JP2002371954A - Fluid transferring method, and fluid transferring device for micro fluid element - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method of simply transferring a fluid in a capillary by non-contacting, without requiring connection of piping or wiring, and a fluid transferring device for a micro fluid element using the transferring method. SOLUTION: In this fluid transferring method, magnetic fluid is introduced in a capillary flow passage, and a part where the magnetic fluid occupies the whole cross section of the flow passage is made to exist. Magnetism is added from the outside of the flow passage to move the magnetic fluid in a flow passage direction, and by using that as driving force, object fluid to be transferred is moved in the capillary flow passage. The fluid transferring device for a micro fluid element comprises a magnet (a mechanism moving the magnet or a magnetic line of force in the flow passage direction of the capillary, and/or a mechanism changing the strength of the magnetic line of force), and a mechanism holding the micro fluid element.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for transferring a fluid through a capillary channel formed in a microfluidic device. (Hereafter referred to as transfer target fluid)
And a method for transferring the same. The present invention also relates to a fluid transfer device for a microfluidic device capable of transferring a fluid in a microfluidic device by the fluid transfer method of the present invention.

The present invention relates to, for example, microchemical devices,
That is, micro devices for chemical and biochemical reactions (micro-reactors) in which structures such as micro channels and reaction vessels are formed; chemical devices such as membrane filtration devices, dialysis devices, degassing / aspiration devices, and extraction devices・ Physicochemical processing device; DNA analysis device, immunoanalysis device, electrophoresis device, chromatography, gas analysis device,
It can be used for microanalysis devices such as water quality analysis devices. The present invention can also be applied to a nozzle for manufacturing a microarray such as a DNA chip and an apparatus incorporating the nozzle.

[0003]

2. Description of the Related Art As a method of flowing a fluid through a capillary channel formed in a microfluidic device, a method using a pressure difference and a method using an electroosmotic flow when the fluid is an aqueous liquid are known. However, in the pressure difference method, it is necessary to connect a pipe for increasing or decreasing the pressure, and in the electroosmotic flow method, it is necessary to connect a wiring for driving voltage.

[0004] Therefore, when the microfluidic device in which the capillary is formed is a minute device, it is difficult to form a structure for connecting pipes and wiring, or the device needs to have strength for connection. And it is difficult to reduce the size of the device. In addition, there is an inconvenience that a very large number of parallel processes are difficult.

[0005]

An object of the present invention is to provide a method for easily transferring a fluid in a capillary without contacting pipes and wirings, and using the transfer method. An object of the present invention is to provide a fluid transfer device for a microfluidic device.

[0006]

Means for Solving the Problems As a result of intensive studies to solve the above-mentioned problems, the present inventor has filled a capillary channel with a magnetic fluid and moved it by magnetism. The inventors have found that it is possible to move the fluid to be transferred in the capillary channel using the movement of the magnetic fluid as a driving force, and have completed the present invention.

That is, according to the present invention, a magnetic fluid is introduced into a capillary channel so that the magnetic fluid has a portion occupying the entire cross-section of the channel, and magnetism is applied from outside the channel to provide a magnetic fluid. A fluid to be transferred, which is moved in the capillary channel by using this as a driving force.

[0008] The present invention also provides a method using the fluid transfer method,
Microfluidic device fluid transfer device, more specifically
(1) a magnet, (2) {a mechanism capable of moving a magnet or a line of magnetic force along the flow path of a capillary, and / or a mechanism capable of changing the intensity of a line of magnetic force}, and (3) holding a microfluidic device A fluid transfer device for a microfluidic device having a mechanism.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION A microfluidic device referred to in the present invention has a capillary channel inside (hereinafter referred to as a "capillary channel").
May be simply referred to as a “flow path”). The flow path referred to in the present invention refers to a cavity for moving a fluid in or through the flow path.In addition to a simple transfer flow path, a reaction flow path, a detection flow path, an extraction or other processing flow path, a valve, It may be a cavity of a pump section or the like. The transfer target fluid to be transferred in the flow path is arbitrary, and may be a liquid, a gas, or a supercritical fluid. Of course, the fluid can be a solution or a dispersion fluid.

[0010] The shape of the flow path is arbitrary. The shape in the length direction of the flow path is, for example, a straight line, a curve, a spiral, a zigzag, or another linear shape; a branch shape such as a dendritic shape, a comb shape, a radial shape, a mesh shape; a planar shape such as a circular or rectangular shape; Structures that become part of mechanisms such as membrane separation mechanisms, their connected shapes,
And so on. The channel may be open to the outside of the microfluidic device, may be connected to a pipe or another device, without opening to the outside, a mechanism provided in the microfluidic device, for example, a liquid storage tank Or to a waste liquid reservoir or the like.

