Microfluidic Chip Adapter
The PDMS-based micro-channel chip adaptor with an integral thin film in the connecting hole addresses the challenges of maintaining sterilization and preventing damage during sample injection, while simplifying manufacturing for microchannels of small dimensions.
Patent Information
- Application Number
- JP2021040447
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Filing Date
- 2021-03-12
- Publication Date
- 2025-06-06
- Estimated Expiration
- 2041-03-12
AI Technical Summary
Conventional micro-channel chip adapters face challenges in maintaining the microchannel in a sterilized state and preventing damage during sample injection, while also being complex to manufacture for microchannels with small widths and lengths.
A micro-channel chip adaptor made of PDMS with a cylindrical body and a connecting hole that includes a thin film integral to the inner wall, allowing for sterilization and sample injection without exposing the microchannel to the outside environment.
The adaptor effectively maintains the microchannel in a sterilized state until sample injection, prevents leakage and damage, and simplifies the manufacturing process for microchannels of various sizes.
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Abstract
Description
[Technical field]
[0001] The present invention relates to a micro-channel chip adaptor that is fitted closely to the periphery of an opening of a through-hole that communicates with a micro-channel on the surface of a micro-channel chip and is used for injecting a sample from a pipette into the micro-channel, and more specifically, to a micro-channel chip adaptor that can keep the micro-channel in a sterilized state until a sample is injected from the pipette into the micro-channel. [Background technology]
[0002] A microchannel chip is a device in which two laminated substrates are formed with minute microchannels with widths of approximately 500 nm to 1 mm, and through-holes that open the microchannels to the outside. Microscopic samples such as organic compounds and biological samples are injected into the microchannels through the through-holes, and the chips are used for mixing, reacting, synthesizing, extracting, analyzing, and other applications.
[0003] When attempting to inject a sample into a microchannel by directly inserting the tip of a pipette or tube into a through-hole, the tip of the pipette or tube may come into contact with the bottom of the microchannel, damaging the bottom of the microchannel or preventing the sample from being injected into the microchannel. Therefore, a known microchannel chip adapter 100 is shown in FIG. 9, which is made up of a cylindrical body 102 through which a connecting hole 101 supporting the tip of a tube 110 passes, and has its bottom surface in intimate contact with the surface of microchannel chip 120 around the opening of through-hole 122 at a position where connecting hole 101 communicates with through-hole 122 which communicates with microchannel 121 of microchannel chip 120 (Patent Document 1).
[0004] According to this micro-channel chip adapter 100, the tip of tube 110 can be positioned within connecting hole 101 penetrating cylindrical body 102 before the tip reaches micro-channel 121, so there is no risk of damaging micro-channel 120. Furthermore, the bottom surface of micro-channel chip adapter 100 is in close contact with the surface of micro-channel chip 120 around the opening of through-hole 122, so the sample is injected from the tube through connecting hole 101 and through-hole 122 into micro-channel 121 without leaking out from the gap between micro-channel chip adapter 100 and the surface of micro-channel chip 120.
[0005] On the other hand, when the microchannel of the microchannel chip is in communication with the outside through the through-hole, various microorganisms such as airborne germs, moisture, and oxygen are mixed in, and if a sample that is easily decomposed or invaded by these microorganisms, moisture, and oxygen is injected from a pipette or tube, the reaction is inhibited and accurate test results cannot be obtained. For this reason, in the past, sterilization treatments such as ultraviolet irradiation, radiation irradiation, electron beam irradiation, corona discharge irradiation, plasma irradiation, and steam pressure sterilization (autoclave) were performed on the microchannel chip just before injecting the sample from the pipette or tube. However, after performing these sterilization treatments, the microchannel is exposed to the outside air until the communication hole of the microchannel chip adapter is blocked with a pipette or tube, so the sterilized state cannot be maintained during that time, and it is also cumbersome to perform sterilization treatments just before each sample injection.
[0006] 9, when micro-channel chip 120 is formed by laminating upper substrate 123 and lower substrate 124, each having through-hole 122 formed therein, non-adhesive thin-film layer 125 is formed in the portion of lower substrate 124 where micro-channel 121 is to be formed, and upper substrate 123 and lower substrate 124 are bonded and integrated entirely facing each other, leaving non-adhesive thin-film layer 125, as shown in FIG 8. As a result, in the portion of micro-channel chip 120 where micro-channel 121 is to be formed, non-adhesive thin-film layer 125 on lower substrate 124 is in close contact with the lower surface of upper substrate 123, and the gap therebetween is sealed off from the outside.
