JP2016203157A - Droplet formation device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a droplet formation device capable of restraining a variation in the number of settleable particles included in a discharged droplet.SOLUTION: This droplet formation device comprises a liquid holding part for holding a solution including a settleable particle, a film-like member having a nozzle and vibrating to discharge the solution held by the liquid holding part as a droplet from the nozzle, excitation means for vibrating the film-like member and driving means for selectively imparting a discharge waveform for forming the droplet by vibrating the film-like member and an agitation waveform for vibrating the film-like member in a range of not forming the droplet, to the excitation means.SELECTED DRAWING: Figure 7

Description

  The present invention relates to a droplet forming apparatus.

  2. Description of the Related Art Conventionally, a droplet forming apparatus that discharges liquid held in a liquid chamber as droplets is known. In a conventional droplet forming apparatus, for example, a dispersion liquid using a pigment as a colorant is used as a liquid to be discharged.

  However, in a dispersion liquid using a pigment as a colorant, the pigment does not settle by itself, but when left in a droplet forming apparatus for a long time, due to the cohesive force derived from van der Waals force and the like, In some cases, the pigment aggregated and settled. When the aggregate of the pigment settles, the nozzle is clogged and the liquid cannot be ejected stably. Therefore, the liquid is redispersed to prevent the aggregation of the pigment (see, for example, Patent Document 1).

  By the way, in recent years, with the progress of the stem cell technology, development of a technology for forming a tissue body by ejecting a plurality of cells by inkjet has been performed. Cells are sedimenting particles that settle when left for a long time. Precipitating particles such as cells have a diameter about 100 times that of particles (pigments etc.) ejected by conventional droplet forming apparatuses and are heavy. The settleable particles of the particles settle even in a single state that is not agglomerated.

  For this reason, it is difficult to sufficiently stir the solution containing the sedimenting particles by the same method as that of the conventional droplet forming apparatus, and the droplets are included in the ejected droplets due to the sedimentation of the sedimenting particles. There is a concern that the number of settleable particles varies.

  The present invention has been made in view of the above points, and an object of the present invention is to provide a droplet forming apparatus capable of suppressing variation in the number of sedimentation particles contained in a discharged droplet. .

  The droplet forming apparatus is a film-like device in which a liquid holding unit that holds a solution containing settling particles and a nozzle are formed, and the solution held in the liquid holding unit is ejected as droplets from the nozzle by vibration. Member, vibration means for vibrating the film-shaped member, discharge waveform for vibrating the film-shaped member to form the droplet, and stirring waveform for vibrating the film-shaped member in a range where the liquid droplet is not formed And a driving means for selectively applying to the vibration means.

  According to the disclosed technology, it is possible to provide a droplet forming apparatus capable of suppressing variation in the number of sedimentation particles contained in the ejected droplets.

It is sectional drawing which illustrates the droplet formation apparatus which concerns on 1st Embodiment. It is a figure (the 1) explaining unevenness of particles. It is a figure explaining the countermeasure of the deviation of a particle. It is a figure which illustrates the process in which a droplet is formed. It is FIG. (1) explaining a difference with the conventional droplet forming apparatus. It is FIG. (2) explaining a difference with the conventional droplet formation apparatus. It is a figure which illustrates the stirring waveform and discharge waveform which a drive device produces | generates. It is a figure explaining the natural vibration mode of the disk to which the periphery was fixed. FIG. 3 is a diagram (part 1) illustrating a suitable agitation waveform generated by a drive device; It is a figure explaining the natural vibration mode of the rectangular board by which the periphery was fixed. It is a figure explaining the natural vibration mode of the slit-shaped board by which both ends were fixed. It is a figure which illustrates the fundamental natural frequency of a droplet formation device. FIG. 6 is a diagram (part 2) illustrating a suitable stirring waveform generated by the drive device; It is a figure explaining the stirring waveform from which a drive voltage differs. It is a figure explaining the area | region which implements stirring using the stirring waveform of FIG. It is a figure explaining the method of vibrating a member larger than a membrane. It is sectional drawing which illustrates the droplet formation apparatus which concerns on the modification 3 of 1st Embodiment. FIG. 6 is a diagram (part 3) illustrating a suitable agitation waveform generated by the drive device; It is a figure explaining the observation apparatus used in the Example. It is FIG. (2) explaining the bias | inclination of particle | grains. It is a figure explaining the stirring waveform and discharge waveform which were used in the Example.

  Hereinafter, embodiments for carrying out the invention will be described with reference to the drawings. In the drawings, the same components are denoted by the same reference numerals, and redundant description may be omitted.

<First Embodiment>
[Structure of droplet forming apparatus]
First, the droplet forming apparatus according to the first embodiment will be described. FIG. 1 is a cross-sectional view illustrating a droplet forming apparatus according to the first embodiment. Referring to FIG. 1, the droplet forming device 10 includes a liquid chamber 11, a membrane 12, a piezoelectric element 13, and a driving device 30. FIG. 1 schematically shows a state in which the solution 300 containing the sedimentable particles 350 is held in the liquid chamber 11.

  In the present embodiment, for convenience, the liquid chamber 11 side is the upper side, and the piezoelectric element 13 side is the lower side. Further, the surface on the liquid chamber 11 side of each part is the upper surface, and the surface on the piezoelectric element 13 side is the lower surface. The planar view refers to viewing the object from the normal direction of the upper surface of the membrane 12, and the planar shape refers to the shape of the object viewed from the normal direction of the upper surface of the membrane 12.

  In the droplet forming apparatus 10, the liquid chamber 11 is a liquid holding unit that holds the solution 300 containing the settling particles 350 (in which the settling particles 350 are dispersed), and is formed from, for example, metal, silicon, ceramic, or the like. can do. The liquid chamber 11 has an air release portion 111 that opens the inside of the liquid chamber 11 to the atmosphere, and is configured so that bubbles mixed in the solution 300 can be discharged from the air release portion 111.