The cross-sectional shape of the channel is arbitrary, and may be rectangular (including a rounded rectangle), trapezoidal, circular, semi-circular, slit-like, or any other complicated shape. As for the cross-sectional dimension of the flow channel, the width and the height are each preferably 3 μm to 3 mm, more preferably 10 μm to 1 mm. Also, the cross-sectional area is preferably 5 × 10 ⁻¹¹ m ^{2 to} 5 × 10
⁻⁶ m ² , more preferably 1 × 10 ⁻¹⁰ m ² to 1 × 1
0 ⁻⁶ m ² , most preferably 1 × 10 ⁻¹⁰ m ²
１1 × 10 ⁻⁷ m ² .

[0012] If the size is smaller than these dimensions, the transfer of the fluid becomes difficult. In addition, when these dimensions are exceeded, the driving force is reduced or the transfer becomes impossible. The above cross-sectional shape and cross-sectional dimensions are the shape and dimensions of the portion to be filled with the magnetic fluid, and other portions, for example, the portion through which the fluid to be phase-shifted passes are arbitrary, but are the same as above. Preferably, it is a dimension.

The magnetic fluid used in the present invention is a liquid material exhibiting ferromagnetism, specifically, a liquid material in which powder of a ferromagnetic solid such as iron oxide is stably dispersed in the liquid. In this case, the ferromagnetic solid and the dispersion medium are arbitrary, and can be selected according to the material of the microfluidic device in which the flow path is formed. For example, a ferromagnetic solid having a particle size that does not block the flow path can be selected and used, and a dispersion medium having a particle size that does not violate the microfluidic device can be selected and used.

The suitable viscosity of the magnetic fluid can be selected according to the cross-sectional area of the flow path and the transfer speed. For example, 100-1
0000 mPa / s can be preferably used. When the flow path cross-sectional area is small, a low viscosity one is preferable, and when the flow path cross-sectional area is large, a high viscosity one is preferable.

In the method of the present invention, a magnetic fluid is filled in a flow channel. At this time, it is necessary to fill the magnetic fluid so as to completely block the cross section of the flow channel in at least a part of the flow channel, but this state is usually realized without special work. The magnetic fluid fills a part of the flow path in the length direction of the flow path, and fills the remaining part of the flow path with the fluid to be transferred.

At this time, the whole amount of the magnetic fluid to be used may be filled in the channel, or a part of the magnetic fluid may be filled in the channel. In the latter case, the remaining amount may exist outside the microfluidic device and may be sequentially introduced into the flow path of the microfluidic device with the movement of the magnetic fluid, or may be sequentially introduced with the movement of the magnetic fluid. May flow out.
Needless to say, the magnetic fluid may not be present in the flow path at the beginning, end, or another time of the fluid transfer.

The flow path is also filled with a fluid to be transferred. At this time, the entire amount of the fluid to be transferred may be filled in the flow channel, or a part thereof may be filled in the flow channel, and the remaining amount may be outside the microfluidic device provided with the flow channel. . Of course, at the beginning of the fluid transfer, at the end, at other times,
The transfer target fluid may not be in the flow path.

The positional relationship between the fluid to be transferred and the magnetic fluid is arbitrary as long as the fluid to be phased is phased by the movement of the magnetic fluid as the driving force, and the fluid to be transferred is pushed by the magnetic fluid. It may be a position where it moves, a position where it is pulled and moved, or may be sandwiched between magnetic fluids, or may be sandwiched between magnetic fluids. Needless to say, the microfluidic device may have a plurality of portions filled with the fluid to be transferred, or a plurality of magnetic fluid filled portions.

When it is necessary to avoid contact with the magnetic fluid, such as when the fluid to be transferred is a fluid compatible with the magnetic fluid, or when it is necessary to separate the filling position of the fluid to be transferred from the magnetic fluid filling position. In some cases, for example, a third fluid (hereinafter, this fluid is referred to as “separation fluid”) may be placed between the fluid to be transferred and the magnetic fluid. The sequestering fluid is optional, and varies depending on the type of the fluid to be transferred. For example, a gas such as air, nitrogen, or argon; water or an aqueous solution; mineral oil; silicone oil;

The magnetic fluid filled in the flow path moves in the flow path by applying magnetism from outside the flow path, and accordingly, the fluid to be transferred also moves. The method of applying magnetism from outside the flow path is arbitrary, and may be, for example, magnetism generated by electric current (that is, magnetism by an electromagnet) or magnetism by a permanent magnet.

