JP2007108140A - Liquid transfer apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a liquid transfer apparatus capable of smoothly transferring liquids to channels and easily controlling the quantity of a transfer of the liquids while preventing chip breakage. <P>SOLUTION: In the liquid transfer apparatus 100, wells W1-W4 are formed on the surface side of a chip 10, and the chip 10 has a channel inside to be connected to the wells W1-W4. The wells W1-W4 are pressurized while the chip 10 comes in tight contact with a substrate 21 to transfer liquids in the wells W1-W4 to the channel. The substrate 21 has through holes 25b-25e for circulating gases to be supplied for the wells W1-W4 and a through hole 25a and is provided with both a gas supply means 23 for supplying gases for the through holes 25b-25e and pressurizing the wells W1-W4 and a pressure reduction means 24 for drawing the chip 10 to the substrate 21 by suction by reducing the pressure of the second through hole 25a. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a liquid transfer device, and more specifically, a liquid transfer device that transfers liquid from a well to a channel with respect to a chip having a well formed on the surface side and having a channel connected to the well inside. It is about.

  In the field of biotechnology and the like, a microchannel chip is used for detecting microorganisms and the like. A microchannel chip generally has a plurality of wells that store liquid and a flow path that connects the plurality of wells. Particularly recently, a microchannel chip having a plurality of wells for storing liquid on the surface side and connecting the wells with a flow path has been used. In such a microchannel chip, since the cross-sectional area of the flow path is extremely small, the liquid cannot be transferred to the flow path only by storing the liquid in the well. For this reason, in order to transfer the liquid from the well to the flow path, it is necessary to pressurize the liquid after the liquid is accommodated in the well.

Conventionally, for example, a method disclosed in Patent Document 1 below is known as a method of pressurizing a liquid and transferring it to a flow path in a chip. The method described in this document pressurizes the liquid while pressing the rigid member against the chip, and transfers the liquid to the flow path in the chip through the through hole of the rigid member.
Japanese Patent Laid-Open No. 2003-121311

  However, the rigid member has the following problems.

  That is, although the chip can be fixed by pressing the rigid member against the chip, the chip is sandwiched between the rigid member and the mounting table, so that the chip may be cracked or the chip may be damaged. Further, the channel is narrowed by the chip being sandwiched between the rigid member and the mounting table on which the chip is mounted. As a result, the following problems have occurred. That is, for example, when the rigid member is pressed against only a part of the chip, the chip is bent, a gap is generated between the chip and the rigid member, and the liquid leaks, so that the liquid cannot be sufficiently pressurized, The problem that the liquid cannot be transferred at a desired flow rate, and the problem that the pressure when the chip is sandwiched between the rigid member and the mounting table varies depending on the position on the flow path, or the pressure fluctuates every time the liquid is transferred. It was difficult to control the amount of liquid transferred. Furthermore, for the same reason, since the cross-sectional area of the flow path is narrowed, there is a problem that the liquid cannot be smoothly transferred to the flow path.

  The present invention has been made in view of the above circumstances, and provides a liquid transfer apparatus capable of smoothly transferring a liquid to a flow path and easily controlling the amount of liquid transferred while preventing breakage of a chip. Objective.

  In order to solve the above-mentioned problems, the present invention provides a liquid that is pressurized in a well while the chip is formed on the surface side and has a flow path connected to the well, and the chip is in close contact with the substrate, and is contained in the well. A liquid transfer apparatus for transferring a gas to a flow path, wherein the base has a first through hole and a second through hole through which a gas to be supplied to the well is circulated. And a gas supply means for pressurizing and a pressure reducing means for depressurizing the second through-hole and adsorbing the chip to the substrate.

