Microchip solution sending system
09952210 ยท 2018-04-24
Assignee
Inventors
Cpc classification
B01L2400/0487
PERFORMING OPERATIONS; TRANSPORTING
B01L3/502715
PERFORMING OPERATIONS; TRANSPORTING
International classification
Abstract
A microchip solution sending system may include a flow passage assembly that is at least provided with a fine flow passage that is provided with a detection region including a formed reaction field to which an antibody that reacts with a specific antigen is fixed; and a micro pump that is connected to the flow passage assembly and that is configured to send a specimen material solution that includes the specific antigen in a reciprocating manner. The specimen material solution that has been sent may pass through the detection region in a repetitive manner in the case in which the micro pump sends the specimen material solution in a reciprocating manner.
Claims
1. A microchip solution sending system for use with a specimen material solution, the system comprising: a flow passage assembly comprising a fine flow passage comprising a detection region comprising a formed reaction field to which an antibody that reacts with a specific antigen is fixed; and a micro pump that is connected to the flow passage assembly and that is structured to send the specimen material solution that includes the specific antigen in a reciprocating manner, wherein the specimen material solution that has been sent passes through the detection region in a repetitive manner in the case in which the micro pump sends the specimen material solution in a reciprocating manner, the microchip solution sending system comprises a controller structured to measure the amount of a solution that is sent from the micro pump, and reverse the solution sending direction of the micro pump, the fine flow passage further comprises: a first inflow outflow hole that is formed at the edge part of one side of the fine flow passage; a second inflow outflow hole that is formed at the edge part of the other side of the fine flow passage; a one side flow passage part where the reaction field is not formed, the one side flow passage part connecting the first inflow outflow hole and the detection region; and an other side flow passage part where the reaction field is not formed, the other side flow passage part connecting the detection region and the second inflow outflow hole; wherein the one side flow passage part, the detection region, and the other side flow passage part are coaxial; and wherein a cross-sectional area of the fine flow passage is approximately equivalent along its length; the flow passage assembly further comprises: a one side flow passage that is connected to the fine flow passage via the first inflow outflow hole in such a manner that a solution can be passed through; and an other side flow passage that is connected to the fine flow passage via the second inflow outflow hole in such a manner that a solution can be passed through, and the micro pump is connected to the one side flow passage, and the other side flow passage is a mixing part that is configured to store the specimen material solution that has passed through the detection region of the fine flow passage on a temporary basis and to stir the specimen material solution that has been stored, and wherein the controller is structured to measure the amount of a solution that is sent from the micro pump, and control the micro pump to reverse the solution sending direction of the specimen material solution when the measured amount of the sent solution reaches a predetermined amount of the sent solution, such that the specimen material solution is reciprocated between the detection region and the mixing part; wherein the controller is structured to control the micro pump such that approximately all of the specimen material solution passes the detection region before the solution sending direction is reversed; and wherein at least one of the first inflow outflow hole and the second inflow outflow hole has a central axis nonparallel to a central axis of the fine flow passage.
2. The microchip solution sending system as defined in claim 1, wherein the microchip solution sending system is used for a surface plasmon resonance apparatus (an SPR apparatus) or a surface plasmon-field enhanced fluorescence spectroscopic measurement apparatus (an SPFS apparatus).
Description
BRIEF DESCRIPTION OF THE DRAWINGS
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DESCRIPTION OF EMBODIMENTS
(15) An embodiment of the present invention will be described below in detail with reference to the drawings.
First Embodiment
(16)
(17) As shown in
(18) As described later, in the case in which the flow passage assembly A is filled with a specimen material solution 36 and the specimen material solution 16 that has been filled with is sent in a reciprocating manner inside the flow passage assembly A by the micro pump 40, the specimen material solution 36 that has been sent can pass through the detection region 20 in a repetitive manner.
(19) As shown in
(20) Although a shape of a cross sectional surface and the dimensions of the fine flow passage 10 are not restricted in particular, the fine flow passage 10 is formed in a generally rectangular shape of a cross section in which a flow passage width is in the range of 0.5 mm to 3 mm and a flow passage height is in the range of 50 m to 500 m for instance. In addition, although a length of the flow passage of the fine flow passage 10 is not restricted in particular, the flow passage length is in the range of 2 mm to 30 mm, and in the range of 2 mm to 20 mm preferably for instance.
(21) A detection region 20 is provided with a reaction field 22 that has been formed by fixing an antibody that reacts with a specific antigen in an idiosyncratic way to the bottom surface of the flow passage. In the case in which the specimen material solution 36 passes through the detection region 20, a specific antigen (analyte) that is included in the specimen material solution 36 reacts with an antibody that is fixed to the reaction field 22 in an idiosyncratic way and the specific antigen is captured by an antibody that is fixed to the reaction field 22.
