TW201808426A - Self-drive microfluidic filtration device, microfluidic filtration device and microfluidic driver enabling screening of blood samples quickly and conveniently without cross-contamination of samples occurred during the separation and screening processes in prior arts - Google Patents

Abstract

The present invention discloses a self-drive microfluidic filtration device, a microfluidic filtration device and a microfluidic driver. One embodiment of the self-drive microfluidic filtration device includes a microfluidic filter part, a microfluidic driving part, and a connecting channel. One embodiment of the microfluidic filter part includes a first fluid receiving chamber, a porous filter unit and a second fluid receiving chamber, wherein the first fluid receiving chamber, the porous filter unit and the second fluid receiving chamber are disposed in sequence along a counter-gravity direction. One embodiment of the microfluidic driving part includes a first chamber and a liquid adsorption unit, wherein working fluid is accommodated in the first chamber. In this embodiment, after the liquid is filled into the first fluid receiving chamber, the liquid adsorption unit is used to absorb the working fluid in the first chamber, so that the first chamber generates a negative pressure for driving the liquid in the first fluid receiving chamber to flow toward the direction of the first chamber and pass through the porous filter unit.

Description

Self-driving type microfluidic filtering device, microfluidic filtering device and microfluidic driving device

The invention relates to a microfluidic filtering device and a microfluidic driving device; in particular, it relates to a self-driven microfluidic filtering device.

In response to the current medical needs for preventive medicine, early diagnosis and early treatment, the demand for automated test environments, Point of Care (POC) or Near Patient Testing and molecular diagnostics has increased.

According to statistics from the pharmaceutical market research agency Kalorama Information, the global market value of In Vitro Diagnostics (IVD) in 2011 was approximately US $ 50.9 billion, and the market value of cardiovascular biomarker laboratory immunoassay tests in 2011 was approximately US $ 1.3 billion. It is estimated to reach USD 1.45 billion in 2016, accounting for 10% of immunoassay tests. Cardiovascular specialist-based point-of-care testing (Professional POCT) has a market value of approximately $ 500 million in 2011 and an estimated $ 650 million in 2016. In total, the cardiovascular immune analysis in 2011 exceeded 1.8 billion U.S. dollars, and the growth rate of point-of-care testing (POCT) was higher than that of laboratory analysis.

At present, most blood samples are still separated in centrifuges, and the separated samples are taken out to the tester or quick-screen cassette for testing. Because this kind of disposal method requires separate separation devices and screening devices for testing , Can not make general users fast and convenient to use, the process may cause cross-contamination of the sample.

An embodiment of the present disclosure provides a self-driven microfluidic filtering device, which includes a microfluidic filtering portion, a microfluidic driving portion, and a connecting channel. The microfluidic filtering unit includes a first fluid containing cavity, a multi-porous filtering unit, and a second fluid containing cavity, and the first fluid containing cavity, the multi-porous filtering unit, and the second fluid containing cavity sequentially follow Disposition against the direction of gravity. In addition, the microfluidic driving part includes a first chamber and a liquid adsorption unit, wherein a working fluid is contained in the first chamber. The communication channel communicates with the second fluid receiving chamber of the microfluidic filtering section and the first chamber of the microfluidic driving section. The first fluid storage chamber includes an inlet. After the liquid is filled into the first fluid storage chamber from the inlet, the liquid adsorption unit is used to adsorb the working fluid in the first chamber to generate a negative pressure in the first chamber to drive the first chamber. The liquid in the fluid storage chamber flows in the direction of the first chamber and flows through the porous filter unit.

An embodiment of the present disclosure provides a microfluidic filtering device, which includes a first fluid containing cavity, a multi-porous filtering unit, and a second fluid containing cavity. The first fluid storage cavity, the porous filter unit, and the second fluid storage cavity are sequentially arranged along a direction of anti-gravity. The first fluid storage cavity includes an inlet, and the liquid can be filled into the first fluid storage cavity through the inlet and needs to flow through the multi-porous filter unit to the second fluid storage cavity in the direction of anti-gravity.