  When using this liquid transfer apparatus, first, a chip having a well formed on the surface side and having a flow path connected to the well is prepared. Specifically, a chip having the same number of wells as the number of first through holes in the substrate and having the position of the well and the position of the first through hole coincide when the substrate and the chip are brought into close contact with each other is prepared. To do. For example, the liquid to be transferred is accommodated in any one of the plurality of wells of the chip. Next, this chip and the base are brought into contact so that the position of the well and the position of the first through hole coincide. In this state, when the second through hole is decompressed by the decompression means, the chip is adsorbed to the base. Next, gas is supplied to the first through hole by the gas supply means. Then, the liquid is pressurized by the gas, and this liquid is transferred to the flow path. At this time, since the chip is adsorbed to the base and there is no object sandwiching the chip together with the base, breakage of the chip is sufficiently prevented. Moreover, since the situation where the flow path is narrowed is surely prevented, the chip is sufficiently prevented from bending, the adhesion between the chip and the base is increased, and the gas leakage is sufficiently prevented. . As a result, the liquid can be sufficiently pressurized by the gas, and the liquid can be transferred at a desired flow rate. In addition, since there is no object sandwiching the chip with the substrate, the pressure applied to the chip is extremely small. For this reason, the situation where the pressure applied to the flow path becomes equal regardless of the position on the flow path and the pressure fluctuates every time the liquid is transferred is prevented. That is, the liquid transfer amount can be easily controlled. Furthermore, since the cross-sectional area of the flow channel cannot be reduced, the liquid can be smoothly transferred to the flow channel.

  In the liquid transfer device, the base has a concave portion on the surface side of the base and around the first through hole, the second through hole communicates with the concave portion, and is larger than the area of the opening on the concave side of the second through hole. Of the openings in the recesses, the area of the opening on the surface side of the substrate is preferably large.

  When the chip is disposed so as to cover the recess, the recess is decompressed when the second through hole is decompressed by the decompression means. Thereby, the chip is adsorbed by the substrate. At this time, since the opening area of the recess is larger than the area of the opening on the recess side of the second through hole, it is possible to further increase the suction force of the chip to the base. Accordingly, it is possible to sufficiently prevent the chip from being detached from the substrate during the liquid transfer.

It is preferable that the base body further includes a protruding portion that protrudes from the annular region around the annular region surrounding the recess, and a chip positioning portion that positions the chip is formed by the annular region and the protruding portion.

  In this case, if the chip is accommodated in the chip positioning portion, the chip can be easily positioned, and thus the time required to transfer the liquid can be greatly reduced.

  In the liquid transfer device, a chip container in which a chip positioning part for positioning a chip is formed on one side, and the chip container and the base are connected so that the surface of the base and the surface of the chip are in close contact with each other. It is preferable to further include connecting means capable of performing the above.

  In this case, if the chip is accommodated in the chip positioning portion, the chip can be easily positioned, and thus the time required to transfer the liquid can be greatly reduced.

  In the liquid transfer device, it is preferable that at least a part of the surface side of the substrate is an elastic body, and the first through hole and the second through hole penetrate the elastic body.

  In this case, since the adhesiveness between the elastic body and the chip is improved, the sealing performance is improved. That is, when gas is supplied to the well through the first through hole by the gas supply means, gas leakage is sufficiently prevented, so that the liquid can be efficiently transferred to the flow path.

  According to the liquid transfer device of the present invention, the liquid can be smoothly transferred to the flow path and the liquid transfer amount can be easily controlled while preventing breakage of the chip.

  Hereinafter, embodiments of the liquid transfer device of the present invention will be described in detail with reference to the drawings.

(First embodiment)
First, before describing the liquid transfer device, the configuration of a chip to which the liquid transfer device is applied will be described. FIG. 1 is a perspective view showing a chip to which the liquid transfer device according to the present embodiment is applied.

  As shown in FIG. 1, the chip 10 has a plurality of wells W1, W2, W3, and W4 on the surface 10a side, and a flow path 11 that connects the wells W1 and W2, the wells W2 and W3, and the wells W3 and W4. , 12 and 13 inside. Here, each of the wells W1 to W4 is opened to the atmosphere by one opening. Hereinafter, the surface 10a is referred to as "well formation surface 10a"). The wells W1 to W4 may be covered with a member having a plurality of openings, such as a filter member.

