JP4500581B2 - Fluid element - Google Patents

Description

  The present invention relates to a liquid element, and more specifically, to a liquid element used in a field that requires manipulation of a small amount of liquid, such as a chemical analyzer, a medical device, or biotechnology. In particular, regarding a small fluid device applied to a miniaturized analysis system (μTAS: Micro Total Analysis System) that performs chemical analysis or chemical synthesis on a chip, removal of blood cell components from blood, mixing of different fluids, and The present invention relates to a fluid element applied to dissolution of solid components, reaction promotion, and the like. In addition, it is applied to a plasma separation operation or the like performed in a therapy for removing a disease-related substance from blood or an apheresis therapy.

  In recent years, with the development of three-dimensional microfabrication technology, attention has been focused on a system that integrates minute flow paths, liquid elements such as pumps and valves, and sensors on a substrate such as glass or silicon, and performs chemical analysis on the substrate. ing. These systems are called miniaturized analysis systems, μ-TAS (Micro Total Analysis System) or Lab on a Chip. By reducing the size of the chemical analysis system, it is possible to reduce the ineffective volume and greatly reduce the amount of the sample.

  In addition, the analysis time can be shortened and the power consumption of the entire system can be reduced. Furthermore, the low price of the system can be expected by downsizing. Since μ-TAS can reduce the size and cost of the system and significantly reduce the analysis time, it can be applied in the medical field such as home medical care and bedside monitor, and in the bio field such as DNA analysis and proteome analysis. Expected.

  There is disclosed a microreactor capable of realizing a series of biochemical experiment operations by mixing and reacting solutions, then performing quantification and analysis, and separating them by combining several cells (see Patent Document 1). . The microreactor has an independent reaction chamber sealed with a flat plate on a silicon substrate. In this reactor, a reservoir cell, a mixing cell, a reaction cell, a detection cell, and a separation cell are combined. By forming a large number of reactors on the substrate, a large number of biochemical reactions can be performed simultaneously in parallel. Furthermore, not only analysis but also substance synthesis reactions such as protein synthesis can be performed on the cell.

  When analyzing blood, it may be necessary to separate formed components such as blood cells from the blood. A centrifuge device is disclosed that is used with a blood bag unit with a leukocyte removal filter (see Patent Document 2).

  Moreover, the method of removing a blood cell component from blood using glass fiber is disclosed (refer patent document 3).

  Further, a method for removing red blood cells using a filter that permeates red blood cells and supplements white blood cells is disclosed (see Patent Document 4).

  Further, a blood cell separation device using a mesh filter is disclosed (see Patent Document 5).

  On the other hand, a chaotic micro mixing device using magnetic particles has been proposed (see Non-Patent Document 1).

In addition, a device that measures the density of a fluid from a change in resonance frequency using MEMS technology has been proposed (see Non-Patent Document 2).
JP 10-337173 A Japanese Patent Application Laid-Open No. 07-0473303 Japanese Patent Laid-Open No. 05-099918 Japanese Patent Application Laid-Open No. 08-104643 JP 2003-207504 A Japan Society of Mechanical Engineers 2002 Annual Conference Performance Materials (VI), September 2002, p. 25-27, Tokyo 1997 IEEE, p278

  Separation of blood cells is an important issue for constructing a system for collecting and analyzing blood. Conventionally, centrifuges for separating blood cell components from blood have been used, but conventional centrifuges have been difficult to integrate on a large and μTAS chip.

  On the other hand, in the field of molecular biology, magnetic particles are used to separate and extract specific cells and DNA from a biomolecule mixed solution. When a technique for separating biomolecules using magnetic particles is integrated on a μTAS chip, mixing (stirring) of magnetic particles becomes an important problem. Since the microscale flow field has an ultra-low Reynolds number (Re << 1), turbulence and separation, which are mixing promotion mechanisms in the microscale, do not occur. In particular, macromolecules such as magnetic particles and biomolecules (diameter of about 1 to 10 μm) have a problem in that mixing becomes inefficient because the effect of molecular diffusion due to Brownian motion becomes extremely small.

  The present invention has been made in view of such a background art, and an object thereof is to provide a novel small fluid element that can be integrated on a μTAS or Lab-on-a-Chip chip.

The present invention has a movable part and a non-movable part connected by a beam on the same substrate, and a fluid chamber in which the movable part introduces a fluid, and a fluid chamber in which the fluid introduced from the flow path exists. And a fluid element characterized in that the beam is torsionally vibrated to give acceleration to the movable part to mix or separate the fluid. .

  The present invention provides a fluidic device that can efficiently separate or mix components in a fluid in a microscale flow.

  The present invention will be specifically described below.

(First embodiment)
FIG. 1 is a diagram showing features of the present invention. 1 is a substrate, 2 is a movable part, 3 is a fluid chamber located in the movable part, 4a-4b are beams or torsion springs connected to the movable part, 9 is an input part for mixed liquid, and 10 is an output of fluid. Part. Reference numeral 5 denotes an input-side flow path arranged on the torsion spring 4a, and 6 denotes an output-side flow path arranged on the torsion spring 4b. Reference numeral 11 denotes torsional vibration caused by a torsion spring, which indicates that periodic angular acceleration is given to the movable part.