An embodiment of the disclosure provides a microfluidic driving device including a liquid containing chamber, a first chamber communicating with the liquid containing chamber, and a liquid adsorption unit. A working fluid is contained in the first chamber. The liquid adsorption unit is used to adsorb the working fluid in the first chamber, so that a negative pressure is generated in the first chamber, and the liquid in the liquid containing chamber is driven to flow in the direction of the first chamber.

In order to make the above features and advantages of the present invention more comprehensible, embodiments are hereinafter described in detail with reference to the accompanying drawings.

FIG. 1A is a schematic side sectional view of a microfluidic filtering device 100 according to an embodiment of the present invention. FIG. 1B is an enlarged schematic view of a partial area of the microfluidic filtering device 100 in the embodiment of FIG. 1A. Please refer to FIG. 1A first. The microfluidic filtering device 100 of this embodiment includes a structure body 100B. In this embodiment, the structural body 100B is, for example, a sheet-shaped body, but the present invention is not limited thereto. The structural body 100B of the microfluidic filtering device 100 can distinguish at least three structural configuration portions therein. The three structural configuration portions are a microfluidic filtering portion 110, a microfluidic driving portion 120, and a connecting channel 130, respectively.

In the embodiment of FIG. 1A, the microfluidic sample may be, for example, a blood sample 101, but the present invention is not limited thereto. After the blood sample 101 is input through the inlet 1101 of the microfluidic filter unit 110, the blood sample 101 is collected in the first fluid storage chamber 1102 in the microfluidic filter unit 110. The microfluidic filtering unit 110 further includes a multi-porous filtering unit 1103 and a second fluid storage cavity 1104. The first fluid storage cavity 1102 in at least a part of the region and the multi-porous filter portion 1103 and the second fluid storage cavity 1104 in at least a part of the region are sequentially arranged from the bottom to the top of the microfluidic filter 110, such as the first in the embodiment of FIG. The area A of the fluid storage cavity 1102, the porous filter portion 1103, and the area B of the second fluid storage cavity 1104 are sequentially arranged along the Z direction (that is, the direction of anti-gravity, for example) from bottom to top.

FIG. 1B is an enlarged schematic view of a partial area of the microfluidic filtering device 100 in the embodiment of FIG. 1A, especially the area A of the first fluid receiving cavity 1102, the multi-porous filtering portion 1103 and the second fluid receiving cavity 1104 in the microfluidic filtering portion 110. An enlarged view of a partial region of the region B. It can be known from the foregoing that the region A of the first fluid storage cavity 1102, the porous filter portion 1103, and the region B of the second fluid storage cavity 1104 in this embodiment are sequentially arranged from bottom to top along the direction of antigravity. Referring to the embodiment of FIG. 1B, due to the larger proportion of the blood cells 101a in the blood compared to the plasma, after a short period of standing time, the blood cells will first settle in the lower part of the first fluid storage cavity 1102, that is, in the blood. Most of the blood cells will be distributed in the area A of the first fluid containing cavity 1102 away from the area below the porous filter portion 1103.

Referring again to the embodiment of FIG. 1A, the microfluidic driving unit 120 stores a working fluid 1201 in a first chamber 1202 therein, and the first chamber 1202 communicates with the microfluidic filtering unit 110 through the communication channel 130. The microfluidic driving unit 120 further includes a partition unit 1203 and a liquid adsorption unit 1204. The partition unit 1203 partitions the working fluid 1201 from the liquid adsorption unit 1204.

FIG. 1C to FIG. 1D are operation schematic diagrams of the microfluidic filtering device in the embodiment of FIG. 1A. When the microfluidic filtering device 100 of the embodiment of FIG. 1A is used, after the blood sample 101 is statically placed in the first fluid storage chamber 1102, a force can be applied to the first chamber 1202, for example, the force F shown in FIG. 1C, The working fluid 1201 in the first chamber 1202 is driven to the liquid adsorption unit 1204.