  In the present embodiment, for example, the well W1 is a sample well that contains a sample solution, the well W2 is an extraction well that contains a lyophilized product of the extraction reagent, and the well W3 is an amplification well that contains a lyophilized product of the amplification reagent, The well W4 is a luminescent well that houses a lyophilized product of the luminescent reagent.

  Next, the liquid transfer apparatus 100 that transfers liquid to the flow paths 11 to 13 in the chip 10 will be described. 2 is a perspective view showing an appearance of the liquid transfer device 100 according to the present embodiment, FIG. 3 is a schematic view showing the entire liquid transfer device 100, and FIG. 4 is a plan sectional view of the liquid transfer device 100 of the present embodiment. FIG. 5 and FIG. 5 are cross-sectional views along the line VV in FIG.

  As shown in FIGS. 2 and 4, the liquid transfer device 100 includes a flat substrate 21. The base 21 is made of, for example, a resin such as acrylic resin or polycarbonate, or a metal material such as aluminum or SUS. Moreover, it is preferable that the base | substrate 21 is a thing with few deformation | transformation. Five gas flow pipes 22 a to 22 e are connected to the one surface 21 a side of the base 21. As shown in FIG. 3, the gas flow pipe 22a connected to the center of the one surface 21a among the five gas flow pipes 22a to 22e is connected to the decompression device 24, and the gas flow pipes 22b to 22e provided around the gas flow pipes 22b to 22e. It is connected to the pressure device 23.

  Here, the pressurizing device 23 supplies a gas that does not react with the sample liquid, for example, an inert gas such as nitrogen gas, and is constituted by, for example, a gas cylinder filled with nitrogen gas or a syringe. The pressurizing device 23 may supply a gas that reacts with the sample liquid, for example, air. In that case, as the pressurizing device 23, for example, a compressor can be used. For example, a vacuum pump is used as the decompression device 24.

  Further, valves (not shown) are installed in the gas flow pipes 22b to 22e. In this case, by adjusting the opening and closing of the valves installed in the gas flow pipes 22b to 22e, the gas flow pipe for supplying the gas can be selected as appropriate, and thus the well to be pressurized can also be selected.

  The valve, the gas circulation pipes 22b to 22e, and the pressurizing device 23 constitute a gas supply means, and the gas circulation pipe 22a and the decompression device constitute a decompression means.

As shown in FIG. 5, the base 21 has first through holes 25b to 25e connected to the gas flow pipes 22b to 22d, respectively, and a second through hole 25a connected to the gas flow pipe 22a. . One common recess 26 is formed around the four first through holes 25b to 25e. Here, since the first through holes 25b to 25e are provided around the second through hole 25a, the area of the opening 26a on the surface 21a side of the base 21 in the opening of the recess 26 is the second through hole 25a. This is larger than the area of the opening on the recess 26 side. The second through hole 25 a communicates with the recess 26. Therefore, when the second through hole 25a is decompressed by the decompression device 24, the recess 26 is decompressed.
In addition, it is preferable that the distances between the first through holes 25b to 25e and the second through holes 25a are all equal. When the well is pressurized through the plurality of first through holes while reducing the pressure of the second through holes 25a to adsorb the substrate 21, all the distances between the first through holes 25b to 25e and the second through holes 25a are all Compared to the case where they are not equal, the possibility that the chip 10 is detached from the base 21 during the liquid transfer operation can be sufficiently reduced.

  Note that the opening of the recess 26 is smaller than the well forming surface 10 a of the chip 10, and the recess 26 can be covered by the chip 10.

  Next, a liquid transfer method using the liquid transfer apparatus 100 will be described.

