JP4411390B2 - Micro liquid flow control method and control apparatus - Google Patents

Description

  The present invention relates to a microchip and a method for controlling a micro liquid flow in the microchip.

  Microchips for electrophoresis, chemical reaction, and analysis use thin channels with a diameter of several microns to hundreds of microns, and liquids such as water, various aqueous solutions, organic solvents, and various chemicals are contained inside. Put in and use. Such micro liquid flow control inside the microchip is very difficult.

  So far, several types of microvalves have been developed, such as those that use deformation of elastic materials such as rubber, those that physically move lid parts, and those that use negative pressure by a pump (Patent Document 1). These require an external driving gas pressure, and there are problems such that the junction with the microchip occupies a large area and the apparatus becomes large.

For example, in electrophoresis microchips, a charged sample is used, so a technique for electrically controlling the liquid flow or the sample in the liquid flow has been developed and put to practical use, but the high voltage is controlled in a complex manner. In addition, since the electrode installation space is large, there is a problem that the degree of freedom in designing the flow path is low.
JP 2004-33919 A

  An object of the present invention is to provide a micro liquid flow control technique that is simpler and suitable for miniaturization in microchips for electrophoresis, chemical reaction, analysis, and the like.

  The present invention relates to the following microchip and a micro liquid flow control method in the microchip.

  1. A microchip having at least one first microchannel in which a substance moves, a second microchannel crossing the first microchannel, and a bubble generation mechanism capable of generating bubbles in the second microchannel. A microchip capable of moving a substance in the first microchannel into the second microchannel by generating bubbles in the second microchannel.

  4). When the substance moves on at least one first microchannel and moves to the vicinity of the intersection of the first microchannel for mass transfer and the second microchannel capable of generating bubbles, the inside of the second microchannel A method for controlling a micro liquid flow in a microchip, wherein bubbles are generated in the micro chip and a substance existing in the vicinity of the intersection is introduced into the second micro channel.

Hereinafter, the present invention will be described in more detail.

  The microchip of the present invention can be used for applications such as electrophoresis, chemical reaction, and analysis.

  The microchip of the present invention has a first microchannel and a second microchannel that intersect each other. There may be one first microchannel or two or more microchannels. At least one first microchannel crosses the second microchannel.

  Each channel in the microchip can be used as a bioanalysis / sample processing channel, a chemical analysis channel, or the like.

  In the microchip, the first microchannel performs a substance movement.

  In one embodiment of the present invention, for example, in an electrophoresis microchip, an electrode is connected to both ends of a first microchannel, voltage is applied, and the first microchannel is separated according to properties such as charge and molecular weight. The target substance can be moved. The substance separated by electrophoresis is not particularly limited as long as it has a charge. For example, a substance derived from a living body such as nucleic acid (DNA, RNA), peptide, protein, mucopolysaccharide, phospholipid, plant extract, Alternatively, natural or synthetic physiologically active substances are widely exemplified.

  In another embodiment of the present invention, the chemical reaction chip is exemplified by a configuration in which substances involved in the reaction are supplied from both ends of the first microchannel, for example, and a reaction product is obtained in the first microchannel. . When there are a plurality of reagents, the number of first microchannels corresponding to the number of reagents can be formed, and a reaction product can be obtained at the intersection of the first microchannels.

  The microchip of the present invention may have a second microchannel, and further include a bubble generating means that can generate bubbles in the second microchannel.

  The first microchannel and the second microchannel are filled with liquid. Examples of the liquid include water, an aqueous solvent (a mixture of water and a water-miscible organic solvent), an organic solvent, an aqueous solution or an organic solvent solution in which an organic substance or an inorganic substance including a buffer solution is dissolved. The liquid generates bubbles by heating.

  The width or diameter of the first microchannel and the second microchannel is about 1 to 250 μm, preferably about 5 to 200 μm, more preferably about 10 to 150 μm.

  In a preferred embodiment of the present invention, as the bubble generating means, a heating element is provided at the periphery or the periphery of the second microchannel, preferably at a position in contact with the second microchannel, and the heating element is heated to locally In general, bubbles are generated in the vicinity of the heating element. The heating element may be a micro heater or a light absorber that absorbs light, particularly laser light. As the light to be irradiated, any light source having a wavelength of about 250 nm to 1200 nm can be used, visible light, ultraviolet light, infrared light, microwave, or the like can be used, and laser light is preferably used. Laser light is preferable because the liquid in the second microchannel can be heated in a narrow range from submicrometer to micrometer, and bubbles can be generated quickly.

The heating element may be provided at any position of the second microchannel. For example, the heating element may be provided at or near the intersection of the first microchannel and the second microchannel. The heating element moves a substance existing at or near the intersection by the pressure accompanying the generation of bubbles, and preferably moves from the intersection of the second micro flow path to the opposite side of the heating element (for example, the take-out tank 7 side in FIG. 2). Can be made.

  The heating element is capable of heating the liquid in the second microchannel to the extent that bubbles are formed, and is preferably capable of heating quickly to the boiling point or higher of the liquid. If the liquid can be heated quickly, the substance present at or near the intersection can be moved quickly. The time for heating from the start of heating to the boiling point of the liquid or higher is usually within 1 second, preferably 1 to 500 milliseconds, more preferably about 1 to 100 milliseconds. If the liquid in the second microchannel can be heated quickly by the heating element, it is preferable because the substance at or near the intersection can be moved without missing.