[0007] When a sample is injected from the tip of tube 110 into microchannel 121, a positive pressure is applied from tube 110 inserted into communication hole 101 of microchannel chip adapter 100 to through-hole 122 of microchannel chip 120 immediately before or at the same time as the injection of the sample, and a space for microchannel 121 into which the sample is injected is formed between non-adhesive thin film layer 125 on lower substrate 124 and upper substrate 123, as shown in Fig. 9. With this microchannel chip 120, if a sterilization process is performed in the state of Fig. 8 after microchannel chip 120 is manufactured, the inside of microchannel 121 can be kept sterilized until immediately before the sample is injected into microchannel 121.
[0008] Furthermore, by using a microvalve 140 shown in Figs. 10 and 11 described in Patent Document 2 for controlling the amount of liquid sample injected into the microchannel 131, the microchannel 131 of the microchannel chip 130 can be opened and closed to isolate the microchannel 131 from the outside air until the sample is injected, thereby making the microchannel 131 in a sterilized state.
[0009] Microvalve 140 attached to upper substrate 132 of micro-channel chip 130 is formed by stacking a first sheet member 141 and a second sheet member 142 that is relatively thinner than first sheet member 141, and a recess 144 communicating with air channel 143 is formed between first sheet member 141 and second sheet member 142. As shown in FIG. 10, in a free state in which the two stacked first sheet members 141 and second sheet members 142 are not subjected to an external force, the two stacked first sheet members 141 and second sheet members 142 are inserted from upper substrate 132 so as to cross microchannel 131, and microchannel 131 is blocked by microvalve 140.
[0010] When injecting a sample into the microchannel 131, pressurized air is sent from the air channel 143 into the recess 144, causing the recess 144 between the first sheet member 141 and the second sheet member 142 to bulge. As a result, as shown in Fig. 11, the relatively thin second sheet member 142 curves more than the first sheet member 141 at the portion of the recess 144, and the overlapping first sheet member 141 and second sheet member 142 are curved as a whole, forming a gap through which the sample is injected into the microchannel 131.
[0011] Therefore, with this micro-channel chip 130, by controlling the microvalve 140 to be closed and performing the sterilization process in the state shown in FIG. 10 where the micro-channel 131 is blocked, and controlling the microvalve 140 to be open when injecting a sample, the inside of the micro-channel 131 can be kept in a sterilized state until just before the sample is injected into the micro-channel 131. [Prior art documents] [Patent documents]
[0012] [Patent Document 1] International Publication No. WO2007 / 094254 [Patent Document 2] JP 2007-248218 A Summary of the Invention [Problem to be solved by the invention]
[0013] In conventional micro-channel chip 120, when upper substrate 123 and lower substrate 124 are laminated to form micro-channel chip 120, non-adhesive thin film layer 125 that matches the minute width of micro-channel 121 must be formed, and micro-channel chip 120 cannot be manufactured using a general-purpose manufacturing process.
[0014] In addition, each time a sample is injected from the tip of tube 110 into microchannel 121, positive pressure must be applied from tube 110 to through-hole 122 of microchannel chip 120 to form the space of microchannel 121. Furthermore, since pressurized air is applied between integrated lower substrate 124 and upper substrate 123, there is a risk that upper substrate 123 will peel off from lower substrate 124 at the edge of non-adhesive thin film layer 125, causing the sample to leak out from the gap between them or that the solvent of the adhesive bonding lower substrate 124 and upper substrate 123 will enter microchannel 121.
[0015] Furthermore, when the sample is injected into the microchannel 121, the microchannel 121 is also pressurized, so that the reaction or change of the sample under atmospheric pressure cannot be observed.
[0016] In order to sterilize microchannel 131 using microchannel chip 130 described in Patent Document 2, microvalve 140 with a complex structure must be inserted through upper substrate 132 and positioned so as to partially block microchannel 131. This makes the structure of the entire microchannel chip 130 complex, making it extremely difficult to manufacture microchannel chip 130 having microchannel 131 with a very small width and length.
[0017] In addition, a pressurizing means is required to send pressurized air from air flow path 143 to recess 144, and as with micro-flow path chip 120, each time a sample is injected into micro-flow path 131, it is necessary to send pressurized air to recess 144 using the pressurizing means, which is cumbersome.
[0018] The present invention has been made in consideration of such conventional problems, and has an object to provide a microchannel chip adaptor that can perform a sterilization treatment on a microchannel chip of a common structure and maintain the microchannel in a sterilized state.