(22) A forming range of the reaction field 22 is appropriately configured in consideration of a shape of the fine flow passage 10 and an amount of an analyte that is supplied in such a manner that an analyte of a desired amount can be captured in an efficient manner, and the forming range of the reaction field 22 is not restricted in particular. In the present embodiment for instance, the reaction field 22 is formed along the whole width of the bottom surface of the fine flow passage 10, and a length in the direction of the flow passage is in the range of 1 mm to 3 mm.
(23) As shown in
(24) Although a shape of a cross sectional surface and the dimensions of the first inflow outflow hole 12 and the second inflow outflow hole 14 are not also restricted in particular, the first inflow outflow hole 12 and the second inflow outflow hole 14 are formed in a circular shape that is provided with a diameter that is almost equivalent to the flow passage width in the range of 0.5 mm to 3 mm of the fine flow passage 10 described above for instance.
(25) As shown in
(26) The one side flow passage 32 is configured in such a manner that the specimen material solution 36 that is sent in a reciprocating manner can be flown through the one side flow passage 32, and the shape or the like is not restricted in particular. Moreover, the one side flow passage 32 can also be formed in an integrated manner with the fine flow passage 10, or can be connected to an object that has been formed individually from the fine flow passage 10. The one side flow passage 32 in accordance with the present embodiment is a pipette 32 that has been formed individually from the fine flow passage 10, and is configured in a detachable manner from the fine flow passage 10.
(27) As shown in
(28) The shape or the like of the other side flow passage 34 is not also restricted in particular. It is preferable that the other side flow passage 34 is formed as a mixing part 34 that is provided with a shape of a cross sectional surface that is larger than that of the second inflow outflow hole 14 described above. By this configuration, the specimen material solution 36 that has flown into the other side flow passage 34 (the mixing part 34) is stirred. Consequently, the specimen material solution 36 can be sent in a reciprocating manner in a repetitive manner without reducing the reaction efficiency for the detection region 20.
(29) This is because the specimen material solution 36 is flown in the fine flow passage 10 in a laminar flow state, that is, a state in which the streamlines of fluids are generally parallel to each other on a constant basis. Consequently, in the case in which the mixing part 34 is not formed, the specimen material solution 36 of the same layer comes into contact with the reaction field 22 on a constant basis. As a result, only a part of the specimen material solution 36 contributes to a reaction. On the other hand, the mixing part 34 is formed in such a manner that a cross sectional shape of the mixing part 34 is larger than a cross sectional surface of the second inflow outflow hole 14. Consequently, in the case in which the specimen material solution 36 is flown into the mixing part 34, the specimen material solution 36 that is stored inside the mixing part 34 on a temporary basis is stirred due to a turbulence of a flow of the specimen material solution 36 that has been flown in a laminar flow state. Accordingly, even in the case in which the specimen material solution 36 passes on the detection region 20 in a repetitive manner, only the same layer does not come into contact with the reaction field 22, and most of the specimen material solution 36 contributes to a reaction on the reaction field 22.
(30) A micro pump 40 is connected to an edge part on an opposite side of the fine flow passage 10 of the one side flow passage 32 described above. The micro pump 40 is a syringe pump that is configured to discharge and suck an air (or liquid) for the one side flow passage 32 for instance. In the case in which an air (or liquid) is discharged from the micro pump 40 to the pipette 32, the specimen material solution 36 can be sent from one side to the other side inside the flow passage assembly A as described above. Moreover, in the case in which an air (or liquid) of the pipette 32 is sucked by the micro pump 40, the specimen material solution 36 can be sent from the other side to one side inside the flow passage assembly A.
(31) As shown in
(32) For the microchip solution sending system 1 in accordance with the present invention, an embodiment of the micro pump 40 is not restricted to the above described embodiment. For instance, even in the case in which two micro pumps: a micro pump capable of performing only a discharge and a micro pump capable of performing only a suction are prepared and the two micro pumps are connected to the both edge parts of the flow passage assembly A, respectively, the specimen material solution 36 can be sent in a reciprocating manner inside the flow passage assembly A.
(33) In the next place, the following describes a flow of a specimen material solution 36 for a microchip solution sending system 1 in accordance with the present invention that is configured as described above based on
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(35) In the state shown in
(36) In addition, a solution sending amount Qp (l) that is set in advance as a solution sending amount of the micro pump 40 is stored into the storage means 46 of the control part 48 described above. In this case, in the case in which a total solution amount of the specimen material solution 36 that has been held in the pipette 32 described above is Q (l) and a solution amount of the specimen material solution 36 that is corresponded to a volume of a space of the detection region 20 is Q1 (l), a solution sending amount Qp that is set in advance in accordance with the present embodiment is obtained by the following formula (1).