Please refer to FIG. 1C to FIG. 1E again. When the working fluid 1201 in the first chamber 1202 is adsorbed by the liquid adsorption unit 1204, the first chamber 1202 will generate a negative pressure accordingly. Since the first chamber 1202 is in communication with the second fluid receiving chamber 1104 of the microfluidic filtering unit 110 through the communication channel 130, the negative pressure in the first chamber 1202 can further drive the first fluid receiving chamber 1102 of the microfluidic filtering unit 110. The blood sample 101 flows through the porous filter unit 1103 and flows to the second fluid storage cavity 1104.

It can be known from the foregoing FIG. 1B that, since the area A of the first fluid storage cavity 1102, the porous filter portion 1103, and the area B of the second fluid storage cavity 1104 in the microfluidic filter portion 110 of this embodiment are in the direction of antigravity. The distribution is sequentially arranged from the bottom to the top, so that most of the blood cells in the blood sample 101 settle to the lower part of the first fluid storage chamber 1102 due to the specific gravity relationship, so the negative pressure driving force through the rear microfluidic driving part 120 Most of the blood samples passing upward through the porous filter unit 1103 are plasma with a small specific gravity.

In this embodiment, the multi-porous filter unit 1103 is, for example, a filter membrane containing multiple pores, and the pore diameter of the pores is preferably less than or equal to 2 micrometers (mm). In one embodiment, the porous filter membrane may further have a hydrophilic asymmetric porous material, such as a plasma separation membrane (Plasma Separation Membrane), but the present invention is not limited thereto. In another embodiment, the pore diameter of the pores close to the first fluid storage cavity 1102 in the asymmetric multi-porous filter membrane is larger than the pore diameter of the pores close to the second fluid storage cavity 1104, which can be further filtered out. Plasma without or less blood cells. In this embodiment, the arrangement of the anti-gravity configuration structure in the microfluidic filtering unit 110 allows most of the blood cells in the blood sample to settle in the first fluid storage cavity 1102 instead of being accumulated in the pores of the multi-pore filtering unit 1103, which can reduce or avoid The hemolysis in the plasma passing through the porous filter unit 1103 is caused by the accumulation of blood cells in the pores and the force is broken. In another embodiment, the pore size configuration of the asymmetric multi-porous filter membrane can be further matched to achieve a buffer filtration method to increase the filtered plasma composition and reduce the hemolysis phenomenon.

In one embodiment, the liquid adsorption unit 1204 may be made of a porous water-absorbing fiber material, for example. According to Darcy's law and Stroke's law fluid mechanics model analysis, as shown in formula (1) and formula (2) below, the working fluid 1201 is subjected to the porous material of the liquid adsorption unit 1204 Porous flow is induced, which creates a negative pressure ( Pcapillary) further induces the pipe flow generated in the pipe. According to formula 2, the smaller the porosity of the porous water-absorbing material, the larger the flow will be. Therefore, by selecting the liquid adsorption unit 1204 as a micro-sized porous water-absorbing fiber material, a driving pressure of kilopascal (kPa) level can be generated, which is larger than the driving pressure of hundreds of Pascals which is based on the capillary force principle. . Formula (1) Formula (2)

Please refer to the embodiment of FIG. 1E. In some applications, at least a certain amount of plasma samples need to be separated for the reagent detection in the back end. The volumetric flow rate Qworking that meets the requirements can be designed according to the aforementioned formula (1), and according to Darcy's law and Young-Laplace pressure formula, as shown in formula (3) below, select The specifications of the liquid adsorption unit 1204 that meet the requirements, such as the shape and material, realize that it can continuously generate negative pressure to induce more pipeline flow and generate plasma that meets the design requirements. Formula (3)