  First, the chip 10 is prepared. Here, the number of wells in the chip 10 is four, and the number of first through holes in the base 21 is also four. The positions of the wells W1 to W4 correspond to the positions of the first through holes 25b to 25e in the base body 21. That is, when the base 21 and the chip 10 are brought into close contact with each other, the positions of the wells W1 to W4 coincide with the positions of the first through holes 25b to 25e. For example, the sample liquid to be transferred is accommodated in the well W1 which is the sample well among the plurality of wells W1 to W4 of the chip 10.

  Next, the chip 10 and the base body 21 are brought into contact so that the positions of the wells W1 to W4 and the positions of the first through holes 25b to 25e coincide. At this time, the well forming surface 10 a of the chip 10 is brought into contact so as to cover the concave portion 26 of the base 21. Thereby, the recess 26 is sealed by the chip 10. In this state, when the second through hole 25 a is decompressed by the decompression device 24, the sealed space formed by the recess 26 and the chip 10 is decompressed, and the chip 10 is adsorbed to the base 21. Next, gas is supplied to the first through holes 25b to 25e from the pressurizing device 23 through the gas flow pipes 22b to 22e.

  Then, the sample liquid is pressurized by the gas, and this liquid is transferred from the well W1 to the flow path 11. At this time, since the chip 10 is adsorbed to the base 21 and there is no object sandwiching the chip 10 together with the base 21, damage to the chip 10 is sufficiently prevented. In addition, since there is no object sandwiching the chip 10 together with the base 21, the situation where the flow path 11 is narrowed is surely prevented, so that the chip 10 is sufficiently prevented from being bent. The adhesion between the two increases, and gas leakage is sufficiently prevented. As a result, the liquid can be sufficiently pressurized by the gas, and the liquid can be transferred at a desired flow rate. Further, since there is no object sandwiching the chip 10 together with the base body 21, the pressure applied to the chip 10 becomes extremely small. For this reason, the pressure applied to the flow path 11 becomes equal regardless of the position on the flow path 11, and the situation where the pressure changes every time the liquid is transferred is also prevented. Therefore, the amount of liquid transferred can be easily controlled. Furthermore, since the cross-sectional area of the flow path 11 is prevented from being narrowed, the liquid can be smoothly transferred to the flow path 11.

  Furthermore, in this embodiment, one common recessed part 26 is formed around the plurality of first through holes 25b to 25e. Moreover, since the area of the opening on the surface 21a side of the base 21 in the opening of the recess 26 is larger than the area of the opening on the recess 26 side of the second through hole 25a, compared with the case where the recess 26 is not formed. Thus, it is possible to further increase the suction force of the chip 10 to the base 21. Therefore, the situation where the chip 10 is detached from the base 21 during the transfer of the sample liquid to the flow path 11 is sufficiently prevented.

  When the sample liquid is transferred to the flow path 11 in this way, the sample liquid is transferred to the well W2 and dissolves the extraction reagent that is a lyophilized body. In this way, an extraction reagent mixed liquid of the extraction reagent and the sample liquid is obtained. When this extraction reagent mixed liquid is transferred to the flow path 12, the gas is supplied to the gas flow pipes 22 b and 22 c by the pressurizing device 23. Here, the reason why the gas is supplied also to the gas flow pipe 22b is to prevent the extraction reagent mixture from flowing backward to the flow path 11 side by pressurizing the well W1. At this time, the gas flow pipe 22 a is kept in a reduced pressure state by the pressure reducing device 24. Thereby, the extraction reagent mixed solution accommodated in the well W2 is transferred to the flow path 12 by the gas flowing through the gas flow pipe 22c. Then, this extraction reagent mixed solution is transferred to the well W3 through the flow path 122, and dissolves the amplification reagent which is a lyophilized body accommodated in the well W3. Thus, an amplification reagent mixed solution is obtained.

  When the amplification reagent mixture is transferred to the flow path 13, the amplification reagent mixture contained in the well W3 may be pressurized as described above. In this way, the amplification reagent mixed solution dissolves the luminescent reagent which is a lyophilized product, and light emission is observed.