As a method for controlling the movement of the magnetic fluid, a method of changing the distance between the electromagnet or the permanent magnet and the magnetic fluid in the flow path; the distance between the electromagnet or the permanent magnet and the magnetic fluid is kept almost constant. A method of moving along a flow path as it is (including a method of moving a flow path or a microfluidic device);
A method of moving the magnetic field lines, such as a method of moving the magnetic field line shielding structure or the short path structure of the magnetic field lines, and a method of changing the current of the electromagnet; May be.

Among them, a method of generating magnetism by an electric current is preferred because it is easy to control, and a method that does not require changing the relative position between the microfluidic device and the magnetic generator, for example, changing the current of the electromagnet A method of moving magnetic field lines continuously or discretely by, for example, passing a current through wires at different positions sequentially. If the microfluidic device is a nozzle, the fluid to be transferred can be pulsed by moving the fluid to be transferred in a pulsed manner with a pulsed current.

The transfer of the fluid to be transferred is usually batchwise, and one transfer ends when the magnetic fluid reaches a position with the lowest potential, such as the outlet of the flow path. By a method of successively introducing into the flow path, or a method of returning the magnetic fluid to the original position using, for example, a valve or a valve,
The fluid can be transferred continuously.

Also, a trap is provided to prevent the magnetic fluid from flowing out of the outlet of the flow path, a separating mechanism of the magnetic fluid and the fluid to be transferred is used, and the magnetic fluid is reciprocated in the microfluidic element and used repeatedly. It is also possible to provide a mechanism such as the installation of a feedback circuit and a valve. Although it is possible to install the electromagnet in the microfluidic device, it is necessary to connect an electric wire to the microfluidic device.

The shape of the microfluidic device is arbitrary, and can be formed according to the application and purpose. For example, it may be in the form of a lump, a plate, a sheet (including a film, a ribbon, and a belt), a fiber (a hollow fiber), or the like. And the magnetic fluid filling portion may be a hollow fiber. When the microfluidic device is a microchemical device, it is preferably plate-shaped or sheet-shaped.

The flow path is formed by a member having a concave portion and a cover adhered to the surface thereof, or is formed by a defective portion of a layer sandwiched between at least two members. Is preferred.

A fluid transfer device for a microfluidic device according to the present invention is a device for transferring a fluid to a flow path in a microfluidic device using the liquid transfer method according to the present invention. More specifically, (1) a magnet (2) {a mechanism capable of moving a magnet or a magnetic line of force along the flow path of the capillary tube and / or a mechanism capable of changing the intensity of the magnetic line of force}, and (3) a magnetic line of force generated by the magnet of (1). And a mechanism for holding the microfluidic element at a position where the magnetic fluid can be moved.

Therefore, even if it has a magnet or a line of magnetic force, it is possible to move the magnetic fluid filled in the flow path of the microfluidic device by the line of magnetic force, such as a permanent magnet or an electromagnet for a motor. Those which cannot be performed are not included in the apparatus of the present invention. The type, shape, size, position, etc. of the magnet are not limited as long as they can drive the magnetic fluid filled in the flow path of the microfluidic device by the generated magnetism, but may be an electromagnet. preferable.

The magnet of this apparatus may be singular or plural. When there are a plurality of magnets, a plurality of electromagnets may each drive a group of different electromagnetic fluids, or a group of one electromagnetic fluid may be driven by a plurality of magnets.

The mechanism for spatially moving the magnetic field lines and / or the mechanism for changing the intensity of the magnetic field lines temporally include, for example,
It may be a magnet moving mechanism, a magnetic field line shielding mechanism driving mechanism, a magnetic field line short path mechanism driving mechanism, or when the magnet is an electromagnet, a current switch, a semiconductor switch, a transformer, a semiconductor current control circuit, a plurality of It may be a mechanism for sequentially supplying current to the electromagnet.

The change in the intensity of the magnetic field lines referred to here includes a change in the presence or absence of the magnetic field lines. An electric circuit that moves magnetic lines of force by sequentially passing a current through a plurality of arranged electromagnets may be used. These mechanisms may be sequence-controlled or feedback-controlled by computer control or the like. Further, the control mechanism for the magnetic field lines may be housed in a housing separated from the electromagnet and the microfluidic element holding mechanism.

The mechanism for holding the microfluidic device is arbitrary as long as it holds the microfluidic device at a position where the magnetic fluid filled in the flow path of the microfluidic device can be moved by magnetism generated by a magnet. is there. It is preferable to maintain the positional relationship with the electromagnet with good reproducibility. The holding mechanism may be fixed at a fixed position in the apparatus or movable in the apparatus. It is preferable that the mechanism has a positioning mechanism and a spring for the microfluidic device, and can hold the microfluidic device by one operation.