FIG. 2A and FIG. 2B are a schematic plan view and an explosion view of a microfluidic filtering device 100 'according to an embodiment of the present invention, respectively. Please refer to FIG. 2A first. The microfluidic filtering part 110 'of this embodiment is distributed in the lower half of FIG. 2A, and includes a fluid inlet 1101', a first fluid receiving cavity 1102 ', a multi-porous filtering unit 1103', and a second fluid receiving Cavity 1104 '. In addition, the microfluid driving part 120 'is distributed in the upper half of Fig. 2A, and includes a working fluid 1201', a first chamber 1202 'in which the working fluid is placed, a partition unit 1203', and a liquid adsorption unit 1204 '. Wherein, the first chamber 1202 'in the upper half of the embodiment of FIG. 2A includes a continuous curved flow channel in which the working fluid 1201' is placed, but the present invention is not limited thereto, and one end of the first chamber 1202 'passes through the connecting channel 130 'Communicates with the second fluid receiving cavity 1104' in the lower half. In this embodiment, the second fluid storage chamber 1104 'may further be provided with a test paper, such as the dengue antigen test strip in FIG. 2A, but the present invention is not limited thereto. In this way, the needs of fast screening can be further met.

Referring to the embodiment of FIG. 2B, the partition unit 1203 'is disposed between the continuous curved flow path (the first chamber 1202') where the working fluid is placed and the liquid adsorption unit 1204 'and is used to separate the working fluid 1201' from the liquid adsorption unit. 1204 ', for example, the dotted area where the separation unit 1203' is located is shown in FIG. 2B. In one embodiment, the separation unit 1203 'is, for example, a bubble gap, and the bubble gap is located in the continuous curved flow channel (first chamber 1202') near the liquid adsorption unit 1204 'to separate the continuous curved flow channel 1202. 'With the liquid adsorption unit 1204', when using the microfluidic filtering device of this embodiment, the bubble gap is advanced to the liquid adsorption unit 1204 'by the aforementioned force F applied to the first chamber 1202', so that the first A chamber 1202 'is in communication with the liquid adsorption unit 1204'.

In another embodiment, the partition unit 1203 'in the embodiment of FIG. 2B may be a film that is susceptible to partial hole force and breaks holes, such as an aluminum foil film. In another embodiment, the partition unit 1203 'may be a wax plug. When the microfluidic filtering device of this embodiment is used, a heat treatment may be applied to the area of the partition unit 1203' to melt the wax plug.

Please refer to the embodiment of FIG. 2B again. The structure body 100B 'of the microfluidic filter device 100' can be composed of an upper plate 100U and a lower plate 100D sandwiching a substrate 100M, but the invention is not limited thereto. In this embodiment, the substrate 100M includes an injection hole 1202I. The aforementioned working fluid 1201 'can be injected into the continuous curved flow channel of the first chamber 1202' through the injection hole 1202I, but the present invention is not limited thereto. Wherein, the material of the upper plate 100U or the lower plate 100D may include polymethylmethacrylate (PMMA), polycarbonate (PC), pressure-sensitive adhesive, Cyclo olefin polymer (COP), or polybenzene High polymer plastic materials such as polystyrene (PS). The material of the substrate 100M may include polymethylmethacrylate (PMMA), polycarbonate (PC), pressure-sensitive adhesive, Cyclo olefin polymer (COP), or polystyrene (PS). ) And other polymer plastic materials. In an embodiment, the upper plate 100U corresponding to the injection hole 1202I of the substrate 100M may further include an opening corresponding to the injection hole 1202I, and the working fluid 1201 ′ may be combined in the upper plate 100U, the lower plate 100D, and the substrate 100M. It is then injected into the first chamber 1202 'from the aforementioned corresponding opening in the upper plate 100U.

FIG. 3 is a schematic top view of a microfluidic filtering device according to another embodiment of the present invention. The microfluidic filtering device of this embodiment is similar to the embodiment of FIG. 2A described above, and therefore is represented by the same or similar component symbols as those of FIG. 2A. Referring to the embodiment of FIG. 3, the second fluid storage cavity 1104 ′ in the microfluidic filtering unit 110 ′ may further include a magnetic droplet controlled flow channel, and the flow channel is used for containing a magnetic liquid droplet (not shown). The magnetic droplet includes, for example, magnetic beads and an object to be detected. In this embodiment, the flow channel includes a plurality of separated control spaces 1104a. In this embodiment, the user can control the movement of the object to be measured in different control spaces by manipulating the external magnetic field. The user can also accommodate different liquids in different control spaces 1104a according to his needs, thereby the user Operations such as pre-processing, detection, or post-processing can be performed in different control spaces 1104a.

