JP2011214984A - Microchip assembly - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a microchip assembly that uniformizes the levelness and the liquid height of a liquid level, performs accurate measurement without causing measurement errors, minimizes evaporation of a sample liquid, can be also applied to measurement of a sample which requires a relatively long time, and further, can readily collect and clean the sample liquid, and to attain an alternative device for measuring a trace amount where evaporation of the liquid sample and uniformity of a liquid level are problems.SOLUTION: The microchip assembly includes a hard baseplate including a hole; a chip adaptor including a hole installed on an upper surface of the baseplate; a transparent plate that is installed on an upper surface of the chip adaptor to block the hole and is made of a high light-transmitting material; and a microchip that is installed on an upper surface of the transparent plate, and includes a dent, facing upward and a plurality of sample liquid injection holes in line with the dent on a lower surface. By placing the microchip on the transparent plate, a microcavity that is filled with a sample liquid between an upper surface of the transparent plate and the dent of the microchip is formed.

Description

  The present invention relates to a microchip assembly suitable for optically measuring the absorbance of a small amount of liquid sample.

  Conventionally, various techniques for optically measuring a small amount of a liquid sample using a microplate have been proposed, but all of them are based on the level of liquid level or the liquid surface due to the viscosity of the liquid sample, the hydrophilicity of the microplate material, the surface tension, etc. The height (optical path length) of the liquid became non-uniform, and as a result, the measurement results varied and the measurement could not be performed accurately.

As a method for solving these problems, for example, the following Patent Document 1 has been proposed.
Patent Document 1 describes an invention in which a sample liquid is held by surface tension in a micro cuvette 7 formed between opposed cuvette surfaces 3 and 5.

  Although the present invention is presumed to be effective for holding the liquid volume 8, the collection of expensive samples required for this type of optical measuring device, the measurement that requires a relatively long time, and the cleaning of the microchip As for such things, it is not complete.

JP 2009-85958 A

  That is, in Patent Document 1, since the micro cuvette 8 that opens the sample solution in the lateral direction is injected, it is impossible to collect an expensive or precious liquid sample, and the outer periphery of the micro cuvette 8. Since the portion is open, the micro sample liquid in the micro cuvette 8 evaporates in a short time, which is not suitable for time-consuming measurements.

  Focusing on the above-mentioned problems, the present invention makes the liquid level level and liquid level uniform, can accurately measure without causing measurement errors, minimizes evaporation of the sample liquid, and takes a relatively long time. It is an object of the present invention to provide a microchip assembly that can be applied to the above-described measurement and that can easily collect and wash a sample solution.

  To achieve the above object, the present invention provides a hard base plate having a hole, a chip adapter having a hole installed on the upper surface of the base plate, and a high light installed on the upper surface of the chip adapter so as to close the hole. A transparent plate made of a permeable material, and a microchip which is installed on the upper surface of the transparent plate and has a concave portion directed upward on the lower surface and a plurality of sample liquid injection holes connected to the concave portion. By placing the microchip, a microcavity filled with the sample liquid is formed between the upper surface of the transparent plate and the recessed portion of the microchip.

  Since the present invention is configured as described above, the liquid level level and the liquid height are made uniform, accurate measurement is possible, and evaporation of the sample liquid can be minimized, so that it is possible to measure a sample that requires a relatively long time. Further, it is possible to provide a microchip assembly which can be applied and can easily collect and wash a sample solution.

  As a supplementary explanation, the microchip assembly has a flow path structure in which the optical path length is precisely defined, and one or more micro flow paths are provided, and the optical path length with a very small volume is defined. The concentration of the sample solution can be accurately measured optically. This microchip assembly has a secondary effect that it can be widely used as an adapter for micro sample measurement using a microplate reader if it has the same installation area as a standard microplate on the market. It is.

Sectional drawing which shows the principal part structure of the microplate assembly of one Example of this invention. FIG. 2 is an overall oblique view of the microplate assembly with the lid closed. The external appearance slope figure of the state which opened the lid same as the above. The top view of the state which closed the lid same as the above. CC sectional drawing in FIG. The top view of one microplate. VII-VII sectional drawing of FIG. The bottom view of FIG. 6 or the right side view of FIG. The enlarged view of the microchannel pattern shown in FIG. State diagram when supplying or recovering sample liquid in the configuration of the present invention The elements on larger scale of FIG.

The configuration of an embodiment of the present invention will be described below with reference to the drawings.
FIG. 1 is a cross-sectional view showing the configuration of the main part of the present invention, and FIGS.
In the figure, 1 indicates the entire microplate assembly. Reference numeral 2 denotes a base plate formed of a material such as metal, ceramics, or plastic having the same hardness, and is provided with a long hole 2A large enough to allow the irradiation light 17 to pass through. In this example, two long holes are provided in parallel. The elongated holes 2A may be provided with a number of holes corresponding to microchips to be described later. The base plate 2 has a recess 2B having a desired depth around the elongated hole 2A.