The fluid transfer device for a microfluidic device according to the present invention has other mechanisms, such as a temperature control mechanism, an optical and other detection mechanism, depending on the purpose of use of the microfluidic device.
It may have a sample injection mechanism, a valve mechanism, a washing mechanism, and the like.

The fluid transfer device of the microfluidic device of the present invention includes, for example, a reaction device such as a microreactor, a PCR (polymerase chain reaction) device; a membrane filtration device, a dialysis device, an electrodialysis device, and a gas. Pretreatment equipment for chemical analysis, such as separation equipment, gas dissolution equipment, and extraction equipment; gene analysis equipment, immunological analysis equipment, gas analysis equipment,
It can be preferably used for a chemical or biochemical analyzer such as a water quality analyzer; a spotter for producing a microarray such as a DNA chip or an immune chip.

[0035]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples. In the following examples and comparative examples, "parts" is "parts by weight".

[Energy Beam Irradiation Apparatus] A light source unit for a multi-light 200 type exposure apparatus manufactured by Ushio Inc. incorporating a 200 w metal halide lamp was used. The UV intensity is 50 mw / cm ² unless otherwise stated.

[Viscosity measuring method] VM manufactured by Yamaichi Electric Co., Ltd.
Room temperature (24 ± 2 ° C) using a -100A type viscometer
Was measured.

[Production Example 1] [Preparation of energy ray-curable composition (i)] The active energy ray-crosslinkable polymerizable compound has an average molecular weight of about 2,000.
Trifunctional urethane acrylate oligomer ("Unidick V-426" manufactured by Dainippon Ink and Chemicals, Inc.)
3 "), 20 parts of 1,6-hexanediol diacrylate (" New Frontier HDDA "manufactured by Daiichi Kogyo Seiyaku Co., Ltd.), and nonylphenoxypolyethylene glycol (n = 17) acrylate (Daiichi Kogyo Seiyaku) "N-177E" manufactured by Co., Ltd .; an amphipathic monomer)
, 20 parts of 1-hydroxycyclohexyl phenyl ketone (“Irgacure 184” manufactured by Ciba Geigy) as a photopolymerization initiator, and 2,4-
0.1 parts of diphenyl-4-methyl-1-pentene (manufactured by Kanto Chemical Co., Ltd.) was uniformly mixed to prepare composition (i).

[Preparation of microfluidic device] 5 cm x 5 cm x polystyrene ("Dick Styrene XC-520" manufactured by Dainippon Ink and Chemicals, Inc.) was used as the substrate (1).
Using a 1 mm plate, the composition (i) was applied thereto using a 127 μm bar coater, and irradiated with 50 mw / cm ² ultraviolet rays for 3 seconds in a nitrogen atmosphere to semi-cure the coating film (2). Was.

On this semi-cured coating film (2), 127 μm
The composition (i) is applied using a bar coater of the type described above, and a photomask is used to apply 50 mw / c to a portion other than the portion that becomes the folded flow path (4) shown in FIG.
m ² ultraviolet rays are irradiated in a nitrogen atmosphere for 3 seconds to semi-cure the irradiated portion of the coating (3), and then the uncured composition (i) of the unirradiated portion of the coating (3) with ethanol. Was washed away, and the shape shown in FIG.
m and a length of 1.5 m (flow channel cross-sectional area 3 × 10 ⁻⁸ m ² , total flow volume of the flow channel 4.5 × 10 ⁻⁸ m ³ ), and a resin-deficient portion to be a flow channel (4) was formed. Forming a coating film (3) and forming a member (A)
And

As the cover (6), polystyrene (Dick Styrene XC-52 manufactured by Dainippon Ink and Chemicals, Inc.) was used.
0 "), a composition (i) was applied thereto using a 127 μm bar coater, and the same ultraviolet ray as used above was used in a nitrogen atmosphere without a photomask. The coating film (5) was semi-cured by irradiating for 3 seconds to obtain a member (B). Next, the coating film (5) in the semi-cured state of the member (B) is brought into close contact with the coating film (3) of the member (A), and is further irradiated with ultraviolet rays for 30 seconds to form a coating film on the coating film (3). (5) and a cover (6) made of a polystyrene plate were adhered, and the resin-deficient portion of the coating film (dendritic layer) (3) was formed as a capillary channel (4).