  The membrane 12 is a film-like member fixed to the lower end portion of the liquid chamber 11. A nozzle 121, which is a through hole, is formed at the approximate center of the membrane 12, and the solution 300 held in the liquid chamber 11 is discharged as a droplet from the nozzle 121 by the vibration of the membrane 12. The planar shape of the membrane 12 can be a circle, for example, but may be an ellipse or a rectangle.

  Since the peripheral edge portion of the membrane 12 is fixed to the lower end portion of the liquid chamber 11, the amplitude of vibration is smaller in the outer peripheral portion of the membrane 12 constituting the bottom surface of the liquid chamber 11 than in the central portion. Therefore, as shown in FIG. 2, when the settleable particles 350 are settled, they tend to accumulate on the outer peripheral portion of the membrane 12 constituting the bottom surface of the liquid chamber 11. In FIG. 2, the upper side of the arrow indicates a state before the membrane 12 is vibrated, and the lower side of the arrow indicates a state after the membrane 12 is vibrated.

  FIG. 3 is a diagram illustrating a method for improving the settling particle bias. In FIG. 3A, the cross-sectional shape on the inner wall side of the lower end portion of the liquid chamber 11 is a curved shape. In FIG.3 (b), the cross-sectional shape of the outer peripheral part of the membrane 12 is made into the curved shape. As shown in FIG. 3, by providing a curved portion that increases in thickness as it approaches the edge of the bottom surface at the outer peripheral portion of the bottom surface in the liquid chamber 11, the settleable particles 350 settle and the bottom surface in the liquid chamber 11. It is possible to improve the tendency to accumulate on the outer periphery of the.

  The material of the membrane 12 is not particularly limited. However, if the membrane is too soft, the membrane 12 vibrates easily, and it is difficult to suppress vibration immediately when it is not discharged. . As a material of the membrane 12, for example, a metal material, a ceramic material, a polymer material having a certain degree of hardness, or the like can be used. In particular, a material having low adhesion to the sedimentation particles 350 is preferable.

  Cell adhesion is generally said to be dependent on the contact angle of the material with water. When the material is highly hydrophilic or highly hydrophobic, the cell adhesion is low. Various metal materials and ceramics (metal oxides) can be used as the highly hydrophilic material, and fluorine resin or the like can be used as the highly hydrophobic material.

  Examples of such materials include stainless steel, nickel, aluminum and the like, silicon dioxide, alumina, zirconia and the like. In addition, it is conceivable to reduce cell adhesion by coating the surface of the material, such as coating the surface of the material with the aforementioned metal or metal oxide material, or a synthetic phospholipid polymer that mimics the cell membrane (eg, It is also possible to coat by Lipidure, manufactured by Yuru Co.

  The nozzle 121 is preferably formed as a substantially circular through hole substantially at the center of the membrane 12. In this case, the diameter of the nozzle 121 is not particularly limited. However, in order to avoid the sedimentation particles 350 from being clogged with the nozzle 121, it is preferable that the diameter be equal to or larger than twice the size of the sedimentation particles 350.

  The piezoelectric element 13 is formed on the lower surface side of the membrane 12. The shape of the piezoelectric element 13 can be designed according to the shape of the membrane 12. For example, when the planar shape of the membrane 12 is circular, it is preferable to form the piezoelectric element 13 having an annular shape (ring shape) around the nozzle 121.

  The piezoelectric element 13 has, for example, a structure in which electrodes for applying a voltage are provided on the upper surface and the lower surface of a piezoelectric material. By applying a voltage to the upper and lower electrodes of the piezoelectric element 13, a compressive stress is applied in the lateral direction of the paper surface and the membrane 12 can be vibrated. As the piezoelectric material, for example, lead zirconate titanate can be used. In addition, various piezoelectric materials such as bismuth iron oxide, metal niobate, barium titanate, or a material obtained by adding a metal or a different oxide to these materials can be used.

  However, the vibration means for vibrating the membrane 12 is not limited to the piezoelectric element 13. For example, it is possible to vibrate the membrane 12 using the difference in linear expansion coefficient by applying a material having a different linear expansion coefficient from the membrane 12 on the membrane 12 and heating the material. At this time, it is preferable that the heater is formed on materials having different linear expansion coefficients, and the membrane 12 is vibrated by heating the heater by energization.

  The driving device 30 is a driving unit that drives the piezoelectric element 13. The driving device 30 selectively applies (for example, alternately) a discharge waveform for vibrating the membrane 12 to form a droplet and a stirring waveform for vibrating the membrane 12 in a range where no droplet is formed. can do.

  That is, the drive device 30 can discharge the solution 300 held in the liquid chamber 11 as droplets from the nozzle 121 by adding a discharge waveform to the piezoelectric element 13 and controlling the vibration state of the membrane 12. Further, the drive device 30 can stir the solution 300 held in the liquid chamber 11 by applying a stirring waveform to the piezoelectric element 13 and controlling the vibration state of the membrane 12. Note that no droplets are discharged from the nozzle 121 during stirring.

  In this way, by stirring while the droplets are not formed, the settling particles 350 contained in the solution 300 are prevented from being settled and aggregated on the membrane 12 while the droplets are not formed. Can do. As a result, it is possible to suppress clogging of the nozzles 121 and variations in the number of the settling particles 350 in the discharged droplets.

  In the solution 300 containing the sedimentation particles 350, the sedimentation particles 350 are metal microparticles, inorganic microparticles, or cells, particularly human-derived cells. Although it does not specifically limit and can be used as a metal microparticle, Silver particle | grains, a copper particle, etc. can be used, These can be used for the use which draws wiring by the discharged droplet.

  Also, the inorganic fine particles are not particularly limited, and titanium oxide, silicon oxide or the like is used for white ink or spacer material coating. Further, it is preferable to use animal cells, particularly human-derived cells, as the cells, and the droplet forming device 10 can be used as a cell discharge device for forming a tissue piece for evaluation of medicinal properties and cosmetics. .

  The solvent of the solution 300 is most commonly water, but is not limited thereto, and various organic solvents such as alcohol, mineral oil, and vegetable oil can be used. When water is used as the solvent, it is preferable that a wetting agent for suppressing evaporation of moisture and a surfactant for reducing surface tension are included. For these formulations, it is possible to use very common materials used for inkjet inks.