(Second Embodiment)
Next, a second embodiment of the liquid transfer device of the present invention will be described. In addition, the same code | symbol is attached | subjected about the component same or equivalent to 1st Embodiment, and the overlapping description is abbreviate | omitted.

  FIG. 6 is a side view showing a second embodiment of the liquid transfer apparatus of the present invention. As shown in FIG. 6, the liquid transfer apparatus 200 of the present embodiment further includes a chip container 32 in which a chip positioning part 31 for positioning the chip 10 is formed on the one surface 31 a side. It differs from the liquid transfer device 100 of the first embodiment in that the base 21 is connected by a hinge 33.

  Here, the base 21 can be opened / closed relative to the chip 10 with the hinge 33 as the center, and the chip positioning portion 31 is closed when the base 21 is closed with respect to the chip housing 32. The wells W1 to W4 in the chip 10 and the first through holes 25b to 25e in the base body 21 are formed at the same positions. The chip positioning unit 31 is formed so as not to rotate the chip 10 in the chip positioning unit 31 when the chip 10 is accommodated in the chip positioning unit 31.

  For this reason, according to the liquid transfer apparatus 200, when the chip 10 is accommodated in the chip positioning unit 31, the chip 10 is positioned so as not to rotate with respect to the chip container 32. Moreover, when the chip 10 is accommodated in the chip positioning portion 31, the position of the first through holes 25 b to 25 e in the base 21 and the position in the chip 10 when the base 21 is closed with respect to the chip containing body 32 around the hinge 33. The positions of the wells W1 to W4 can be matched, and the surface 21a of the base 21 and the surface 10a of the chip 10 can be brought into close contact with each other. For this reason, when the chip 10 is accommodated in the chip positioning part 31, the chip 10 can be easily positioned, and thus the time required for transferring the sample liquid can be greatly shortened.

  In the present embodiment, the connecting means is constituted by the hinge 33, but the connecting means is not limited to the hinge 33. For example, among the plurality of recesses provided on the surface of the base body 21 where the openings of the first through holes 25b to 25e are formed and the surface of the chip container 32 on which the chip positioning portion 31 is formed, You may be comprised with the some convex part provided in an outer surface. Here, it is preferable that the convex portion can be fitted into the concave portion in order to improve the positioning accuracy of the chip 10. In addition, when the shape of the opening of a recessed part is a polygon (for example, square, a triangle, etc.), you may have one recessed part and one convex part, respectively. Furthermore, the base body 21 may have a convex portion, and the chip container 32 may have a concave portion.

(Third embodiment)
Next, a third embodiment of the liquid transfer device of the present invention will be described with reference to FIG. In addition, the same code | symbol is attached | subjected about the component same or equivalent to 1st or 2nd embodiment, and the overlapping description is abbreviate | omitted.
FIG. 7 is a cross-sectional view showing a third embodiment of the liquid transfer apparatus of the present invention. As shown in FIG. 7, in the liquid transfer device 300 of the present embodiment, the base 10 has an annular region 27 around the recess 26, and an annular protrusion that protrudes from the annular region 27 around the annular region 27. It differs from the liquid transfer apparatus 100 of 1st Embodiment by the point which has 28 further.

  Here, a chip positioning portion 29 for positioning the chip 10 is formed by the annular region 27 and the protruding portion 28. The chip positioning unit 29 does not rotate the chip 10 even if the chip 10 is accommodated. In addition, the chip positioning unit 29 is configured to match the positions of the first through holes 25 b to 25 e in the base 21 with the positions of the wells W1 to W4 in the chip 10 when the chip 10 is accommodated.

  Therefore, when the chip positioning portion 29 is formed on the base body 21, the chip 10 can be easily positioned, and the time required for transferring the sample liquid can be greatly shortened.

  The present invention is not limited to the first to third embodiments. For example, in the first to third embodiments, in the base 10, one common concave portion 26 is formed around the four first through holes 25 b to 25 e, but the concave portion 26 may not be formed. Good. Moreover, when the base | substrate 21 has the some 2nd through-hole 25a, you may have the recessed part 26 according to the number of the 2nd through-holes 25a.