[Formation of Connection Port] Holes are drilled in the member (B) at positions corresponding to both ends of the flow path (4) with a 3 mm drill, and the inside diameter is 3 mm and the height is 5 mm.
Was bonded to form an inlet (7) and an outlet (8) to obtain a microfluidic device.

[Example 1] Micros obtained in Production Example 1
20 μl (2 × 10 5) from the inlet (7) of the fluidic element ^-8m
³) Of distilled water colored with methylene blue to channel (4)
Introduced. Then, about 1 μl (1 × 10^-9m³) Magnetism
Fluid (Ritile Management, viscosity 400 mPa.
s) was introduced from the inlet (7) into the flow path (4). this
At that time, the magnetic fluid and the colored water were not mixed. Permanent magnet
Inlet (7) from outside the microfluidic device along the flow path
From the outlet to the outlet (8), the magnetic fluid
(4) It moves inside and the colored water is pushed by it and moves
Outflow from exit (8).

Example 2 A magnetic fluid (Ritile Management, viscosity 400 mPa · s) was introduced from the inlet (7) of the microfluidic device obtained in Production Example 1 and filled into the entire flow channel. In (7), distilled water colored with methylene blue was placed. When the electromagnet was placed close to the outlet (8) of the microfluidic device and a current was applied, the magnetic fluid moved in the flow path toward the outlet (8), and when the current was turned off, the magnetic fluid stopped. At this time, the colored water also was drawn by the magnetic fluid and showed a similar movement. Further, by changing the current flowing through the electromagnet, it was possible to control the moving speed of the magnetic fluid and the colored water. Furthermore, when the current flowing through the electromagnet was kept constant, the fluid transfer speed increased when the remaining amount of the magnetic fluid in the flow path became small.However, by controlling the current flowing through the electromagnet, the transfer speed should be kept constant. Was completed.

[0045]

According to the fluid transfer method of the present invention, since it is not necessary to connect a pipe or a wiring for liquid supply to the microfluidic device, it is difficult to connect these devices in terms of dimensions and strength. The structure can be simplified because it is not necessary to form a connection part. Further, it is easy to use in an isolated atmosphere such as a reduced pressure condition, a special gas atmosphere, and a constant temperature or low temperature condition. Further, by controlling the magnetism in terms of current, the transfer speed and the driving force can be easily controlled. Furthermore, for example, when applied to a microchemical device for (bio) chemical synthesis or (bio) chemical analysis,
Very large parallel processing is easy, and when applied to a microarray manufacturing nozzle, the liquid discharge mechanism can be simplified.

[Brief description of the drawings]

FIG. 1 is a schematic plan view of a microfluidic device manufactured in Production Example 1 and used in Examples 1 and 2.

FIG. 2 is a schematic view of an elevation view of a microfluidic device manufactured in Production Example 1 and used in Examples 1 and 2.

[Explanation of symbols]

 1: base material (polystyrene plate) 2: coating film, resin layer 3: coating film, resin layer 4: flow path 5: coating film, resin layer 6: cover (polystyrene plate) 7: inlet 8: outlet

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) G01N 37/00 101 G01N 37/00 101 F term (Reference) 2G052 AA28 AB27 AD02 AD06 AD22 AD26 CA04 HC28 JA07 JA09 3H069 AA01 BB11 CC04 DD42 EE05 EE07 EE32 EE37 EE45 3H075 AA09 CC35 DB08 DB49 EE12 4G075 AA02 AA70 CA42 CA51 DA01 EB23 FB12

Claims (6)

[Claims] 1. A magnetic fluid is introduced into a capillary channel,
A state where there is a portion where the magnetic fluid occupies the entire cross section of the flow path is present, and the magnetic fluid is moved in the flow path direction by applying magnetism from outside the flow path, and the target fluid to be transferred is used as a driving force by the capillary. A fluid transfer method, wherein the fluid is transferred in a flow path in a shape of a circle. 2. A capillary channel having a cross-sectional area of 5 × 10
The fluid transfer method according to claim 1, wherein the flow rate is ⁻¹² m ^{2 to} 5 × 10 ⁻⁶ m ² . 3. The fluid transfer method according to claim 1, wherein the magnetism is provided by an electromagnet. 4. A method in which magnetism moves with time in magnetic field lines,
And / or whose intensity changes over time,
The fluid transfer method according to claim 3. 5. A fluid transfer device for a microfluidic device, using the fluid transfer method according to claim 1. 6. A mechanism for moving a magnet or a magnetic field line along a flow path of a capillary and / or a mechanism for changing the intensity of a magnetic field line, and (3) a micro unit. A fluid transfer device for a microfluidic device, comprising: a mechanism for holding a fluidic device.