[0019] Another object of the present invention is to provide an adaptor for a micro-channel chip that enables a sample to be injected from a pipette into a micro-channel in a sterilized state by simply inserting the sample from the tip of the pipette into a connecting hole. [Means for solving the problem]
[0020] In order to achieve the above object, the microchannel chip adaptor according to claim 1 comprises a cylindrical body through which a connecting hole for supporting a tip of a pipette passes, A micro-channel chip adaptor that is in close contact with a periphery of an opening of a through-hole on a surface of a micro-channel chip at a position where a connecting hole communicates with a through-hole communicating with a micro-channel of the micro-channel chip, and that allows a sample to be injected from a pipette into the micro-channel, The cylindrical body is made of PDMS (polydimethylsiloxane) and is molded into a cylindrical shape with a connecting hole that passes through it, allowing the tip of a pipette to pass through freely. Less than 0.1mm The thickness shields the connecting holes The microchannel is then sealed off from the outside. The present invention is characterized in that a thin film that is connected to the connecting hole of the cylindrical body is formed integrally with the inner wall surface of the connecting hole.
[0021] The microchannel is sealed off from the outside by simply attaching the adapter, whose connecting hole is covered with a thin film, to the periphery of the through-hole on the surface of the microchannel chip. Therefore, if a sterilization process is performed for each microchannel chip to which the adapter is attached, the microchannel can be maintained in a sterilized state.
[0022] The thin film that shields the connection hole is used to insert the tip of the pipette into the connection hole. Easily penetrable, less than 0.1 mm Because of its thickness, a sample can be injected into the sterilized microchannel from the tip of a pipette simply by inserting it into the connecting hole.
[0023] The thin film formed integrally with the cylindrical body made of PDMS (polydimethylsiloxane) is elastically deformable, so that the thin film penetrated by the tip of the pipette adheres closely to the outer surface of the pipette. Even when a sample is injected by applying injection pressure from the pipette, the sample does not leak out from the gap between the pipette and the connecting hole.
[0024] The cylindrical body, molded from PDMS (polydimethylsiloxane), an elastic thermosetting resin, is resistant to sterilization treatment in which it is heated and pressurized together with the microchannel chip.
[0025] The microchannel chip adapter described in claim 2 is characterized in that a step is formed in the connecting hole to separate a small diameter hole that opens to the bottom surface of the cylindrical body and a large diameter hole that opens to the flat surface, and the thin film is integrally formed on the inner wall surface of the connecting hole along the step.
[0026] By abutting the step against the outer circumferential surface of the pipette to be inserted into the connecting hole, the insertion position of the pipette can be determined before the tapered tip of the pipette reaches the bottom surface of the microchannel.
[0027] If the core and cavity of the mold are opposed to each other at the position where the step that separates the small diameter hole and the large diameter hole is to be formed, a thin film can be integrally formed along the step between them.
[0028] The microchannel chip adaptor according to claim 3 is characterized in that a tapered surface is formed on the inner wall surface of the connecting hole, tapering the connecting hole from the opening through which the tip of the pipette is inserted toward the thin film.
[0029] Even if the insertion direction of the pipette into the connecting hole does not coincide with the vertical direction of the thin film, the tip of the pipette is guided toward the thin film along the tapered surface.
[0030] The microchannel chip adapter described in claim 4 is characterized in that it further comprises a flange plate integrally molded on the outside along the bottom surface of the cylindrical body, and the bottom surface of the flange plate is formed in a suction cup shape that is gently curved toward the opening on the bottom side of the connecting hole.
[0031] Due to the elasticity of the PDMS, the flange plate acts as an adhesive plate that closely attaches the adapter to the surface surrounding the through-hole opening.
[0032] The flange plate that is attached to the surface of the microchannel chip and the cylindrical body are connected together with PDMS, an elastic material. Therefore, even if the insertion direction of the pipette does not match the central axis direction of the connecting hole of the cylindrical body, the cylindrical body will tilt in accordance with the insertion direction of the pipette, allowing the pipette to be easily inserted into the connecting hole without damaging the cylindrical body.
[0033] Furthermore, even if the cylindrical body is tilted relative to the flange plate that is adsorbed to the surface of the micro-channel chip, when the external force on the cylindrical body is released, it returns to an upright position on the surface of the micro-channel chip, and the pipette inserted into the connecting hole is supported in an upright position relative to the surface of the micro-channel chip. Effect of the Invention
[0034] According to the invention of claim 1, by simply fitting the adapter to the periphery of the opening of the through-hole on the surface of the micro-channel chip, the micro-channel is isolated from the outside and sealed, and by carrying out a sterilization treatment on the micro-channel chip to which the adapter is fitted, the micro-channel is maintained in a sterilized state until immediately before the sample is injected.
[0035] The adapter is made of PDMS (polydimethylsiloxane), a thermosetting resin, so it will not deform or discolor even when heated and pressurized together with the microchannel chip.