Qp=QQ1(1)
(37) In the next place, the micro pump 40 is operated from the initial state shown in
(38) In the case in which a volume Vd of an air that is discharged from the micro pump 40 to the pipette 32 reaches a solution sending amount Qp that has been set in advance, a command is issued from the solution sending direction control means 44 sending direction control means 44 to the micro pump 40, and the micro pump 40 is then operated to suck an air of the pipette 32 as that a solution sending amount Qp that has been set in advance has been sent.
(39) In this case, in the state shown in
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(41) In the next place, in the case in which the micro pump 40 is operated from the state shown in
(42) In the case in which a volume Vs of an air that is sucked from the pipette 32 by the micro pump 40 reaches a solution sending amount Qp that has been set in advance, a command is issued from the solution sending direction control means 44 described above to the micro pump 40, and the micro pump 40 is then operated to discharge an air to the pipette 32 as that a solution sending amount Qp that has been set in advance has been sent.
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(44) After that, by repeating the processes described above, the specimen material solution 36 is sent in a reciprocating manner inside the flow passage assembly A.
(45) As described above, the microchip solution sending system 1 in accordance with the present invention is provided with a solution sending amount measurement means 42 that is configured to measure the amount of a solution that is sent from the micro pump 40 and a solution sending direction control means 44 that is configured to reverse the solution sending direction of the micro pump 40. In the case in which a volume Vd of an air that is discharged from the micro pump 40 (a volume Vs of an air that is sucked by the micro pump 40) reaches a solution sending amount Qp that has been set in advance as a solution sending amount of the micro pump 40, the solution sending direction is reversed in an automated way. Consequently, in the case in which a state shown in
(46) Consequently, by the microchip solution sending system 1 in accordance with the present invention, the specimen material solution 36 can be sent in a reciprocating manner without the ingress of an air into a detection region 20 even in the case in which a solution amount of the specimen material solution 36 is small. Therefore, an active condition of an antibody that is fixed to the reaction field 22 can be prevented from being reduced, and a bubble of air can be prevented from being attached to an antibody, thereby preventing the reaction efficiency from being decreased.
(47) In particular, by the microchip solution sending system 1 in accordance with the present invention, the specimen material solution 36 can be sent in a reciprocating manner in such a manner that an air-liquid interface gl (gl) of the specimen material solution 36 is located on a fine interfacial boundary of the detection region 20. Consequently, a small amount of the specimen material solution 36 can be applied to a reaction to the maximum extent possible.
(48) In the case in which the microchip solution sending system 1 in accordance with the present invention is used for a surface plasmon resonance apparatus (an SPR apparatus) or a surface plasmon-field enhanced fluorescence spectroscopic measurement apparatus (an SPFS apparatus), an SPR apparatus or an SPFS apparatus that is provided with the high reaction efficiency and a high accuracy with a small dispersion between individual pieces can be implemented.
Second Embodiment
(49) A microchip solution sending system 1 in accordance with a second embodiment of the present invention will be described below in detail with reference to
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(51) For the first embodiment of the present invention described above, the description was made as that a volume Vd of an air that is discharged from the micro pump 40 (a volume Vs of an air that is sucked by the micro pump 40) is equivalent to a solution sending amount Qp of the specimen material solution 36 that has been set in advance. In other words, a compression rate of an air is not considered for the first embodiment of the present invention described above.
(52) However, a volume of an air is varied depending on a temperature and a pressure. Consequently, in order to control a timing of a reverse of a solution sending direction of the specimen material solution 36 in a more precise manner, it is necessary to consider a compression rate (an expansion rate) of an air.
(53) Therefore, the microchip solution sending system 1 in accordance with the present embodiment is provided with a temperature and pressure measurement means 50 that is configured to measure a temperature and a pressure inside the flow passage assembly A as shown in
(54) For the microchip solution sending system 1 in accordance with the present embodiment moreover, as shown in
(55) A volume Vd (Vs) of an air that has been measured by the solution sending amount measurement means 42 is then corrected by using a compression rate (an expansion rate) described above. In the case in which a volume Vd (Vs) of an air after the correction reaches a solution sending amount Qp that has been set in advance, the solution sending direction is reversed by the solution sending direction control means 44.
(56) For the microchip solution sending system 1 in accordance with the present embodiment that has been configured as described above, a more precise control of a solution sending amount can be easily carried out in consideration of a compression rate (an expansion rate) of an air.