  Moreover, 21-22 of FIG. 2 shows the bar magnet arrange | positioned on the back surface of a movable part.

  3 is a side view of the first embodiment, in which 31 is a coil, 32 is a soft magnetic layer, 33 is a coil production board, 34 is a spacer, and 35 is a power source for driving the coil. The coil 31 generates a magnetic field in a direction substantially perpendicular to the surface of the coil creation board, and generates torque about the center of the torsion spring as a rotation axis in the magnet 21-22 placed in the magnetic field.

  That is, the present invention includes a movable portion 2 and a non-movable portion connected to each other in the same substrate 1 by beam portions 4a-4b, and the movable portion 2 includes a flow path 5 and a fluid chamber 3 for introducing fluid. In other words, the fluid element is configured to separate components of the mixed fluid 9 by applying acceleration to the movable portion 2.

Assuming that the moment of inertia of the movable part 2 is I and the spring constant of the torsion spring is k, the resonance angular frequency ω of the movable part 2 is ω = (k / I) ^0.5 , and the resonance frequency f is f = ω / (2π).

  When an AC voltage having a frequency equal to the resonance frequency is applied by the coil driving power source 35, a current flows through the coil, a periodic magnetic field perpendicular to the substrate is generated, and the movable part starts resonance vibration. Here, although the Q value varies depending on the deflection angle in the air, it is about 1000 to several thousands, and is 10,000 or more in vacuum.

In the resonance state, the deflection angle φ is described as φ = φ ₀ sin ωt with respect to time t. However, φ ₀ is the maximum deflection angle. Also, the angular acceleration in the tangential direction of rotation is d ² φ / dt ² = −ω ² φ. In addition, the tangential velocity v at a location r away from the rotation axis is v = rωφ ₀ cosωt. The radial acceleration a at this time is a = v ² / r = rω ² φ ₀ ² cos ² ωt. That is, a centrifugal force of ρa = ρv ² / r = ρrω ² φ ₀ ² cos ² ωt per unit volume acts on a fluid having a density ρ at a position r away from the rotation axis. As can be seen from the equation, this force periodically varies with time, but always has a positive sign, and a fluid component having a higher density is distributed farther from the rotation axis.

  That is, the fluid component can be separated by the centrifugal force generated by the rotation of the fluid chamber 3 arranged in the movable part.

  Human blood has a plasma component of about 55% and a blood cell component of about 45%. About 91% of plasma components are water, about 7% are plasma proteins, and about 0.9% are inorganic salts. Also, about 96% of the blood cell components are red blood cells, about 3% are white blood cells, and about 1% are platelets. The specific gravity of red blood cells is 1.095, the specific gravity of white blood cells is 1.063-1.085, and the specific gravity of platelets is 1.032. The light side can be separated as a plasma component by centrifugation.

  Here, when the resonance frequency f is about 20 kHz and the maximum deflection angle is about 10 degrees, a periodic centrifugal force having a peak of about 5000 G can be obtained at a distance of 0.1 mm from the rotation axis. That is, in the present invention, by utilizing the torsional vibration of a small liquid chamber connected to a minute torsion spring having a flow path, it is possible to easily obtain a high rotational speed, which is similar to a large-sized centrifuge with a small structure. There is an effect that the centrifugal force of can be obtained. Of course, there is an effect that less power is required.

  FIG. 2 is a diagram showing the arrangement of the magnets arranged on the back surface of the movable part 2, and two round bar magnets having a diameter of 211 μm and a length of 0.98 mm are arranged.

  FIG. 3 is a schematic side view of the present embodiment, in which 31 is a coil formed in a thin film shape, 32 is a soft magnetic material, 33 is a substrate on which 32 and 31 are formed, 34 is a spacer, and 35 is A power source for driving the coil.

  In addition, the moment of inertia changes and the natural frequency changes due to the separation, but if the drive frequency is matched to the natural frequency at the time of non-separation, there is an effect that the progress of the separation can be detected from the change of the deflection angle.

  Further, if the power supply frequency is changed according to the change of the natural vibration, it is possible to maintain the vibration, and there is an effect that the degree of separation progress can be detected from the changed frequency.

(Second Embodiment)
FIG. 4 is a diagram illustrating characteristics of the second embodiment. The present embodiment is substantially the same as the first embodiment except that the flow path on the liquid chamber output side has branch channels 41-43.

  In FIG. 4, reference numerals 44 to 46 denote fluid output units. When a mixed fluid containing particles having different specific gravities such as blood is flowed from 9, the fluid is centrifuged in the liquid chamber 3 that rotates in a torsional shape, and is branched by the flow. The fluid reaches 41-43 and is branched. A fluid containing a lot of components having a large specific gravity such as blood cells flows through 44-45, and a component fluid having a low specific gravity such as plasma flows through 46.

  That is, by having the branch flow paths 41-43, there is an effect that components having a large specific gravity can be continuously separated and recovered while continuing to flow the mixed fluid.