[0036] Furthermore, when injecting a sample into the microchannel, the tip of a pipette can be inserted into the connecting hole of the adapter and the tip can be pierced through the thin film to inject the sample into the sterilized microchannel.
[0037] When a sample is injected from the tip of the pipette, the thin film that the tip of the pipette penetrates adheres closely to the outer surface of the pipette, so that even when injection pressure is applied to inject the sample, the sample does not leak out from the gap between the pipette and the connecting hole.
[0038] In addition, because the cylindrical body is molded using PDMS as the molding material, the state of sample delivery from a pipette to the microchannel can be observed through the semi-transparent microchannel chip adaptor.
[0039] The microchannel chip adapter, in which a thin film is integrally formed on the inner wall surface of the connecting hole that supports the pipette, can be mass-produced by molding using a mold.
[0040] According to the invention of claim 2, problems such as the tapered tip of the pipette coming into contact with the bottom surface of the microchannel and damaging the microchannel, or the tip of the pipette being covered by the bottom surface of the microchannel and making it impossible to inject a sample into the microchannel do not occur.
[0041] Furthermore, since the step and thin film separating the small and large diameter holes are formed along the same plane, the molding surface of the mold for molding the step and thin film is flat and free of irregularities, allowing the shape of the mold to be simplified.
[0042] According to the invention of claim 3, even if the insertion direction of the pipette into the connecting hole does not coincide with the vertical direction of the thin film, the tip of the pipette is guided toward the thin film along the tapered surface and reliably penetrates the thin film.
[0043] According to the invention of claim 4, the flange plate acts as an adsorption plate and adheres closely to the periphery of the opening of the through-hole, so that the sample does not leak out from the periphery of the opening of the through-hole.
[0044] Furthermore, since the micro-channel chip adapter is attached to the surface of the micro-channel chip without using adhesive, the solvent or adhesive components contained in the adhesive do not mix with the sample passing through the connecting holes or through-holes.
[0045] Furthermore, by simply pressing the adapter against the surface of the microchannel chip where the through-hole communicating with the microchannel is opened, the microchannel can be sealed off from the outside.
[0046] Furthermore, the flange plate can be attached by suction to the periphery of the opening on the surface where the through-holes of the micro-channel chip are opened, and the micro-channel chip adapter can be attached in a tight contact manner. Therefore, a general-purpose shaped micro-channel chip adapter can be attached to micro-channel chips of various shapes having different positions and numbers of microchannels and different positions and numbers of through-holes, thereby isolating the microchannels from the outside. [Brief description of the drawings]
[0047] [Figure 1]1 is a longitudinal sectional view showing a micro-channel chip adapter 1 and a micro-channel chip 20 according to a first embodiment of the present invention. [Diagram 2] 1 is a longitudinal cross-sectional view showing a state in which micro-channel chip adapters 1, 1 are closely attached to the periphery of injection hole 22a and discharge hole 22b of micro-channel chip 20, respectively. [Diagram 3] 1 is a longitudinal sectional view showing a state in which tip 25a of pipette 25 is inserted through thin film 2 of micro-channel chip adaptor 1. FIG. [Figure 4] FIG. 2 is a perspective view of the micro-channel chip adapter 1 as viewed from the bottom side. [Diagram 5] 2 is a longitudinal cross-sectional view of a main portion showing a core 31 and a cavity 32 of a mold 30 for molding a micro-channel chip adaptor 1. FIG. [Figure 6] 1 is a longitudinal cross-sectional view showing a micro-channel chip adapter 10 according to a second embodiment of the present invention attached to a micro-channel chip 20. FIG. [Figure 7] 1 is a longitudinal sectional view showing a state in which tip 25a of pipette 25 is inserted through thin film 11 of micro-channel chip adaptor 10. FIG. [Figure 8] FIG. 1 is a longitudinal sectional view of a conventional micro-channel chip adaptor 100. [Figure 9] 1 is a longitudinal sectional view of a micro-channel chip adaptor 100 in which a micro-channel 121 is formed. [Figure 10] FIG. 1 is a vertical cross-sectional view of a conventional micro-channel chip 130 in which a microvalve 140 is controlled to be closed. [Figure 11] FIG. 11 is a vertical cross-sectional view of micro-channel chip 130 in which microvalve 140 is controlled to be open. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0048] A micro-channel chip adapter 1 according to a first embodiment of the present invention will be described below with reference to Figs. 1 to 5. In the following description of the present specification, the direction shown in Fig. 1 is the up-down direction. This micro-channel chip adapter 1 is used to connect a pipette 25 that discharges or draws in a trace amount of sample such as an organic compound or a biological sample from a tip 25a to a micro-channel chip 20 that mixes, reacts, synthesizes, extracts, separates, and analyzes a sample injected into a micro-channel 21 having a width and depth of 500 nm to 1 mm.
