and cycloolefins, all these materials can be used in the manufacture of microreactors according to the utility model.

A microreactor (microfluidic chip) is a device that is a single complex system of various sizes (usually from 1 mm to 10 cm) and allows conversion of reagent (s) to product or sample for analysis. [Demello A.J. Control and detection of chemical reactions in microfluidic systems // Nature. 2006. Vol.442. No. 7101. P. 394-402.]. The microreactor is made in the form of a compact device, in the channels of which at one time there is a small amount of liquid or gas at normal or elevated pressures; channels with a diameter from 1 to 1000 micrometers are used to transform substances. The topology and design of a particular microreactor is determined by the operations for which it is planned to use it.

In the case of polymer microreactors, they represent an object of arbitrary shape, as a rule, close to a rectangular parallel to the pipid, in which a system of channels, reaction zones, mixing zones, auxiliary elements is formed during the printing process in a single production cycle, electrodes, sensors or other constructions that will be needed to complete the tasks.

The microreactor described in the invention was obtained by the technology of three-dimensional printing by layer-by-layer fusion from three chemically resistant materials polypropylene, thermoplastic polyurethane (TPU) and a cycloolifin copolymer (cycloolefin).

Each of the polymeric materials used to prepare the microreactor has its own advantages and disadvantages, both for the printing process and in the field of chemical resistance.

Microreactors made of polypropylene are completely opaque and allow working in environments of organic solvents, concentrated acids and alkalis, but it is impossible to create channels with less than 0.5 mm due to the peculiarities of the printing technology with this material. The operating temperature range is from -50 ° C to + 100 ° C, for some environments the temperature range may be narrowed.

Microreactors made of TPU are transparent and allow working in environments of aliphatic organic solvents, aqueous solutions of weak acids or alkalis. The operating temperature range is -50 ° C to + 100 ° C, for some environments there may be exceptions.

Microreactors made of cycloolefins, depending on the specific grade of material, can be either optically transparent or opaque, you can get different resistance to high or low temperatures in the range from -50 ° C to 200 ° C. They have high chemical resistance to all common reagents, except for halogenated hydrocarbons.

Microreactors produced by 3D printing have a significantly lower cost compared to glass or metal chips. The prime cost of polymer microreactors with the same parameters as glass ones is 10-20 times less due to the smaller number of operations that must be performed during the manufacturing process. At the same time, for polymer microreactors, there is no need to cover channels with additional compounds or their other modification due to low hydraulic resistance.

As a result, the cost of printed microreactors turns out to be less than that of analogs made of glass or metal, which makes it possible to make polymer microreactors disposable and get rid of problems with their cleaning, which is quite important in the case of work in the field of biotechnological production.

Description of patent search

A group of inventions is known from the prior art, including a tooling for obtaining a microfluidic chip blank, a method for producing a microfluidic chip blank, a microfluidic chip blank, a method for producing a microfluidic chip and a microfluidic chip [patent RU 2658495C1, 08.16.2018]. Installation for the formation of a microfluidic chip consists of two parts, one of which has a hole for pouring the molding material. In this case, the formation of channels occurs due to the relief contained on the inner surface of the tooling, which advises the topology of the manufactured microfluidic device.

From the prior art, a microfluidic mixing chip is known [RU 2724254 C1, 07.10.2019], which is made of glass or metal, is a plate on which the topology of a microfluidic device is made in one plane in one way or another in the form of channels of a certain shape and section and for the formation of a closed system is covered with a second plate of the same material, the sealing between the plates occurs, either due to the quality of the surfaces, or due to the adhesive base.

A blank of a microfluidic chip and a microfluidic chip for cultivation and / or research of cells is known from the prior art [RU 2675998C1, 02.02.2018]. The workpiece includes a plate with holes and a base. On one side of the base there is a layer of molding material with a microfluidic system of a given topology, and on the opposite side of the base there is a sealing layer in the form of a single elastic part made of molding material. In this case, the sealing layer is placed on the surface of the base and on the inner surface of the holes in the base. The microfluidic chip includes the aforementioned preform and a plate made of optically transparent material, fixed on the preform from the side of the microfluidic system, ensuring its sealing.

A method for producing pharmaceutical compositions based on polymer nanoparticles by the method of microfluidic technology is known from the prior art [RU 2637653C1, 08/10/2016]. The method consists in passing through a flow-through microreactor made of borosilicate glass an aqueous solution containing polyvinyl alcohol and a solution in acetone or acetonitrile of etoposide or niclosamide and a biodegradable polymer in the form of a copolymer of lactic and glycolic acids or its mixture with polymethyl methacrylate for medical use an aqueous solution of polyvinyl alcohol is preliminarily passed through a flow-through microreactor made of borosilicate glass.