Fig. 4A is a schematic top view of a microfluidic filtering device according to another embodiment of the present invention, and Fig. 4B is a schematic cross-sectional view taken along line A-A 'of Fig. 4A. The microfluidic filtering part of the microfluidic filtering device of this embodiment is similar to the embodiment of FIG. 2A described above, and therefore is represented by the same or similar component symbols as those of FIG. 2A. Please refer to FIG. 4B first. In this embodiment, the separation unit 1203 'can use the same plastic material as the aforementioned substrate 100M, so the separation unit 1203' can be, for example, a plastic sheet and integrally formed with the substrate 100M, that is, the separation unit 1203 'can be integrally formed with the structural body 100B. In this embodiment, the thickness of the plastic sheet integrally formed in the structural body 100B is, for example, not more than 0.2 millimeter (mm), but the present invention is not limited thereto.

Please refer to the embodiment of FIGS. 4A and 4B again. In this embodiment, the liquid adsorption unit 1204 'and the working fluid 1201' are respectively placed on the upper and lower sides of the partition unit 1203 ', and the structure body 100B adjacent to the liquid adsorption unit 1204' A micro-breathing hole 1204O is provided at the part. When the microfluidic filtering device of this embodiment is used, after the partition unit 1203 '(for example: a plastic sheet) is crushed by a force, the liquid adsorption unit 1204' will contact and adsorb the working fluid 1201 ', so that the first chamber 1202 'Negative pressure is generated to drive the first chamber 1202', and the specimen in the front-end communication liquid containing chamber (for example, the first fluid storage chamber or the second fluid storage chamber) flows in the direction of the first chamber 1202 '.

Although this proposal is disclosed above with the foregoing preferred embodiments, it is not intended to limit this proposal. Any person skilled in similar arts can make some changes and decorations without departing from the spirit and scope of this proposal. The scope of patent protection proposed shall be determined by the scope of patent application attached to this specification.

100, 100'‧‧‧ microfluidic filter device
100B, 100B'‧‧‧ structure body
100U‧‧‧on board
100D‧‧‧ Lower plate
100M‧‧‧ substrate
101‧‧‧ blood sample
101a‧‧‧ blood cells
110, 110'‧‧‧ microfluidic filtration department
1101, 1101'‧‧‧ entrance
1102, 1102'‧‧‧ first fluid storage cavity
1103, 1103'‧‧‧ multi-porous filter unit
1104, 1104'‧‧‧Second fluid storage cavity
1104a‧‧‧Control Space
120, 120'‧‧‧ microfluidic driver
1201, 1201'‧‧‧ Working fluid
1202, 1202'‧‧‧ First Chamber
1202I‧‧‧Working fluid injection hole
1203, 1203'‧‧‧ partition unit
1204, 1204'‧‧‧ liquid adsorption unit
1204O‧‧‧Micro vent
130, 130'‧‧‧ with access

FIG. 1A is a schematic side sectional view of a microfluidic filtering device according to an embodiment of the present invention. FIG. 1B is an enlarged schematic view of a partial area of the microfluidic filtering device in the embodiment of FIG. 1A. FIG. 1C to FIG. 1E are operation schematic diagrams of the microfluidic filtering device in the embodiment of FIG. 1A. FIG. 2A is a schematic top view of a microfluidic filtering device according to an embodiment of the present invention. FIG. 2B is an exploded view of the microfluidic filtering device in the embodiment of FIG. 2A. FIG. 3 is a schematic top view of a microfluidic filtering device according to an embodiment of the present invention. FIG. 4A is a schematic top view of a microfluidic filtering device according to another embodiment of the present invention. Fig. 4B is a schematic cross-sectional view taken along line A-A 'of Fig. 4A.