[0049] The microchannel chip 20 is formed by attaching a lower substrate 24 made of PDMS having the same contour as the upper substrate 23 to one side of the upper substrate 23, on which the microchannel 21 of the upper substrate 23 is exposed. The upper substrate 23 is made of PDMS (polydimethylsiloxane) and has a groove that constitutes the microchannel 21 on the underside and a plurality of through holes 22, 22 that penetrate from the upper substrate to the groove from the upper side. The microchannel 21 has a width and depth of 500 nm to 1 mm and is formed between the upper substrate 23 and the lower substrate 24, which are laminated integrally one above the other. The microchannel 21 is sealed off from the outside and is connected to the plurality of through holes 22, 22 that open on the surface 23a of the upper substrate 23.
[0050] The adapter 1 for microchannel chips comprises a cylindrical tubular body 4 having a connecting hole 3 formed vertically for inserting a tapered pipette 25, and a flange plate 5 formed integrally with the outside of the cylindrical body 4 along the bottom surface 4a thereof and having a circular outline, which are integrally molded by injection molding using a mold 30 described below, using PDMS (polydimethylsiloxane) as the molding material.
[0051] As shown in FIG. 1, the connecting hole 3, which is a cylindrical hole that penetrates the cylindrical body 4 along the central axis in the vertical direction, has a large diameter portion 3a that opens at the top of the cylindrical body 4 and is large enough to allow a pipette 25 to be inserted from above, and a small diameter hole 3b that opens at the bottom and is narrower than the large diameter portion 3a and has an inner diameter that abuts against the intermediate outer peripheral surface of the tapered pipette 25, which are formed along the same vertical axis, and the large diameter portion 3a and the small diameter hole 3b are separated by a step portion 3c between them.
[0052] In this embodiment, the thin film 2 is formed integrally with the inner wall surface of the small diameter hole 3b along the step portion 3c, and the large diameter portion 3a and the small diameter hole 3b are separated by the thin film 2. The thickness of the thin film 2 is set so that it can be easily broken by the tip 25a of the pipette 25 inserted into the connecting hole 3, and the thin film 2 made of PDMS has a thickness of 0.1 mm or less.
[0053] Flange plate 5 is formed in an annular shape around the central axis of connecting hole 3 in cylindrical main body 4, and bottom surface 5a thereof is formed in a suction cup shape that curves gently upward toward the central axis of connecting hole 3. By making bottom surface 5a of flange plate 5 shaped like a suction cup, when the center of micro-channel chip adapter 1 in an upright position of cylindrical main body 4 is pressed toward the opening of through-hole 22 of micro-channel chip 20, flange plate 5 acts as a suction plate at the position where connecting hole 3 of cylindrical main body 4 and through-hole 22 of micro-channel chip 20 communicate with each other, and micro-channel chip adapter 1 is attached in close contact with surface 23a around the opening of through-hole 22.
[0054] This microchannel chip adaptor 1 is formed by injection molding using a mold 30 shown in FIG. 5 using PDMS as a molding material, and is integrally formed with a cylindrical tubular body 4 having connecting holes 3a and 3b formed vertically, a thin film 2 blocking a part of the connecting hole 3, and a flange plate 5. That is, as shown in FIG. 5, the large diameter hole 3a of the connecting hole 3 is formed by a protrusion 32a on the cavity 32 side, and the small diameter hole 3b is formed by a protrusion 31a on the core 31 side, and a thin film 2 having a thickness of 0.1 mm or less is formed in the gap between the protrusions 32a and 31a. This allows the thin film 2 blocking a part of the connecting hole 3 to be formed by a mold 30 having a simple structure consisting of a core 31 and a cavity 32, without using a complicated mold structure such as a slide mold. The molding of the microchannel chip adaptor 1 using a mold may be performed by various other molding methods such as transfer molding and compression molding in addition to injection molding.
[0055] 2, in this embodiment, micro-channel chip adapters 1, 1 molded in the same shape are attached in close contact with surface 23a surrounding the openings of injection hole 22a and discharge hole 22b, which are a pair of through holes 22, 22 communicating with both sides of micro-channel 21. As a result, the openings of injection hole 22a and discharge hole 22b, through which micro-channel 21 communicates with the outside, are covered by micro-channel chip adapters 1, 1 that are in close contact with surrounding surface 23a. Because communication hole 12 of micro-channel chip adapters 1, 1 is blocked by thin film 2, the inside of micro-channel 21 is sealed off and completely blocked from the outside.