  The amount of the solution 300 held in the liquid chamber 11 is not particularly limited, but it is typically possible to hold a liquid amount of about 1 μl to 1 ml. In particular, when an expensive liquid such as a cell suspension is used, it is preferable that droplets can be formed with a small amount of liquid, and therefore, a configuration capable of holding a liquid volume of about 1 μl to 50 μl is preferable.

[Droplet formation process of droplet formation device]
Next, a process of forming droplets by the droplet forming apparatus according to the first embodiment will be described. FIG. 4 is a diagram illustrating a process in which droplets are formed. FIG. 4A schematically shows a state when the solution 300 containing the settleable particles 350 is placed in the liquid chamber 11 and left to stand. In the stage of FIG. 4A, the sedimentary particles 350 are in a state of sedimenting at the bottom of the liquid chamber 11.

  When the droplet forming operation is performed in the state of FIG. 4A, the sedimentation particles 350 are aggregated in the vicinity of the nozzle 121, so that a problem that the droplets are not formed may occur. Even if droplets are formed, there is a large variation in the number of sedimentary particles 350 contained in the droplets, such as a supernatant liquid being ejected after a large amount of sedimentary particles 350 is initially ejected. May occur.

  FIG. 4B schematically shows the stirring state of the sedimentary particles 350 when a stirring waveform is input from the driving device 30 to the piezoelectric element 13 and the membrane 12 is slightly vibrated to such an extent that droplets are not formed. Yes. The liquid level in the vicinity of the nozzle 121 is greatly vibrated by the slight vibration of the membrane 12, thereby generating convection as indicated by an arrow A and stirring of the solution 300 containing the sedimentable particles 350 occurs.

  FIG. 4C schematically shows a state in which the ejection waveform is input from the driving device 30 to the piezoelectric element 13 and the droplet 310 is formed by the vibration of the membrane 12. 4B, the sedimentation particles 350 in the liquid chamber 11 are dispersed, and then the ejection waveform is applied from the driving device 30 to the piezoelectric element 13 in FIG. The droplets 310 can be formed while keeping the number of the conductive particles 350 uniform.

  The droplet forming apparatus 10 can efficiently stir the sedimentary particles 350 as compared with the conventional droplet forming apparatus. This will be described in detail with reference to FIGS. 5 and 6.

  FIG. 5 is a diagram (No. 1) for explaining a difference from a conventional droplet forming apparatus. FIG. 6 is a diagram (No. 2) for explaining a difference from the conventional droplet forming apparatus.

  In the conventional droplet forming apparatus 600 shown in FIG. 5A, the piezoelectric element 630 is formed on the upper side or the side surface side of the liquid chamber 610. In the droplet forming apparatus 600, the piezoelectric element 630 is finely vibrated as indicated by a solid line arrow to give kinetic energy to the sedimentary particles 650 via the dispersion in the liquid chamber 610, and in the vicinity of the nozzle 621 and the flow path 620. The settled particles 650 that settled and aggregated in the same manner were dispersed as indicated by broken arrows.

  At this time, as shown in FIG. 6, the movement of one settling particle 650 is a minute vibration. Accordingly, each sedimentation particle 650 in the entire liquid chamber 610 vibrates on the spot, and the sedimentation particles 650 that have settled and aggregated can be dispersed, but the sedimentation particles 650 are agitated. I can't.

  That is, in the method of applying kinetic energy to the sedimentation particles 650 via the dispersion liquid as in the droplet forming apparatus 600, the sedimentation particles 650 are not uniformly stirred in the liquid chamber, but in the liquid chamber 610. The distribution of the settleable particles 650 is generated. For this reason, there is a concern that the number of the settling particles 650 contained in the discharged droplets varies.

  On the other hand, in the droplet forming apparatus 10 shown in FIG. 5B, the piezoelectric element 13 is formed below the membrane 12 where the nozzle 121 is located. Therefore, when the piezoelectric element 13 vibrates as indicated by a solid line arrow, the membrane 12 similarly vibrates as indicated by a solid line arrow, and a flow from the lower direction to the upper direction of the liquid chamber 11 can be generated.

  At this time, as shown in FIG. 6, the movement of one settling particle 350 is a movement from the bottom to the top, and the convection indicated by the arrow A is generated in the entire liquid chamber 11 to contain the settling particles 350. Stirring of the solution 300 to occur. In other words, the flow from the lower direction to the upper direction of the liquid chamber 11 causes the sedimentary particles 350 to be uniformly dispersed inside the liquid chamber 11, thereby suppressing variation in the number of cells in the discharged droplets. Become.

  Further, when the membrane 12 under the droplet forming apparatus 10 vibrates, it is possible to directly give kinetic energy to the sedimentary particles 350 that have settled in the liquid chamber 11 without using a dispersion liquid. Therefore, the sedimentary particles 350 can be efficiently stirred.

  The droplet forming apparatus 600 and the droplet forming apparatus 10 are greatly different in the frequency for vibrating the piezoelectric element. In the droplet forming apparatus 600, the frequency at which the piezoelectric element 630 is vibrated is about 100 kHz.

  On the other hand, in the droplet forming apparatus 10, the frequency at which the piezoelectric element 13 is vibrated during stirring is about 20 kHz. The reason why the frequency of the droplet forming device 10 is lower than the frequency of the droplet forming device 600 is that the sedimentation particles 350 (cells, etc.) are about 100 times as large as the sedimentation particles 650 (pigments, etc.) and heavy. This is because it needs to move slowly and greatly.

FIG. 7 is a diagram illustrating a stirring waveform and a discharge waveform generated by the driving device. FIG. 7 shows an example in which the stirring waveform 31 and the discharge waveform 32 are both rectangular waves, and the pulse waveform 32 is input for one pulse after the pulse train is input as the stirring waveform 31 for a predetermined time. By making the drive voltage V ₁ of the stirring waveform 31 lower than the drive voltage V ₂ of the ejection waveform 32, the droplet 310 is not formed by the application of the stirring waveform 31.