On the upper surface of the recessed portion 1B of the base plate 2, a chip adapter 10 having a slit 10A that is large enough to pass the irradiation light 17 and slightly smaller than the hole 2A is placed. The slits 10A are long enough to face eight microchips 11 described later from above.

  On the upper surface of the chip adapter 10, a deep recess 10A is formed at the center, and a shallow recess 10B connected to the outer periphery of the recess 10A is formed as shown in the figure. Of these concave portions, a quartz glass plate 9 that is hard and has high optical transparency is placed and fixed on the upper surface of the deep concave portion 10A inside. The thickness of the quartz glass plate 9 is made to coincide with the upper surface of the recessed portion 10A, and when the connected quartz glass plate 9 is placed and fixed on the recessed portion 10A, it is made to coincide with the bottom surface of the shallow recessed portion 10B. The quartz glass plate 9 does not necessarily have to be quartz glass, and can be replaced as long as the material has the same or similar properties.

  Reference numeral 11 denotes a PDMS chip placed over the quartz glass plate 9 and the bottom surface of the shallow recess 10B. PDMS is the Japanese name “Polydimethylsiloxane” and English name “Polydimethylsiloxane”, and is widely used in this industry for microchips, microfluidic chips, microchannels, and the like. Hereinafter, the PDMS chip 11 is simply referred to as a microchip. The material used in this example is made of a material equivalent to a hard silicone resin having a hardness of about 40 (IRHD) and has an extremely high light transmittance equivalent to that of quartz glass.

  Reference numeral 13 denotes a sample solution injection tube made of the same material as the microchip joined to the upper surface of the PDMS chip 11 by heat fusion. The sample is placed in the microcavity 20 formed by the recessed portion on the lower surface of the microchip 11 and the quartz glass 9. Used to introduce liquid 14. The configuration of the microchip 11 will be described later.

  Reference numeral 3 denotes a lid that can be freely opened and closed by a shaft 8 provided in the block 4, and is provided to prevent the microchip 11 from floating after the microchip 11 is set on the chip adapter 10. The lid 3 presses the microchip 11 against the upper surface of the quartz glass 9 with an appropriate pressure and functions so that liquid leakage does not occur from the microcavity 20. A thumb screw 5 for closing the lid 3 is screwed into a spacer 15 provided on the base plate 2. The lid 3 is provided with 16 holes 3A equal to the number of microchips 11 so that the microchips 11 can be seen from above. Reference numeral 6 denotes a measurement reference hole provided in the base plate 2 to enable reliable measurement.

  FIG. 2 shows a state where the thumbscrew 5 is screwed into the spacer 15 and the lid 3 is fixed to the base plate 2. The lid 3 is formed of metal or plastic. When the lid is closed, the microchip 11 is pressed against the upper surface of the quartz glass plate 9 with an appropriate pressure by its own elasticity, and the watertightness or airtightness of the microcavity 20 is maintained. Be drunk.

If the lid 3 is opened as shown in FIG. 3, the microchip 11 can be taken out and cleaning can be performed easily. FIG. 4 is a top view of the state in which the lid 3 is closed, and FIG.

Next, based on FIG. 6 thru | or FIG. 9, the structure of the microchip 11 is demonstrated in detail.
As described above, the microchip 11 is made of a plate material having a thickness of 1 millimeter made of a material such as PDMS or silicone resin. Since these materials have extremely high light transmittance, flexibility, and good adhesion, they are suitable for forming the microcavity 20 that requires hermeticity.

  A concave portion 11A directed upward is formed on the lower surface of the center portion of the microchip 11 formed of a plate. As described above, the concave portion 11A forms a microcavity 20 that becomes a liquid pool with the quartz glass plate 9. The bottom of the concave portion inevitably formed when the concave portion 11A is formed becomes the top plate 21 of the microchip. The top plate 21 should be made as thin as possible in order to increase light transmittance. In one embodiment of the invention, this thickness was 0.2 millimeter.

As shown in FIGS. 8 and 9, the concave portion 11 </ b> A has an oval shape without straight lines and corners, in other words, the top plate 21 has the same shape. Sample liquid injection holes 23 are formed in both ends of the top plate 21 in the longitudinal direction.
A sample solution is injected from the sample solution injection hole 23 with a pipette or the like and used for measurement. The sample liquid injection hole 23 should have a diameter as small as possible in order to suppress evaporation of the sample liquid, and is 1 mm in this embodiment.

Reference numeral 19 denotes a sample injection tube provided at the periphery of the sample liquid injection hole 23 of the top plate 21, which is made of the same material as that of the microchip 11 and is provided as shown in FIG. 7 by heat fusion by induction heating. . The sample injection tube 19 is not necessarily required when the sample liquid injection hole 23 has a relatively high rigidity. However, it can be easily understood that if the sample injection tube 19 is configured to face upward from the hole 3A of the lid 3, the sample liquid can be quickly and reliably injected by the pipette.
In addition, since the microcavity 20 is formed as shown in FIG. 9 as described above, the flow of the sample liquid is smooth, the liquid group is eliminated, and the sample liquid can be injected quickly and uniformly.