[0056] By subjecting the microchannel chip 20 to a sterilization treatment such as ultraviolet irradiation, radiation irradiation, electron beam irradiation, corona discharge irradiation, plasma irradiation, steam pressure sterilization (autoclave), etc., the inside of the microchannel 21 can be maintained in a sterilized state until immediately before a sample is injected into the microchannel 21 of the microchannel chip 20.
[0057] According to the micro-channel chip adaptor 1 of this embodiment, flange plate 5 of micro-channel chip adaptor 1 mass-produced to the same shape acts as an adsorption plate, and sterilization can be performed with micro-channel 21 sealed by simply pressing micro-channel chip adaptor 1 against each opening of injection hole 22a and discharge hole 22b for various micro-channel chips 20 having different numbers and opening positions of injection hole 22a and discharge hole 22b.
[0058] When injecting a sample from pipette 25 into microchannel 21 of microchannel chip 20, tip 25a of pipette 25 is inserted into large-diameter hole 3a of microchannel chip adapter 1 attached around injection hole 22a, and pipette 25 is pushed in until the tapered outer circumferential surface of the middle of pipette 25 abuts against step 3c separating large-diameter hole 3a and small-diameter hole 3b, as shown in Fig. 3. In this state, tip 25a of pipette 25 penetrates thin film 2 and is inserted into small-diameter hole 3b. Small-diameter hole 3b is in communication with microchannel 21 via injection hole 22a, so that the sample can be injected into sterilized microchannel 21 by discharging the sample from tip 25a of pipette 25.
[0059] Since the cylindrical tubular body 4 and flange plate 5 of the micro-channel chip adaptor 1 are molded from an elastic material made of PDMS, even if the pipette 25 is inserted in an orientation inclined with respect to the axial direction of the connecting hole 3 of the micro-channel chip adaptor 1, the cylindrical body 4 bends following the insertion direction of the pipette 25, and the tip 25a of the pipette 25 can penetrate the thin film 2, and when the external force on the pipette 25 is released, the cylindrical body 4 returns to an orientation standing vertically with respect to the surface 23a of the micro-channel chip 20, and can support the pipette 25 inserted in the connecting hole 3 along the vertical direction. Therefore, when injecting a sample into the micro-channel 21, the multiple pipettes 25 can be held in a state inserted into the connecting hole 3 of the micro-channel chip adaptor 1 without having to hold them by hand.
[0060] Furthermore, the sample injected from tip 25a of pipette 25 into microchannel 21 does not leak out toward the large diameter hole 3a of connecting hole 3, because thin film 2 made of elastic material PDMS, through which pipette 25 is inserted, makes ring-shaped elastic contact with the outer peripheral surface of the middle of pipette 25. Even if a predetermined injection pressure is applied from pipette 25 to inject the sample into microchannel 21, the sample will not leak out from the opening of connecting hole 3.
[0061] When injecting a sample from a pipette 25, a thin and long tool such as a pipette 25 may be used to break the thin film 2 of the microchannel chip adapter 1 attached around the discharge hole 22b, thereby connecting the discharge hole 22b to the outside.
[0062] Next, a micro-channel chip adaptor 10 according to a second embodiment of the present invention will be described with reference to Figures 6 and 7. In the description of the second embodiment, components that are the same as or function similarly to those in the first embodiment will be given the same reference numbers and detailed descriptions thereof will be omitted.
[0063] Microchannel chip adapter 10 is made of a cylindrical tubular body 13 in which connecting hole 12 for inserting tapered pipette 25 is formed along the vertical central axis, and tubular body 13 is injection molded using PDMS as the molding material in a die consisting of a core and a cavity with the parting line corresponding to thin film 11 in the figure. This tubular body 13 may also be molded by various other molding methods such as transfer molding, compression molding, etc., in addition to injection molding.
[0064] When molding the cylindrical body 13, the molding surface of the core mold for molding the bottom surface 13a of the cylindrical body 13 is a mirror surface having an arithmetic mean roughness Ra of 500 nm or less, preferably 300 nm or less. The molding material for forming the bottom surface 13a of the cylindrical body 13 is PDMS, which has high fluidity in the mold, and therefore has excellent transferability to the molding surface of the mold that has been processed to a mirror surface, and the bottom surface 13a of the cylindrical body 13 can also be a mirror surface that is approximately equal to the arithmetic mean roughness Ra of the molding surface. In addition, as described later, in order to firmly integrate the micro-channel chip adapter 10 with the surface 23a of the micro-channel chip 20, the surface 23a of the upper substrate 23 to which the micro-channel chip adapter 10 is fixed is also molded with the molding surface of the mold that has been similarly processed to a mirror surface.