(57) For the embodiment as described above moreover, in the initial state shown in
(58) As shown in
(59) In this case, in the case in which a total solution amount of the specimen material solution 36 is Q(l), a solution amount of the specimen material solution 36 that is corresponded to a volume of a space of the detection region 20 is Q1(l), and a solution amount of the specimen material solution 36 that is corresponded to a volume of a space for a region 28 of the fine flow passage that is corresponded to a distance L described above is Qr(l), a solution sending amount Qp that is set in advance as a solution sending amount of the micro pump 40 can be set as indicated by the following formula (2).
Qp=QQ1Qr(2)
(60) In the case in which an air-liquid interface gl on the other side of the specimen material solution 36 is located at a distance L from an interfacial boundary position between the detection region 20 and the other side flow passage part 26 in the initial state as described above, as shown in
Third Embodiment
(61) A microchip solution sending system 1 in accordance with a third embodiment of the present invention will be described below in detail with reference to
(62)
(63) For the present embodiment, as compared with the above described embodiment, the following points are different from the above described embodiment: the one side flow passage 32 is not connected to an edge part on one side of the fine flow passage 10, the fine flow passage 10 and the micro pump 40 are directly connected to each other, and a specimen material solution container 38 that is configured to contain the specimen material solution 36 is connected to the micro pump 40. The flow passage assembly A in this case is configured by the fine flow passage 10 and the mixing part 34.
(64) For the microchip solution sending system 1 in accordance with the third embodiment, the specimen material solution 36 is sent in a reciprocating manner as shown in
(65) That is to say, in the case in which the micro pump 40 is operated in the initial state shown in
(66) After the all of the specimen material solution 36 that has been contained in the specimen material solution container 38 is discharged to the fine flow passage 10, as shown in
(67) In the case in which the total sum of a solution amount Qd of the specimen material solution 36 that is discharged from the micro pump 40 to the fine flow passage 10 and a volume Vd of an air that is discharged reaches a solution sending amount Qp that has been set in advance (a state shown in
(68) In the states shown in
(69) In the case in which the micro pump 40 sucks an air of the one side flow passage part 24 of the fine flow passage 10, the specimen material solution 36 is sent from the other side to the one side of the flow passage assembly A as shown in
(70) In the case in which the total sum of a volume Vs of an air and a solution amount Qs of the specimen material solution 36 that have been measured by the solution sending amount measurement means 42 reaches a solution sending amount Qp that has been set in advance, an air-liquid interface gl on the one side of the specimen material solution 36 is located on an interfacial boundary between the detection region 20 and the other side flow passage part 26 and the initial state shown in
(71) For the microchip solution sending system 1 in accordance with the present invention as described above, it is also possible that the one side flow passage 32 is not connected to an edge part on one side of the fine flow passage 10 and the fine flow passage 10 and the micro pump 40 are directly connected to each other.
(72) For the microchip solution sending system 1 in accordance with the present invention moreover, in the case in which the specimen material solution 36 is sent in a reciprocating manner by the micro pump 40, the specimen material solution 36 can also be sent via a fluid such as an air. In addition, the specimen material solution 36 can also be sent in a reciprocating manner by directly discharging or sucking the specimen material solution 36.
(73) Moreover, in the case in which the specimen material solution 36 is sent in a reciprocating manner via a fluid by the micro pump 40, as long as the fluid does not cause a change of the property of the specimen material solution 36, the fluid can also be a gas other than an air described above or can also be a liquid.
(74) While the preferred embodiments in accordance with the present invention have been described above, the present invention is not restricted to the embodiments described above, and various changes, modifications, and functional additions can be thus made without departing from the scope of the present invention.
(75) In the first to third embodiments described above for instance, the mixing part 34 as a second flow passage is connected to the edge part on the other side of the fine flow passage 10. Moreover, the mixing part 34 and the fine flow passage 10 are connected to each other via the second inflow outflow hole 14 in such a manner that a solution can be flown through.
(76) However, the microchip solution sending system 1 in accordance with the present invention is not restricted to the embodiments described above. As shown in
REFERENCE SIGNS LIST
(77) 1: Microchip solution sending system 10: Fine flow passage 12: First inflow outflow hole 14: Second inflow outflow hole 20: Detection region 22: Reaction field 24: One side flow passage part 26: The other side flow passage part 28: Region 32: One side flow passage (pipette) 34: The other side flow passage (mixing part) 36: Specimen material solution 38: Specimen material solution container 40: Micro pump 42: Solution sending amount measurement means 44: Solution sending direction control means 46: Storage means 48: Control part 50: Temperature and pressure measurement means 100: Microchip solution sending system 110: Fine flow passage 112: First inflow outflow hole 114: Second inflow outflow hole 120: Detection region 122: Reaction field 132: One side flow passage 134: The other side flow passage 136: Specimen material solution 140: Micro pump 142: Solution level confirmation sensor 144: Solution level confirmation sensor A: Flow passage assembly gl and gl: Air-liquid interfaces