  As described above, the droplet forming apparatus 10 according to the first embodiment performs both stirring and discharging by controlling the vibration of the membrane 12. Thereby, it is possible to disperse the solution 300 containing the settleable particles 350 evenly, thereby suppressing variation in the number of the settleable particles 350 in the formed droplets 310, and at the same time, preventing the nozzle 121 from being clogged. As a result, the solution 300 containing the settleable particles 350 can be stably discharged as droplets 310 continuously for a long time.

<Variation 1 of the first embodiment>
In the first modification of the first embodiment, an example of a suitable stirring waveform is shown. In the first modification of the first embodiment, the description of the same components as those of the already described embodiments may be omitted.

  It is known that the vibration of a disk whose periphery is fixed like the membrane 12 has a plurality of natural vibration modes. For example, “Machine vibration, Watari thickness, Maruzen, p62-65” which is a non-patent reference. Details are described in (hereinafter referred to as Non-Patent Reference 1).

  According to this, the natural frequency fns of the disk can be expressed as n is the number of nodal diameters and s is the number of nodal circles.

  FIG. 8 is a diagram for explaining the natural vibration mode of a disk whose periphery is fixed. In the natural frequency fns, the vibration of the disk when n is 0 to 3 and s is 1 to 3. The mode is shown schematically. In FIG. 8, the outer circle represents a disk, and the inner boundary line represents a node. Adjacent areas separated by nodes are areas where the phase is inverted and vibrates.

  Here, when n = 0 and s = 1, the fundamental mode of vibration of the disc is defined, and the other vibration modes are defined as higher-order modes. As is clear from FIG. 8, there is no node in the disk only when vibrating in the fundamental mode. Table 1 shows the natural frequency fns of the higher-order mode when the natural frequency f01 of the basic mode is 1. According to this, a secondary vibration mode (natural frequency f11) appears in a frequency region about twice or more that of the fundamental mode.

撹拌波形を入力してメンブレン１２の振動による撹拌を行う際に、メンブレン１２の高次モードが励起されるとメンブレン１２の面内において振動強度の分布が生じ、沈降性粒子３５０の存在量に偏りが生じるおそれがある。この場合には、撹拌しないときよりは均一性が増すものの、液滴３１０中の沈降性粒子３５０の数には依然としてばらつきが生じてしまう。

When the stirring waveform is input and stirring is performed by vibration of the membrane 12, if the higher-order mode of the membrane 12 is excited, a vibration intensity distribution is generated in the plane of the membrane 12, and the amount of sedimentation particles 350 is biased. May occur. In this case, although the uniformity is increased as compared with the case where stirring is not performed, the number of settleable particles 350 in the droplets 310 still varies.

  For example, when the rectangular wave described with reference to FIG. 7 is input, if the frequency at which the rectangular wave is input is close to the value of the natural frequency of the higher order mode, the higher order mode is excited. Even if the frequency of the rectangular wave is smaller than the natural frequency of the higher-order mode, the higher-order mode may be excited by the edge of the rectangular wave because the edge of the rectangular wave is steep. .

  Therefore, as shown in FIG. 9, the agitation waveform is composed of a signal in a lower frequency region than the natural frequency of the higher-order mode of the membrane 12, that is, a waveform not including the natural frequency of the higher-order mode. It is preferable. FIG. 9A shows a sine wave composed only of a specific frequency component, and the frequency (= 1 / T) is set to a value smaller than the secondary natural frequency f11.

  Another example of a suitable stirring waveform is shown in FIG. FIG. 9B shows a waveform obtained by low-pass filtering the rectangular wave shown in FIG. 7 at a frequency lower than the secondary natural frequency f11. The waveform does not include the natural frequency component of the higher-order mode. is there. The stirring waveform is not limited to this, and any waveform obtained by cutting the natural frequency component of the higher-order mode may be used.

  From Non-Patent Reference 1, the natural frequency f01 of the fundamental mode is expressed by the following equation (Equation 1).

ここで、ｔはメンブレン１２の厚み、ｒはメンブレン１２の半径（固定部よりも内側の半径）、ρはメンブレン１２の材質の密度、Ｅ及びσはメンブレン１２の材質のヤング率及びポアソン比である。

Here, t is the thickness of the membrane 12, r is the radius of the membrane 12 (radius inside the fixed portion), ρ is the density of the material of the membrane 12, E and σ are Young's modulus and Poisson's ratio of the material of the membrane 12. is there.

  From the equation (Equation 1) and Table 1, it is possible to predict in advance the natural frequency of the fundamental mode of the membrane 12 and the natural frequency of the higher-order mode. However, this is a value in the air, and the natural frequency changes when the liquid is filled on one side as in the method of use in the present embodiment.

  As will be described later, this natural frequency varies depending on the amount of liquid (see FIG. 12 described later). However, the approximate value of the natural frequency can be calculated by the following equation (Equation 2) according to Non-Patent Reference 2, for example. Here, Non-Patent Reference 2 is ““ Vibration of Circular Membranes in Contact with Water ”, Journal of Sound and Vibration 178 (5), 688-690 (1994)”.

ここで、ｆｗ０１は片側に液が接触しているときの基本モードの固有振動数であり、ρｗは水の密度、ΓはＮＡＶＭＩ係数と呼ばれる定数である。ｆ０１のとき、Γは０．７４６３１３であることが知られている。例えば、メンブレン１２として、径１０ｍｍ程度（固定部よりも内側の径）、厚み５０μｍ程度のＳＵＳを用いたとき、ｆｗ０１はｆ０１のおおよそ３０％になる。

Here, fw01 is the natural frequency of the fundamental mode when the liquid is in contact with one side, ρw is the density of water, and Γ is a constant called the NAVMI coefficient. At f01, Γ is known to be 0.746313. For example, when the membrane 12 is SUS having a diameter of about 10 mm (diameter inside the fixed portion) and a thickness of about 50 μm, fw01 is approximately 30% of f01.