[0065] 6, the connecting hole 12 is composed of a large diameter hole 12a in the shape of an inverted truncated cone whose inner wall surface forms a tapered surface 12a1 that expands in diameter toward the top, and a cylindrical small diameter hole 12b that opens below the large diameter hole 12a to the bottom surface 13a of the cylindrical body 13. The lower end of the large diameter hole 12a and the small diameter hole 12b have the same inner diameter, and the large diameter hole 12a and the small diameter hole 12b, which are formed on the same vertical axis, are separated by a thin film 11 having a thickness of 0.1 mm or less that is integrally formed on the inner wall surface of the upper end of the small diameter hole 12b and that can easily pass the tip 25a of a pipette 25 inserted into the connecting hole 12.
[0066] In the micro-channel chip adapter 10 configured in this manner, the bottom surface 13a of the cylindrical body 13, which is in an upright position along the vertical direction, is closely attached to the surface 23a of the micro-channel chip 20 centered on the opening of the through-hole 22, and the micro-channel chip adapter 1 is integrally joined to the surface 23a around the opening of the through-hole 22.
[0067] In this embodiment, the bottom surface 13a of the cylindrical body 13 to be joined and the peripheral surface 23a of the micro-channel chip 20 where the through-holes 22 are opened are subjected to a surface modification treatment in advance by irradiating plasma, and then the bottom surface 13a of the cylindrical body 13 in an upright position is brought into close contact with the peripheral surface 23a where the through-holes 22 are opened, and the two are joined together. In the joining step, the bottom surface 13a of the cylindrical body 13 and the surface 23a of the micro-channel chip 20, which serve as the joining surfaces, are mirror-finished to have an arithmetic mean roughness Ra of 300 nm or less, as described above, so that all of these surface-modified joining surfaces that face each other and come into contact with each other are tightly adhered to each other without any gaps, and as a result, the bottom surface 13a of the cylindrical body 13 and the surface 23a of the micro-channel chip 20 are evenly and firmly integrated.
[0068] The plasma treatment in which plasma is irradiated may be either a vacuum plasma treatment or an atmospheric pressure plasma treatment. In addition, the treatment for modifying the surface of the bonding surface may be, in addition to the plasma treatment, a vacuum ultraviolet ray (VUV) treatment in which vacuum ultraviolet ray (VUV) is irradiated from an excimer lamp to the bonding surface, a corona discharge treatment, or the like.
[0069] As shown in Figure 6, when micro-channel chip adapter 10 is attached in an upright position to surrounding surface 23a where through-hole 22 of micro-channel chip 20 opens, small-diameter hole 12b of connecting hole 12 of micro-channel chip 20 communicates with micro-channel 21 via through-hole 22 of micro-channel chip 20. However, since connecting hole 12 is blocked by thin film 11, the inside of micro-channel 21 is sealed and completely isolated from the outside.
[0070] Therefore, by subjecting microchannel chip 20 to a microchannel chip adapter 10 attached thereto to a sterilization treatment such as ultraviolet irradiation, radiation irradiation, electron beam irradiation, corona discharge irradiation, plasma irradiation, steam pressure sterilization (autoclave), or the like, the inside of microchannel 21 can be maintained in a sterilized state until immediately before a sample is injected into microchannel 21 of microchannel chip 20.
[0071] When injecting a sample from pipette 25 into microchannel 21 of microchannel chip 20, tip 25a of pipette 25 is inserted into large diameter hole 12a of microchannel chip adaptor 10, as shown in Fig. 7. Since the inner surface of large diameter hole 12a is tapered surface 12a1 that slopes toward thin film 11, when pipette 25 is pushed further downward within large diameter hole 12a, tip 25a is guided by tapered surface 12a1, penetrates thin film 11 and is inserted into small diameter hole 12b.
[0072] In this state, the inner diameter of small diameter hole 12b is approximately equal to the outer diameter of the middle part of pipette 25, which is formed to have a downward tapered shape, so that tip 25a of pipette 25 is positioned within small diameter hole 3b of connecting hole 12 before reaching microchannel chip 20.
[0073] The small diameter hole 12b into which the tip 25a of the pipette 25 is inserted is connected to the microchannel 21 via the through hole 22 (injection hole 22a), so that the sample can be injected into the sterilized microchannel 21 by ejecting the sample from the tip 25a of the pipette 25.