100‧‧‧ microfluidic filter device

100B‧‧‧ Structure Ontology

101‧‧‧ blood sample

110‧‧‧Microfluidic filtration department

1101‧‧‧ Entrance

1102‧‧‧First fluid storage cavity

1103‧‧‧Porous Filter Unit

1104‧‧‧Second fluid storage cavity

120‧‧‧Microfluidic drive unit

1201‧‧‧working fluid

1202‧‧‧First Chamber

1203‧‧‧ Divided Unit

1204‧‧‧Liquid adsorption unit

130‧‧‧ with access

Claims (15)

A self-driven microfluidic filtering device includes: a microfluidic filtering section including a first fluid storage cavity having an inlet for inputting and containing a liquid; a multi-porous filtering unit for filtering the liquid; and A second fluid containing cavity for containing the filtered liquid, wherein the first fluid containing cavity, the multi-porous filter unit and the second fluid containing cavity are sequentially arranged along an anti-gravity direction; a micro The fluid driving part includes a first chamber for containing a working fluid; and a liquid adsorption unit for adsorbing the working fluid; and a connecting channel for communicating the second fluid storage of the microfluidic filtering part. The cavity and the first cavity of the microfluidic driving part. The self-driven microfluidic filtering device according to item 1 of the scope of patent application, wherein the microfluidic filtering part, the microfluidic driving part, and the connecting channel are disposed on a structural body. The self-driven microfluidic filtering device according to item 2 of the patent application scope, wherein the structural body comprises a sheet-shaped body. The self-driving microfluidic filtering device according to item 1 of the patent application scope, wherein the porous filter unit includes a filter membrane, and the filter membrane has a plurality of pores. The self-propelled microfluidic filter device according to item 4 of the scope of patent application, wherein the pore has a pore diameter of less than or equal to 2 microns. The self-driving microfluidic filtering device according to item 4 of the scope of application for a patent, wherein the filtering membrane is made of hydrophilic asymmetric pore material. The self-propelled microfluidic filter device according to item 4 of the scope of patent application, wherein the pores of the plurality of pores disposed near the first fluid receiving cavity in the filter membrane are larger than the plurality of pores adjacent to the second fluid receiving cavity. Pore diameter. The self-driving microfluidic filter device according to item 3 of the scope of patent application, wherein the structure body is composed of an upper plate and a lower plate sandwiching a substrate. The self-driving microfluidic filtering device according to item 8 of the scope of patent application, wherein the material of the upper plate or the lower plate includes polymethylmethacrylate (PMMA), polycarbonate (PC), and pressure-sensitive adhesive Cyclo olefin polymer (COP) or polystyrene (PS). The self-driving microfluidic filter device according to item 8 of the scope of patent application, wherein the material of the substrate includes polymethylmethacrylate (PMMA), polycarbonate (PC), pressure-sensitive adhesive, and cycloolefin polymer (Cyclo olefin polymer, COP) or polystyrene (PS). The self-driving microfluidic filtering device according to item 1 of the scope of patent application, wherein the microfluidic driving unit further includes a partition unit for separating the working fluid from the liquid adsorption unit, wherein the partition unit includes Air gap, aluminum foil film, wax plug or plastic sheet. The self-driving microfluidic filtering device according to item 8 of the scope of patent application, wherein the microfluidic driving unit further includes a partition unit for partitioning the working fluid from the liquid adsorption unit. According to the self-propelled microfluidic filtering device according to item 12 of the scope of the patent application, wherein the partition unit is a sheet of the same material as the substrate, and the sheet is integrally formed with the substrate. A microfluidic filtering device includes: a first fluid containing cavity having an inlet for inputting and containing a liquid; a multi-porous filtering unit for filtering the liquid; and a second fluid containing cavity for The liquid filtered by the porous filter unit is contained, wherein the first fluid storage chamber, the porous filter unit, and the second fluid storage chamber are sequentially arranged along an anti-gravity direction. A microfluidic driving device includes: a liquid containing chamber for containing a liquid; a first chamber for containing a working fluid, wherein the first chamber communicates with the liquid containing chamber And a liquid adsorption unit for adsorbing the working fluid in the first chamber so that a negative pressure is generated in the first chamber, driving the liquid in the liquid containing chamber to the first chamber The direction of the chamber flows.