(Third embodiment)
FIG. 5 is a diagram illustrating characteristics of the third embodiment.

  51 is a substrate, 52 is a movable part which is a bent spring structure beam, 53 is a fluid chamber located in the movable part, 54 is a comb electrode which is a first electrode, and 55 is a second electrode. It is a comb-type electrode that is an electrode. In the present embodiment, in particular, the non-movable part has the first electrode 54, the movable part has the second electrode 55 facing the first electrode, and the first electrode 54 and the second electrode 54 The electrostatic force between the electrodes 55 is utilized to give acceleration to the movable part to mix the fluid components.

In the resonance state, the displacement x of the movable part is described by x = x ₀ sin ωt with respect to time t. However, _{x 0} is the maximum displacement. At this time, the acceleration a is d ² x / dt ² = −ω ² x. In other words, a fluid having a density ρ has a force of ρa = ρv ² / r = −ρω ² x ₀ sin ωt per unit volume. As can be seen from the equation, this force varies periodically with respect to time and the sign is switched, so that diffusion or mixing of fluid components of different densities is facilitated.

In FIG. 5, 56 and 57 form a Y-shaped channel together with the channel 53. When a fluid such as plasma is flowed through 56 and a fluid containing magnetic particles or the like that can attach only a target molecule to the surface by an antigen-antibody reaction is flowed through 57, if there is no vibration, the microscale flow field is extremely low. Mixing cannot be expected due to the Reynolds number (Re << 1) and the difficulty of diffusion due to Brownian motion due to the size of the particles. In this case, the flow path provided in the movable part is periodically moved in the direction perpendicular to the flow path, and the acceleration in the vertical direction of the flow path is periodically changed including the sign, thereby Among them, there is an effect that even particles that are hardly expected to diffuse due to Brownian motion due to the size can be mixed effectively.

(Fourth embodiment)
FIG. 6 is a diagram illustrating characteristics of the fourth embodiment.

  This embodiment is substantially the same as the first embodiment except that the flow path 61-62 that is easy to flow in a specific direction is connected to the flow path 5-6 or the liquid chamber 3.

  Since the volume of the flow path 5-6 or the liquid chamber 3 is slightly changed by twisting, if the flow paths 61-62 that are easy to flow in a specific direction are connected, the substantial flow in the specific direction is caused by torsional vibration. This produces an effect of generating a pump function. Here, the flow path that easily flows in a specific direction may be a flow path including a valve element that opens a valve in a certain direction and closes the valve in a reverse direction.

(Fifth embodiment)
FIG. 7 is a diagram illustrating characteristics of the fifth embodiment.

  In FIG. 7, reference numerals 71 and 72 denote torsion springs that provide two movable axes. In the present embodiment, in particular, there are two or more movable axes or two or more movable directions, and the angular velocity is controlled in a desired direction. It is characterized by that. Since the angular velocity can be controlled in a desired direction, it can be used for various purposes such as separation and mixing as needed, and there is an effect that it can have a function as a flask in a microscale.

It is the schematic which shows the 1st Embodiment of this invention. It is the schematic which shows arrangement | positioning of the magnet of 1st Embodiment. It is a schematic diagram which shows the side view of 1st Embodiment. It is the schematic which shows the 2nd Embodiment of this invention. It is the schematic which shows the 3rd Embodiment of this invention. It is the schematic which shows the 4th Embodiment of this invention. It is the schematic which shows the 5th Embodiment of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Board | substrate 2 Movable part 3 Liquid chamber 4a-4b Torsion spring structure beam 5-6 Flow path 9 Fluid input part 10 Fluid output part 11 Torsion rotation 21-22 Magnet 31 Coil 32 Soft magnetic layer 34 Spacer 35 Coil drive 41-43 Branch channel 44-45 Fluid output unit 51 Substrate 52 Bent spring structure beam movable unit 53 Channel provided in bent type spring structure beam movable unit 54 Movable unit side comb electrode (first electrode)
55 Non-movable part side comb electrode (second electrode)
56-57 Y-shaped flow path constituting flow path 61-62 A flow path that easily flows in a specific direction 71-72 A torsion spring structure beam that provides biaxial rotation

Claims (6)

A movable part and a non-movable part connected by a beam are provided on the same substrate, and the flow path for introducing the fluid by the movable part and a fluid chamber in which the fluid introduced from the flow path exists are provided. A fluid element, wherein the beam is torsionally vibrated to give acceleration to the movable portion to mix or separate the fluid.   The fluid element according to claim 1, wherein an acceleration is applied to the movable part using electromagnetic force.   The fluid element according to claim 1, wherein an acceleration is applied to the movable part using an electrostatic force. The fluid element according to claim 1, wherein the flow path on the output side of the fluid chamber is a branched flow path.   The fluid element according to claim 1, wherein the flow path further includes means for flowing the fluid in a specific direction. The fluid element according to claim 1, wherein there are a plurality of the movable parts, and the fluid is mixed or separated by controlling an angular velocity of the plurality of movable parts.

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