[0074] The area around connecting hole 12 of cylindrical body 13 into which tip 25a of pipette 25 is inserted and through hole 22 which communicates with the connecting hole is integrated with surface-modified bottom surface 13a of cylindrical body 13 and surface 23a of micro-channel chip 20 in close contact with each other without any gaps, so that even when a predetermined injection pressure is applied from pipette 25 to inject a sample into micro-channel 21, the sample will not leak out from the gap between micro-channel chip adapter 10 and surface 23a of micro-channel chip 20.
[0075] Furthermore, the sample injected from tip 25a of pipette 25 into microchannel 21 does not leak out toward larger diameter hole 12a of connecting hole 12, because thin film 11 made of elastic PDMS material through which pipette 25 is inserted makes ring-shaped elastic contact with the outer peripheral surface of the middle of pipette 25. Even if a predetermined injection pressure is applied from pipette 25 to inject the sample into microchannel 21, the sample does not leak out from the opening of connecting hole 12.
[0076] Even in this embodiment, when micro-channel chip 20 has discharge hole 22b communicating with micro-channel 21, micro-channel chip adaptor 10 may be attached around the opening of discharge port 22b, and when a sample is injected from pipette 25, thin film 11 of micro-channel chip adaptor 10 may be broken using a long and thin tool such as pipette 25 to connect discharge hole 22b to the outside.
[0077] In the above-described first and second embodiments, when a sample is injected from tip 25a of pipette 25 into microchannel 21, tip 25a of pipette 25 is pierced through thin film 2, 11 of microchannel chip adapter 1, 10 attached around the opening of injection hole 22a to break thin film 2, 11; however, an opening may be formed in thin film 2, 11 in advance with a long and thin jig, and then pipette 25 may be inserted into connecting hole 12 and a sample may be injected from tip 25a.
[0078] Moreover, the thin films 2, 11 may be provided at any positions of the connecting holes 3, 12 as long as they block the connecting holes 3, 12.
[0079] Furthermore, in each of the above-described embodiments, the micro-channel chip adapters 1, 10 are attached in a state of intimate contact with the surface 23a of the micro-channel chip 20 using the flange plate 5 or a surface modification process, but the micro-channel chip adapters 1, 10 may also be attached in intimate contact with the surface 23a around the opening of the through-hole 22 of the micro-channel chip 20 using a double-sided tape or adhesive having adhesive layers on both sides. [Industrial Applicability]
[0080] INDUSTRIAL APPLICABILITY The present invention is suitable for a micro-channel chip adaptor that is attached to a micro-channel chip in order to inject a sample from a pipette into a micro-channel of the sterilized micro-channel chip. [Explanation of symbols]
[0081] 1, 10 Microfluidic Chip Adapter 2, 11 Thin Films 3, 12 connecting hole 20 Microfluidic Chip 21 Microchannel 22 Through hole 25 Pipettes
Claims
1. A pipette tip is supported by a connecting hole extending through a cylindrical body. a micro-channel chip adaptor that is in close contact with a periphery of an opening of a through-hole on a surface of a micro-channel chip at a position where the connecting hole is in communication with a through-hole that is in communication with a micro-channel of the micro-channel chip, and allows a sample to be injected from the pipette into the micro-channel, The cylindrical main body is molded into a cylindrical shape with the connecting hole passing therethrough using PDMS (polydimethylsiloxane) as a molding material, a thin film having a thickness of 0.1 mm or less, through which the tip of the pipette can be freely passed, that blocks the connecting hole and seals the microchannel by isolating it from the outside, is integrally formed on an inner wall surface of the connecting hole of the cylindrical main body.
2. A step portion is formed in the connecting hole to separate a small diameter hole that opens to the bottom surface of the cylindrical main body and a large diameter hole that opens to a flat surface, 2. The micro-channel chip adaptor according to claim 1, wherein the thin film is integrally formed on an inner wall surface of the connection hole along the step portion.
3. 3. The microchannel chip adaptor according to claim 1, wherein an inner wall surface of the connecting hole is formed with a tapered surface that tapers the connecting hole from an opening into which the tip of the pipette is inserted toward the thin film.
4. The cylindrical body further includes a flange plate integrally formed on the outside along the bottom surface thereof, 4. The micro-channel chip adaptor according to claim 1, wherein the bottom surface of the flange plate is formed in a suction cup shape that is gently curved toward the opening on the bottom side of the connection hole.
Citation Information
Patent Citations
microchip
JP2007248218A
Inspection system and liquid feeding device used in the same
JP2012159358A
Microfluidic cartridge with pipetting operation guide
JP2017523412A
Adapter
JP2019203806A
Microchannel chip and method for manufacturing such chip
WO2007094254A1