  Furthermore, in the liquid transfer devices 100, 200, and 300 according to the first to third embodiments, the portion of the base 21 on the surface 21a side that contacts the well forming surface 10a is an elastic body. It is preferable that the first through holes 22b to 22e and the second through hole 22a pass through an elastic body (not shown). In this case, since the adhesiveness between the elastic body and the chip 10 is improved, the sealing performance is improved. That is, when gas is supplied to the wells W1 to W4 through the gas flow pipes 22b to 22e and the first through holes 25b to 25e by the pressurizing device 23, gas leakage is more sufficiently prevented, so that the sample liquid is efficiently used. It can be well transferred to the channels 11-13. The elastic body as described above only needs to have a larger elastic modulus than the material constituting the base body 21, and for example, silicone rubber or the like can be used as the elastic body. Note that a part of the base 21 may be an elastic body, but the whole may be an elastic body.

  Further, the chip to which the liquid transfer device of the present invention is applied is not limited to the chip 10 of the first to third embodiments. Of course, it is possible to use a chip in which the number of wells is increased or decreased and a chip in which the position and size of the wells are changed as necessary. However, in this case, the position and size of the first through hole and the second through hole in the base are set to the position and size corresponding to the chip, that is, through the first through hole while reducing the pressure of the second through hole. It is necessary to set the position and size where the well can be pressurized.

It is a perspective view which shows an example of the chip | tip used with embodiment of the liquid transfer apparatus of this invention. It is a perspective view which shows the external appearance of one Embodiment of the liquid transfer apparatus of this invention. It is the schematic which shows the whole liquid transfer apparatus of FIG. FIG. 3 is a plan sectional view showing the liquid transfer device of FIG. 2. It is sectional drawing along the VV line of FIG. It is sectional drawing which shows other embodiment of the liquid transfer apparatus of this invention. It is sectional drawing which shows other embodiment of the liquid transfer apparatus of this invention.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 10 ... Chip, 10a ... Well formation surface (surface), 11-13 ... Flow path, 21 ... Base, 21a ... One side, 22a-22e ... Gas distribution pipe, 23 ... Pressurization device, 24 ... Decompression device, 25a ... No. 2 through-holes, 25b to 25e... 1st through-hole, 26... Recess, 26a... Opening on the surface side of the substrate among the openings in the recess, 27. Positioning portion, 31a ... one side, 32 ... chip container, 33 ... hinge, 100, 200, 300 ... liquid transfer device, W1-W4 ... well.

Claims (5)

A liquid in which a well is formed on the surface side and pressurizes the well while a chip having a flow path connected to the well is in close contact with the substrate, and the liquid contained in the well is transferred to the flow path A transfer device comprising:
The base has a first through hole for allowing a gas to be supplied to the well and a second through hole;
Gas supply means for supplying gas to the first through-hole and pressurizing the well;
Decompression means for depressurizing the second through hole and adsorbing the chip to the substrate;
A liquid transfer device comprising:   The base has a recess on the surface side of the base and around the first through hole, the second through hole communicates with the recess, and the area of the opening of the second through hole on the recess side 2. The liquid transfer apparatus according to claim 1, wherein an area of an opening on a surface side of the base body is large among openings of the recess.   The base further includes a protruding portion that protrudes from the annular region around an annular region that surrounds the recess, and a chip positioning portion that positions the chip is formed by the annular region and the protruding portion. The liquid transfer device according to claim 2. A chip container in which a chip positioning part for positioning the chip is formed on one surface side;
Connection means capable of connecting the chip container and the base body so that the surface of the base body and the surface of the chip are in close contact with each other;
The liquid transfer device according to claim 1, further comprising:   The at least part of the surface side of the said base | substrate is an elastic body, The said 1st through-hole and the said 2nd through-hole have penetrated the said elastic body, The any one of Claims 1-4 characterized by the above-mentioned. The liquid transfer device according to one item.

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