A microfluidic chip for producing particles for drug delivery to a subject is known from the prior art [WO 2007150030 A2, 27.12.2007]. Microfluidic system for the production of organic particles, containing at least two channels that converge into a mixing device, in which the width or height of each channel is from 1 μm to 1000 μm, whereby fluid flow is able to flow through each channel and mixing device , and the streams from the at least two channels are connected and enter the mixing device, whereby the mixing device allows the production of organic particles.

A micromixer device (micro-mixer) is known from the prior art, comprising at least one liquid inlet and at least one liquid outlet; and a plurality of paths between one liquid inlet and one liquid outlet, the width of some of the plurality of paths being substantially parabolic along at least one micromixer size [US 8414182 B2, 09.04. 2013].

The utility model is a microreactor design designed for three-dimensional printing, which provides effective mixing of small volumes of liquids, reducing the consumption of reagents in chemical, biological synthesis or when used in analytical procedures.

The useful model is characterized by the fact that the microreactor is a solid object, performed in a single production cycle with a channel made in it, having two entry points on its trajectory [4], a potential channel for stabilization of the supplied flows, a mixing intersection of channels with a mixing point [2], the mixing channel [6], the reaction channel in the form of a spiral [3], the outlet point of the product [1] obtained as a result of mixing and reaction between the starting reagents and, optionally, holes for fastening in the cradle (Fig. 1).

A utility model at this stage in the development of technology cannot be made of glass or metal, or the manufacture of such an object will be economically inexpedient. In this case, an economically profitable printing of such a model from polymer materials is possible. In addition, the objects obtained as a result of printing do not require additional processing and can be used immediately after printing.

The described utility model can be obtained by layer-by-layer deposition using FFF (fused filament fabrication) or FDM (fused deposition modeling) technologies. As starting materials, special filaments are used, which are long threads, consisting, as a rule, of a polymer material having the composition necessary for the task.

The technical result of the claimed utility model is to expand the arsenal of microreactor devices and methods for their manufacture, in particular, mixing microreactors that provide effective mixing of liquids, without additional equipment, to intensify chemical flow synthesis, reduce the consumption of reagents, and reduce the hazard of chemical and biological industries due to minimization of the working volume. a reactor in which the reagents are mixed. The design of the microreactor according to this useful model provides an intensification of the mixing process of solutions with a short diffusion path and in due to the creation of special designs in the mixing channel.

The claimed microreactor is a closed sealed system of channels for mixing and movement of the reaction mass, with two inlets and, as a rule, one outlet of the reaction products. In this case, it is possible to manufacture a microreactor with additional points of entry, or to select a substance at any point in the reaction channel.

The technical result is achieved in that the microreactor according to the present invention can be made of thermoplastic polymeric materials or metals by three-dimensional printing or another similar method. A preferred embodiment of the present invention is a microreactor made of polypropylene or various grades of cycloolefins. The volume of the microreactor according to the present invention can be from 200 to 5000 µl, while the size of the microreactor can be: length, mm: from 20 to 100; width, mm: from 20 to 100; height, mm: from 28 to 250.

The described microreactor may contain channels for stabilizing the feed streams. Stabilization channels can have different channel geometries, different number of bends and different lengths. These channels are added to the topology of the microreactor in cases where it is necessary to additionally stabilize the state of the flows, their temperature, and also smooth out the unevenness of the flow before mixing the reactants. Channel parameters are selected empirically, depending on the tasks assigned to the microreactor. This improves the mixing efficiency of the two feed streams in the mixing channel.

The key areas of the utility model design, which ensure that the microreactor performs its functions, are the mixing point and channel and the reaction channel. The mixing point is the zone of the microreactor where two or more channels are connected (into which streams of mixed liquids or gases are fed). The channel in which special structures are made that intensify the mixing of the components is called the mixing channel (Fig. 1, number 6). The channel following the mixing channel is conventionally called the reaction channel (Fig. 1, number 3), since the necessary transformation of the initial components passes and ends in this zone of the microreactor.

The intersection of mixing channels in a microreactor is the place where two or more channels of the device meet and turn into one, according to the present invention, it can be made in the form of T-shaped, U-shaped or arrow-shaped intersections. The preferred embodiment, according to the present invention, is a mixing intersection made in a U-shaped or arrow-shaped form (Fig. 3, number 2).