  Further, if the same calculation is performed with reference to the NAVMI coefficient of Non-Patent Reference 2, it can be seen that the high-order mode takes a value of approximately 45% to 60% in the air in water.

  In this way, by constructing the agitation waveform from signals in a lower frequency region than the natural frequency of the higher-order mode of the membrane 12, the distribution of vibration intensity in the surface of the membrane 12 is eliminated, and unevenness in agitation is suppressed. Can do.

  The case where the membrane 12 is a disk with a fixed periphery has been described above, but the membrane 12 may be a rectangular plate with a fixed periphery. It is known that the vibration of a rectangular plate with a fixed periphery has a plurality of natural vibration modes as in the case of a circular plate, and the natural frequency fjk is defined as j and k as the number of nodal lines in the vertical and horizontal directions, respectively. Can be expressed.

  FIG. 10 is a diagram for explaining the natural vibration mode of a rectangular plate whose periphery is fixed. In the natural frequency fjk, the vibration of the rectangular plate when j is a value of 1 to 3 and k is a value of 1 to 3. The mode is shown schematically. In FIG. 10, the outer periphery represents a rectangular plate, and the inner boundary line represents a node. Adjacent areas separated by nodes are areas where the phase is inverted and vibrates.

  Here, when j = 1 and k = 1, the fundamental mode of vibration of the rectangular plate is defined, and the other vibration modes are defined as higher-order modes. As is clear from FIG. 10, there is no node in the rectangular plate only when vibrating in the fundamental mode.

  From Non-Patent Document 1, the natural frequency f11 of the fundamental mode is expressed by the equation (Equation 3).

ここで、ｌ、ｍ、ｔはそれぞれメンブレンの縦の長さ、横の長さ、厚み、ρはメンブレン１２の材質の密度、Ｅ及びσはメンブレン１２の材質のヤング率及びポアソン比である。

Here, l, m, and t are the vertical length, horizontal length, and thickness of the membrane, respectively, ρ is the density of the material of the membrane 12, and E and σ are the Young's modulus and Poisson's ratio of the material of the membrane 12.

  From the equation (Equation 3) and FIG. 10, it is possible to predict in advance the natural frequency of the fundamental mode of the membrane 12 and the natural frequency of the higher-order mode.

  Further, the membrane 12 may be a slit-like plate having both ends fixed. It is known that the vibration of the slit plate fixed at both ends has a plurality of natural vibration modes, and the vibration of the slit plate extremely long in one direction is not a two-dimensional direction, but only a one-dimensional direction. Can be considered. The natural frequency fi can be expressed as i as the number of antinodes.

  FIG. 11 is a diagram for explaining the natural vibration mode of the slit plate with both ends fixed, schematically showing the vibration mode of the slit plate when i is a value of 1 to 3 at the natural frequency fi. Yes. Here, when i = 1, it is defined as a fundamental mode of vibration of the slit-shaped plate, and other vibration modes are defined as higher-order modes. As is apparent from FIG. 11, only when vibrating in the basic mode, there are no nodes other than the fixed ends.

  From Non-Patent Document 1, the natural frequency f1 of the fundamental mode is expressed by the equation (Equation 4).

ここで、ｌはメンブレン１２の長さ、Ａ及びＪはメンブレン１２の断面積及び断面２次モーメント、ρはメンブレン１２の材質の密度、Ｅはメンブレン１２の材質のヤング率である。

Here, l is the length of the membrane 12, A and J are the cross-sectional area and second moment of the cross section of the membrane 12, ρ is the density of the material of the membrane 12, and E is the Young's modulus of the material of the membrane 12.

  From the equation (Equation 4) and FIG. 11, it is possible to predict in advance the natural frequency of the fundamental mode of the membrane 12 and the natural frequency of the higher-order mode.

  Therefore, when the membrane 12 is a rectangular plate having a fixed periphery or a slit-shaped plate having both ends fixed, as in the case where the membrane 12 is a circular plate having a fixed periphery, a stirring waveform is applied to the membrane 12. By using a signal in a lower frequency region than the natural frequency of the higher-order mode, the distribution of vibration intensity in the surface of the membrane 12 can be eliminated, and uneven stirring can be suppressed.

<Modification 2 of the first embodiment>
Modification 2 of the first embodiment shows another example of a suitable stirring waveform. In the second modification of the first embodiment, the description of the same components as those of the already described embodiment may be omitted.

  The frequency (= 1 / T) of the stirring waveform shown in FIGS. 9A and 9B can be matched with the natural frequency of the fundamental mode of the membrane 12. At this time, the membrane 12 can be moved with a very low driving voltage, and the stirring state of the settleable particles 350 is not uneven, so that the highest stirring effect can be obtained most efficiently.

  However, the natural frequency of the membrane 12 shifts depending on the amount of the solution 300 held in the liquid chamber 11. FIG. 12 shows, as an example, the result of measuring the natural frequency of the fundamental mode of the prototype droplet forming apparatus using a laser Doppler vibrometer (LV-1710, manufactured by Ono Sokki Co., Ltd.). In the prototype droplet forming apparatus, a ring-shaped push-type piezoelectric element (manufactured by Fuji Ceramics, material C-2) is used as the piezoelectric element 13, and a SUS pinhole (Edmond Optics, Inc.) having a nozzle diameter of 35 μm is used as the membrane 12. Made).

  In FIG. 12, (1) has a liquid volume of 50 μl, (2) has a liquid volume of 40 μl, (3) has a liquid volume of 30 μl, (4) has a liquid volume of 20 μl, (5 ) Shows the case where the amount of liquid retained is 10 μl, and (6) shows the case where the amount of liquid retained is 0 μl (no liquid).

  As is clear from FIG. 12, the natural frequency of the fundamental mode is about 40% smaller while the amount of liquid to be retained changes from 10 μl ((5) in FIG. 12) to 50 μl ((1) in FIG. 12). Become. Considering the amount of liquid that decreases due to droplet formation and the amount of liquid that decreases due to drying, it is difficult to keep the agitation waveform completely matched with the natural frequency of the fundamental mode.