Next, a method for injecting and collecting the sample liquid will be described with reference to FIGS.
Reference numeral 12 denotes a pipette filled with a sample liquid. When the tip of the pipette 12 is inserted into the one sample injection tube 19 and the sample liquid is pushed out by operating the pipette, the sample liquid is filled into the microcavity 20. Is done. At this time, the other sample injection tube 19 is evacuated, and the sample liquid can be injected smoothly and rapidly.
If the irradiation light 17 is irradiated from above in this state, various physical properties such as absorbance of the sample solution can be measured. Reference numeral 30 denotes a detector that receives light that has passed through the sample liquid.

  FIG. 11 is an enlarged view of injecting the sample liquid. If the pipette is operated and suctioned, the sample liquid can be extracted from the microcavity, and an expensive and precious sample liquid can be recovered.

Further supplementary explanation is as follows.
That is, in the microchip assembly 1, as shown in FIG. 2, the microchip 11 is attached to the chip adapter 10 on which the quartz glass plate 9 is installed, and the chip adapter 10 is installed at the position of the guide pin 7 of the base plate 2. If the lid 3 is closed and the knob screw 5 is tightened, it can be used as a microchip assembly.

  In the microchip assembly 1, as shown in FIG. 6, a pipette 12 injects a liquid sample from the inlet 13 into a volume of 3 μL that fills the microcavity 20 of the microchip 11, and optical measurement is performed as shown in FIG. 7. To start.

As shown in FIG. 6, the liquid sample that has been measured can be sucked from the inlet 13 by the pipette 12 and collected.

Since the microcavity 20 on the bottom surface of the microchip 11 is opened, the unit of the microchip 11 including the chip adapter 10, the quartz glass plate 9, and the sample injection tube 19 is removed from the base plate 2, and the quartz glass plate 9 If the microchip 11 is separated and immersed in ethanol, it can be washed. Thereafter, if the moisture is dried, the quartz glass plate 9 and the microchip 11 can be used repeatedly, which is excellent in economic efficiency.

The microphone plate assembly of the present invention can be applied to the concentration measurement and fluorescence measurement of a target substance using a microplate reader.
In addition, this invention is not limited to the structure of one Example, It cannot be overemphasized that a various deformation | transformation example is also considered within a claim, and these are also included.

DESCRIPTION OF SYMBOLS 1 ... Microchip assembly 2 ... Base plate 3 ... Cover 4 ... Block 5 ... Knob screw 6 ... Measurement reference hole 7 ... Guide pin 8 ... Shaft 9 ... Quartz glass plate 10 ... Chip adapter 11 ... Microchip 12 ... Pipette 13 ... Sample inlet 14 ... Sample solution 15 ... Spacer 17 ... Irradiation light 18 ... Well pitch DESCRIPTION OF SYMBOLS 19 ... Sample liquid injection tube 20 ... Microcavity 21 ... Top plate 22 ... Side wall 23 ... Hole 24 ... Micro flow path pattern

Claims (9)

A rigid base plate having holes, a chip adapter having holes installed on the upper surface of the base plate, a transparent plate made of a highly light-transmitting material installed on the upper surface of the chip adapter so as to close the holes, and this transparent A microchip having a concave portion that is installed on the upper surface of the plate and that extends upward on the lower surface and a plurality of sample liquid injection holes that are continuous with the concave portion, and the microchip is placed on the transparent plate to place the transparent plate A microchip assembly in which a microcavity filled with a sample solution is formed between an upper surface and a recessed portion of a microchip. A quartz glass plate is placed on a metal plate with a hole, and the entire bottom surface of the microchannel is open and a transparent PDMS chip is pasted to the position of the metal plate with the hole. 2. The microchip assembly according to claim 1, wherein the upper surface of the chip has an integrated structure in which a cover for preventing lifting is covered. A liquid sample that is held by filling a liquid sample between quartz glass and a PDMS chip having substantially parallel surfaces in a forming relationship and filling the flow path, thereby providing an optical path for measuring absorbance. 2. The microchip assembly according to claim 1, wherein the microchip assembly is in a measurement state. 2. The microchip assembly according to claim 1, wherein the PDMS chip channel has no corners and is entirely curved. The microchip assembly according to claim 1, wherein the PDMS chip channel has only two very small diameter sample liquid inlets opened. 2. The microchip assembly according to claim 1, wherein the material of the PDMS chip is made of transparent silicone rubber and has high transmittance characteristics in a wide wavelength band from the ultraviolet region to the near infrared region. The sample inlet of the PDMS chip has a two-layer structure with silicone rubber with a hole in it, which enhances the compatibility with the pipette chip and makes it easy to determine the injection position of a trace liquid sample The microchip assembly according to claim 1. The microchip assembly according to claim 1, wherein the liquid sample recovery after the measurement can be easily performed by sucking with a pipette tip. 2. The microchip assembly according to claim 1, wherein a plurality of flow paths are formed in one PDMS chip, and a large number of trace liquid samples can be measured simultaneously.