The mixing channel of the present invention may be in the form of a serpentine channel, a straight flat channel with a modified surface, a zigzag channel, or a channel containing structures that induce flow eddies. The preferred embodiment according to the present invention is a mixing channel made in the form of a forward channel (Fig. 3, number 6).

The reaction channel according to the present invention is made in the form of a cylindrical spiral, while additional points of input or output of components can be removed from it.

The cross section of the channel in the microreactor according to the present invention can be made in the form of a square section, an oval section, a circular section, a semicircular section, or another shape. The preferred embodiment of the present invention is a circular cross-section. The diameter of the circular section of the duct can be in the range from 0.2 mm to 2 mm. In this case, the channel has a cross-sectional area from 0.13 mm ² to 3.2 mm ² , and its length can be from 100 to 1100 mm. In this case, the cross-sectional area of the channel along the entire length of the microreactor is the same.

When manufacturing the described utility model from polymeric materials, additional coating of the channel with a hydrophobic or other coating is not required to reduce the hydraulic resistance, since the starting materials provide these properties. In addition, as a result of printing, the surface of the microreactor channel is not absolutely smooth, but has a characteristic structure, which additionally affects the liquid flows inside the microreactor.

In the manufacture of the described utility model from polymeric materials, the reaction channel can be coated with an additional layer of materials necessary for being in the reaction mass in a solid aggregate state, for example, such a material can be a solid substance with the properties of a catalyst.

When manufacturing the described utility model, electrodes, ultrasonic and other emitters and other auxiliary elements can be installed in the reaction channel or next to it, depending on the tasks presented to the microreactor.

The flow rate of liquids into the claimed microreactor is selected empirically and depends on parameters such as the density of the liquids, the volume of the syringe pump and the nature of the components to be mixed. In doing so, the maximum operating values of the installation must be taken into account. The maximum operating value for the obtained microreactors according to the utility model ranges from 20 bar to 50 bar, depending on the specific design.

The declared microreactor can be installed in a special mount, which will provide the supply of substances into it and the output of the reaction products. The mount for the microreactor can be made of various materials, it is important that it provides a hermetic connection of capillaries (outer diameter - 1.6 mm, inner diameter - 0.5 mm) with the points of input and output of components from the microreactor. The connection of the micro-tractor with the capillaries is necessary for the introduction of the reaction media into the micro-reactor using pumps in a certain, precise ratio.

The applicant draws attention to the fact that the terms "microfluidic chip", "microreactor", "micromixer", "micromixer" in the present application are used interchangeably.

The present invention is illustrated by the accompanying images:

Brief description of the image:

1 - Product withdrawal point;

2 - Place of mixing of streams;

3 - Reaction spiral channel located in the volume of the reactor;

4 - Reagent injection points;

5 - the body of the microreactor;

6 - Zone of mixing flows, which can be modified for specific tasks.

Claims (13)

1. Microreactor of mixing, which is an integral object, performed in a single production cycle with a channel made in its volume, having two entry points on its trajectory, a potential channel for stabilization of feed streams, an intersection of mixing channels with a mixing point, a mixing channel, a reaction channel in the form spirals, the point of withdrawal of the product obtained as a result of mixing and the reaction between the initial reagents, where the volume of the microreactor is from 200 to 5000 μl. 2. A microreactor according to claim 1, manufactured using three-dimensional printing technology or similar to it. 3. The microreactor according to claim 1, wherein the microreactor is made of metals and their alloys. 4. The microreactor according to claim 1, where the microreactor is made of thermoplastic polymeric materials by layer-by-layer fusion technology. 5. The microreactor according to claim 1, wherein the channels have a square, oval, round or semicircular cross-sectional shape. 6. The microreactor of claim 5, wherein the channel has a circular cross-section. 7. The microreactor of claim 1, wherein the channel has a cross-sectional area of 0.13 mm ² to 3.2 mm ² . 8. The microreactor according to claim 1, where the mixing intersection is made in the form of a T-shaped, U-shaped or arrow-shaped intersection. 9. The microreactor according to claim 1, which has fasteners for hermetic connection of the capillary channels to the inlet and outlet openings. 10. The microreactor of claim 1, further having holes for mounting into the mount. 11. The microreactor according to claim 1, where the microreactor is fixed in the structure for hermetic connection of the capillary channels to the inlet and outlet openings. 12. The microreactor of claim 1, wherein the reaction channel is coated with a catalytic material. 13. Microreactor according to claim 1, in or near the reaction channel of which sensors, electrodes, emitters are installed.

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