  Therefore, the stirring waveform is a signal in which the frequency is changed from a predetermined first frequency to a second frequency different from the first frequency, and the change range of the natural frequency of the fundamental mode depending on the liquid amount is the first. It is preferable to be included between the second frequency and the second frequency. Thus, even if the natural frequency of the fundamental mode changes depending on the liquid volume, the changed natural frequency of the fundamental mode always exists between the first frequency and the second frequency. 12 can be efficiently vibrated at the natural frequency of the fundamental mode.

  FIG. 13 schematically shows an example of an agitation waveform in which the frequency is changed from the first frequency to the second frequency. Actually, a larger number of waves are formed, and the waveform changes substantially continuously from the first frequency f1 (= 1 / T1) to the second frequency f2 (= 1 / T2).

  In FIG. 13, the sine wave is a continuously modulated signal. However, the signal is not limited to a sine wave, and a low-pass filtered rectangular wave or triangular wave can be used. It is also possible to switch and add a plurality of frequencies step by step. Further, the same agitation effect can be obtained even with a certain type of beat signal in which a plurality of frequency components are added together instead of the waveform obtained by sweeping the frequency.

  Thus, it is preferable that the stirring waveform includes the natural frequency of the fundamental mode of the membrane 12, thereby enabling effective stirring with less energy.

  Further, if the stirring waveform is a signal obtained by changing the first frequency to the second frequency, and the natural frequency of the fundamental mode of the membrane 12 always exists between the first frequency and the second frequency, Is preferred. In this case, even if the natural frequency of the membrane 12 changes depending on the amount of liquid in the liquid chamber 11, stirring can be performed stably.

As a method of uniformly stirring the liquid chamber, as shown in FIG. 14, the voltage is higher than that of the first stirring waveform 31A apart from the first stirring waveform 31A that vibrates the membrane 12 in a range where no droplet is formed. You may stir using the 2nd stirring waveform 31B. In FIG. 14, since the drive voltage V ₄ of the second stirring waveform 31B is higher than the driving voltage V _{3 of} the first stirring waveform 31A, the membrane 12 vibrates more strongly, and the inside of the liquid chamber 11 is stirred more uniformly. It becomes possible to do.

  On the other hand, since the vibration of the membrane 12 is strong, there is a possibility that droplets other than the intended purpose may be formed. Therefore, when stirring using the second stirring waveform 31B, as shown in FIG. 15A, the droplet forming apparatus 10 is used to prevent droplets other than the target from being dropped on the drawing region E1. It is preferable to carry out stirring after moving to the non-drawing region E2. In this case, there is no problem even if a droplet 310 other than the intended one is dropped on the non-drawing region E2. In addition, when stirring using the 1st stirring waveform 31A, as shown in FIG.15 (b), you may implement stirring in the state in which the droplet forming apparatus 10 exists on the drawing area | region E1.

  A method of stirring using a natural frequency of a member larger than the membrane 12 is also suitable. By vibrating a member larger than the membrane 12, it is possible to improve the tendency of the settleable particles 350 to settle and accumulate on the outer peripheral portion of the bottom surface in the liquid chamber 11, and to uniformly agitate the liquid chamber.

  For example, as shown in FIG. 16, the wall portion constituting the liquid chamber 11 may be made thicker than the membrane 12 and the wall portion constituting the liquid chamber 11 may be vibrated. In this case, since the wall part which comprises the liquid chamber 11 vibrates like A of FIG. 16, the center part and outer peripheral part of the membrane 12 exposed in the liquid chamber 11 vibrate to the same extent, and sedimentation is carried out to an outer peripheral part. The tendency for the particles 350 to easily collect can be improved. For comparison, FIG. 16B shows a vibration image when only the membrane 12 is vibrated without vibrating the wall portion constituting the liquid chamber 11.

<Modification 3 of the first embodiment>
In the third modification of the first embodiment, an example of a droplet forming apparatus provided with a liquid amount detection unit is shown. Note that in the third modification of the first embodiment, the description of the same components as those of the already described embodiments may be omitted.

  FIG. 17 is a cross-sectional view illustrating a droplet forming apparatus according to Modification 3 of the first embodiment, and illustrates an example of a droplet forming apparatus including a liquid amount detection unit. In the droplet forming apparatus 10 </ b> A shown in FIG. 17A, a plurality of electrodes 15 are provided as liquid amount detection means in the depth direction of the inner wall surface of the liquid chamber 11. By using a conductive liquid as the solution 300 and examining the conduction or resistance value between the plurality of electrodes 15, the liquid amount of the solution 300 can be detected.

  In the droplet forming apparatus 10B shown in FIG. 17B, a light emitting element 16 and a position sensor 17 are provided above the liquid chamber 11 as liquid amount detection means. The position sensor 17 is disposed at a position where it can receive light emitted from the light emitting element 16 and regularly reflected by the liquid surface 300A and the liquid surface 300B of the solution 300. Thereby, based on the principle of triangulation, the distance from the position of the light received by the position sensor 17 to the liquid surface of the solution 300 can be calculated. However, the liquid amount detection means is not limited to that illustrated in FIG. 17, and various known distance measurement and liquid level detection techniques can be used.

  The drive device 30 can be configured so that the agitation waveform can be varied based on the output signal of the liquid amount detection means. For example, the drive device 30 selects an appropriate frequency with reference to a preset conversion formula or look-up table based on a signal related to the liquid amount detected by the liquid amount detecting means, and the stirring waveform shown in FIG. Can be configured to output.

  Alternatively, it can be combined with the stirring waveform for performing the frequency sweep shown in FIG. 13, and the values of the first frequency and the second frequency to be swept are determined based on the detection result of the liquid amount detection means. Can be configured.

  As described above, the droplet forming apparatuses 10A and 10B according to the third modification of the first embodiment include the liquid amount detecting unit that detects the liquid amount of the solution 300, and the driving device 30 is the liquid amount detecting unit. The stirring waveform is controlled based on the detection result. As a result, even if the natural frequency of the membrane 12 changes depending on the liquid volume, the liquid volume can be detected and a stirring waveform matched to the change of the natural frequency can be output. Can do.

<Modification 4 of the first embodiment>
In the fourth modification of the first embodiment, an example of a droplet forming apparatus that gives a stirring waveform with a predetermined time interval is shown. Note that in the fourth modification of the first embodiment, the description of the same components as those of the already described embodiments may be omitted.

  More preferably, the drive device 30 does not always input a stirring waveform while droplet formation is not being performed, but instead inputs a waveform with a predetermined time TB1 as shown in FIG. If the stirring waveform is always input, the power consumption increases, and the membrane 12 generates heat due to continuous vibration, which may have an adverse effect depending on the type of the solution 300 containing the sedimenting particles 350. In particular, when the solution 300 contains cells, heat generation is not preferable because the cells are damaged when the temperature is high. For this reason, it is preferable to minimize stirring.

  Furthermore, the stirring time interval TB1 is preferably set in accordance with the characteristics of the sedimentation particles 350 and the characteristics of the solvent in which the sedimentation particles 350 are dispersed. It is known that the sedimentation velocity of particles can be approximately expressed by the Stokes equation represented by the following equation (Equation 5).

ここで、ｖは粒子の沈降速度、ｇは重力加速度、ｒは粒子の半径、ηは溶媒の粘度、ρは粒子の密度、δは溶媒の密度を表している。例えば、半径５μｍ、密度１０５０ｋｇ／ｍ^３のポリスチレン微粒子が水中に分散しているとき、沈降速度ｖは約３μｍ／ｓとなる。粒子の濃度にもよるが、メンブレンの厚みは一般的に１０μｍ〜１００μｍの範囲であり、粒子が全体的に数μｍ程度沈降するとノズル詰まり等の影響が出始める。

Here, v is the sedimentation velocity of the particles, g is the acceleration of gravity, r is the radius of the particles, η is the viscosity of the solvent, ρ is the density of the particles, and δ is the density of the solvent. For example, when polystyrene fine particles having a radius of 5 μm and a density of 1050 kg / m ³ are dispersed in water, the sedimentation velocity v is about 3 μm / s. Although depending on the concentration of particles, the thickness of the membrane is generally in the range of 10 μm to 100 μm, and the influence of nozzle clogging or the like starts to appear when the particles settle on the order of several μm.

  Therefore, it is preferable to set TB1 which is the interval of stirring time to about 1 second or less. If the sedimentation speed v is about 3 μm / s and TB1 is about 1 second or less, the overall sedimentation of the particles while not being stirred can be suppressed to about 3 μm or less, so that nozzle clogging or the like can be suppressed.

  For example, the droplet forming apparatus may be configured such that the user can directly set the stirring time interval TB1. Alternatively, the above-described calculation can be performed inside the droplet forming apparatus, and when the user inputs basic data (for example, data such as solvent type, density, and viscosity), the optimum time interval is automatically set. TB1 may be calculated so that the stirring operation can be performed.

  As described above, in the droplet forming device according to the fourth modification of the first embodiment, the driving device 30 imparts a stirring waveform to the membrane 12 at predetermined time intervals. Thus, when droplet formation is not performed, it is possible to execute stirring for preventing sedimentation of the sedimentable particles 350 with a small amount of energy. At this time, the predetermined time interval is preferably set based on the characteristics of the sedimentation particles 350 and the like.

<Example>
Next, an embodiment in which the droplet forming apparatus 10 is made as a prototype and the solution 300 containing the sedimenting particles 350 is discharged will be described. In the prototype droplet forming apparatus 10, a bend-type ring piezo element (manufactured by Noriac, CMBR03) is used as the piezoelectric element 13, and a SUS pinhole having a nozzle diameter of 50 μm as the membrane 12 (manufactured by Edmund Optics, # 39-879) Was used. The purpose of this experiment is to verify the stirring effect of the sedimentary particles 350 due to the vibration of the membrane 12, and the stirring effect of the prototype droplet forming device 10 was verified using the observation device 500 shown in FIG.

  The observation apparatus 500 is configured such that the inside of the liquid chamber 11 of the droplet forming apparatus 10 can be observed by a CCD 502 with a lens 501 disposed above the droplet forming apparatus 10. Further, the droplet 310 containing the sedimentary particles 350 is ejected onto the preparation 504 installed on the automatic driving stage 505, so that the droplet 310 can be ejected in an arbitrary pattern shape. Yes.

  Stirring and discharging were performed by inputting a stirring waveform and a discharging waveform from the driving device 30 to the piezoelectric element 13. At that time, the dispersion state of the solution 300 containing the settling particles 350 filled in the liquid chamber 11 was observed with the CCD 502. Moreover, the number of the sedimentary particles 350 in the droplet 310 was measured by discharging the droplet 310 so as to be arranged linearly on the preparation 504. As the solution 300 containing the sedimenting particles 350, about 30 μl of a solution containing polystyrene particles having a diameter of about 10 μm (Thermo Scientific, Duke 2010A) was filled in the liquid chamber 11.

  Table 2 shows a sweep waveform including the natural frequency of the fundamental mode, a sweep waveform including the natural frequency of the higher-order mode, and the settling property inside the liquid chamber 11 when stirring is performed with three different stirring waveforms without signal input. It is an observation result of the stirring state of the particles 350. Here, the sweep waveform including the natural frequency of the fundamental mode is a waveform that sweeps a frequency range of about 18 kHz to 21 kHz over about 0.01 s. The sweep waveform including the natural frequency of the higher-order mode is a waveform that sweeps the frequency range of about 69 kHz to 71 kHz over about 0.01 s.

表２より、基本モードの固有振動数を含むスイープ波形では、全体的に均一な撹拌状態が観察できる。しかし、撹拌信号なしでは、粒子は沈降し、高次モードの固有振動数を含むスイープ波形ではメンブレン１２の面内に振動強度の分布が生じ、図２０（ａ）に模式的に示す粒子の偏りが観察された。なお、図２０（ａ）において、１１ａは液室１１の内壁面を示している。

From Table 2, a uniform stirring state can be observed as a whole in the sweep waveform including the natural frequency of the fundamental mode. However, without the stirring signal, the particles settle, and in the sweep waveform including the natural frequency of the higher-order mode, the distribution of the vibration intensity is generated in the plane of the membrane 12, and the particle bias schematically shown in FIG. Was observed. In FIG. 20A, 11a indicates the inner wall surface of the liquid chamber 11.

  The fundamental mode frequency range is about 18 kHz to 21 kHz, while the higher order mode frequency range is about 69 kHz to 71 kHz, and the higher order mode frequency range is about 3.5 times the fundamental mode frequency range. . This corresponds to the natural frequency f21 in Table 1 in which the magnification for the natural frequency of the fundamental mode is 3.43.

  According to Bernoulli's theorem, since the pressure is lower than the surroundings at a place where the flow velocity is high, the particles tend to be attracted to the vibration belly where the vibration speed is high, that is, the vibration intensity is large. At the natural frequency f21, the particles are attracted from the position of the node shown in FIG. 8 to the vicinity of the center of the region C divided by the node B as shown in FIG. It is thought that the unevenness of the particles shown occurred. As described above, it was confirmed that the use of the stirring signal in the frequency region of the natural frequency of the higher-order mode results in a non-uniform dispersion state.

  Next, the agitation waveform 31 </ b> C and the ejection waveform 32 </ b> C shown in FIG. 21 were alternately input, and the droplet 310 containing the sedimentary particles 350 was ejected on the preparation 504. Then, in order to verify the effect of suppressing variation in the number of sedimentation particles 350 in the ejected droplets 310 by stirring, the number of sedimentation particles 350 in the ejected droplets 310 was measured.

  At that time, the ejection was performed at 2 kHz, and the ejection waveform 32C was a simple trapezoidal wave with a voltage of 50v. Further, the stirring waveform 31C was a sweep waveform including the natural frequency of the fundamental mode, with the voltage Vs being 1.4 v and the stirring time Ts being 0.3 s. Then, after filling the liquid chamber 11 with the polystyrene particle solution as the solution 300 containing the settleable particles 350, the discharge was started immediately.

  Table 3 shows each of the first half of discharge elapsed time 0, 1 and 2 minutes (30 times each, measured 90 times in total) and the second half of discharge elapsed time 4 and 8 minutes (30 times each, measured 60 times in total). This is a result of measuring the number of sedimentation particles 350 in the ejected droplet 310 in a time zone and obtaining a standard deviation.

表３より、撹拌波形３１Ｃとして基本モードの固有振動数を含むスイープ波形を用いて撹拌を行った場合は、前半と後半ともに標準偏差に大きな変化はないが、撹拌信号なしの場合では前半に比べて後半に標準偏差が増大している。これは、吐出開始直後は沈降性粒子３５０の分散状態が保たれているため、液滴３１０中の沈降性粒子３５０の数のばらつきが生じ難いが、撹拌を行わない場合、時間の経過とともに沈降性粒子３５０の沈降が進み、分散状態の不均一が生じたためと考えられる。

From Table 3, when stirring is performed using a sweep waveform including the natural frequency of the fundamental mode as the stirring waveform 31C, there is no significant change in the standard deviation in both the first half and the second half, but in the case of no stirring signal compared to the first half In the second half, the standard deviation has increased. This is because the dispersion state of the sedimentation particles 350 is maintained immediately after the start of discharge, so that the number of sedimentation particles 350 in the droplets 310 is less likely to vary. This is presumably because the sedimentation of the conductive particles 350 progressed and the dispersion state became uneven.

  Thus, when stirring was performed, it was confirmed that the standard deviation of the number of the settling particles 350 in the droplets 310 hardly changed over time. That is, it was confirmed that the variation in the number of the sedimentary particles 350 in the ejected droplets 310 is suppressed by stirring using the vibration of the membrane 12.

  The preferred embodiments and the like have been described in detail above, but the present invention is not limited to the above-described embodiments and the like, and various modifications can be made to the above-described embodiments and the like without departing from the scope described in the claims. Variations and substitutions can be added.

DESCRIPTION OF SYMBOLS 10, 10A, 10B Droplet formation apparatus 11 Liquid chamber 11a Inner wall surface of liquid chamber 12 Membrane 13 Piezoelectric element 15 Electrode 16 Light emitting element 17 Position sensor 30 Drive device 31, 31C Stirring waveform 31A First stirring waveform 31B Second stirring Waveform 32, 32C Discharge waveform 111 Atmospheric open part 121 Nozzle 300 Solution 300A, 300B Liquid surface 310 Droplet 350 Precipitating particles

Japanese Patent Laid-Open No. 06-087220

Claims (7)

A liquid holding unit for holding a solution containing the settling particles;
A film-like member in which a nozzle is formed and discharges the solution held in the liquid holding portion as a droplet from the nozzle by vibration;
Vibration means for vibrating the membrane member;
Driving means for selectively applying to the vibration means a discharge waveform for vibrating the film-like member to form the droplet and a stirring waveform for vibrating the film-like member within a range where the droplet is not formed. And a droplet forming apparatus.   The droplet forming apparatus according to claim 1, wherein the stirring waveform includes a signal in a lower frequency region than a natural frequency of a higher-order mode of the film member.   The droplet forming apparatus according to claim 1, wherein the stirring waveform includes a natural frequency of a fundamental mode of the film member. The stirring waveform is a signal in which the frequency is changed from the first frequency to a second frequency different from the first frequency,
4. The droplet forming apparatus according to claim 3, wherein the natural frequency of the fundamental mode exists between the first frequency and the second frequency. Having a liquid amount detecting means for detecting the liquid amount of the solution;
5. The droplet forming apparatus according to claim 1, wherein the driving unit controls the stirring waveform based on a detection result of the liquid amount detection unit.   The droplet forming apparatus according to claim 1, wherein the driving unit applies the stirring waveform to the vibration unit at a predetermined time interval.   The droplet forming apparatus according to claim 6, wherein the predetermined time interval is set based on characteristics of the sedimentation particles.

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