In a particularly preferred embodiment of the present invention, when the laser absorber installed near the wall surface of the second microchannel is irradiated with a strong pulse laser having a short peak of several tens of milliseconds or less, the temperature of the interface between the absorber and the liquid Rises rapidly and liquid evaporation occurs. Evaporation of the liquid is unlikely to occur and the energy density per one pulse of the laser is not 0.001J / cm ² or more, while, in the 3J / cm ² or more, occurs the evaporation of the absorber, sometimes impurities occurs. Therefore, in the present invention, the liquid is evaporated by irradiating the thin film type absorber installed in the flow path by using a pulse laser having a wavelength that transmits through the microchip body and converging the flow path size in the microchip. The micro liquid flow can be controlled. In addition, it is desirable that the laser beam to be irradiated has a wavelength such as 240 to 1200 nm that transmits light to some extent with respect to the liquid flow. For example, a 532 nm YAG double wave, a visible to near infrared wavelength laser diode, a 1064 nm YAG fundamental wave, a Yb fiber laser, a 248 nm KrF excimer laser, or the like can be used. When a pulse laser is used, the pulse width is not particularly limited as long as the laser absorber can be heated to a desired temperature for a desired time, but is preferably 50 femtoseconds to 500 milliseconds, more preferably 500 picoseconds to 100 milliseconds. Degree.

  In addition, the same effect as that of a pulse can be obtained by scanning a continuous output laser.

  When a laser having a wavelength of 240 to 400 nm is used, it is preferable to use a material that transmits the wavelength, such as quartz glass, as the main body constituting the microchip. If the wavelength of the laser is 400 to 1200 nm, quartz glass, ordinary glass, plastic, or the like can be used as the microchip body. The microchip can be obtained, for example, by stacking two or more plate-shaped materials (microchip body) having grooves corresponding to the first and second microchannels.

  In a preferred embodiment of the present invention, the material of the thin film type absorber that is a component of the bubble generation mechanism desirably has a laser wavelength absorbability and a high melting point, and includes iron, nickel, cobalt, chromium, and aluminum. Metals such as copper, zinc, tin, and alloys based on these, such as stainless steel, carbon steel, brass, white copper, aluminum alloys, and ceramics including alumina, zirconia, titania, silicon nitride, and silicon carbide Etc. can be raised.

  In a preferred embodiment, the micro liquid flow control method of the present invention is operated from the outside of the microchip using a laser, so that no complicated mechanism is required on the microchip side. Further, since the irradiation area is narrow, a laser having a small total output can be used, which is economical.

  In a particularly preferred embodiment of the present invention, it is desirable that a plurality of channels intersect at 10 o'clock or X-shape when performing microchannel control. Install an absorber in at least one channel and irradiate the laser to raise its internal liquid temperature to the boiling point or higher instantaneously (millisecond level), and part of the liquid in the other channel due to the pressure of the generated gas Can be led to another flow path. Furthermore, the energy density per single irradiation of the laser is preferably in the range of 0.001 J / cm 2 to 3 J / cm 2 on the absorber surface. By giving an output in this range, it is possible to evaporate only the liquid without damaging the absorber.

  In one particularly preferred embodiment of the present invention, the microchip is transparent to the laser, the heating element is a laser absorber, and the laser absorber generates heat when irradiated with a pulsed laser from outside the microchannel. It is characterized by that.

  If the microchip of the present invention is used, the liquid flow can be controlled by an external operation without installing a drive system on the microchip.

  Furthermore, the microchip of the present invention is characterized in that the laser is visible or near-infrared, and it is possible to use a laser that is small, inexpensive, and can be stably operated for a long time, such as a laser diode, and the size of the device can be reduced. Reduction is possible.

  According to the present invention, in a microchip for electrophoresis, a microchip for chemistry, and the like, a part of a sample can be easily guided to another channel or a part of the sample can be taken out. High functionality can be achieved.

  Hereinafter, the present invention will be described in detail with reference to examples. FIG. 1 is an overall view showing a concept of a micro liquid flow control device according to an embodiment of the present invention, and FIG. 2 is an enlarged view showing a main part of the micro liquid flow control device of the present embodiment.

  The microchip for electrophoresis of this example is one in which a part of a sample is taken out from the microchip. As shown in FIGS. 1 and 2, in the electrophoresis microchip 1, the sample is introduced into the first microchannel 3 near the electrode hole 2 and flows through the channel 3 toward the electrode hole 4. A mass distribution of the sample occurs along the flow path 3. The electrode holes 2 and 4 and the flow path 3 are filled with a liquid such as water or saline.

  In the present embodiment, a second micro flow path 6, a buffer tank 5 and a take-out tank 7 that intersect perpendicularly to the migration direction are provided in the middle of the flow path 3. The second microchannel 6 and the buffer tank 5 are filled with water or saline, but the take-out tank 7 is left empty. Laser light 11 output from the laser oscillator 9 at an appropriate timing, positioned and converged by the scanning device 10 and the lens 8 is irradiated to the laser absorber 12, and the liquid around the laser absorber 12 evaporates to form bubbles 13. Arise. By the pressure at this time, the liquid in the flow path 6 moves and the liquid 14 in the migration flow path 3 moves, so that only the sample 15 to be taken out can be guided to the take-out tank 7.

  The laser generator generates a pulse wave or a continuous laser beam. The laser wavelength is preferably selected in the range of 400 to 1200 nm, which is less attenuated by the microchip material and liquid. For example, an SHG-YAG laser (wavelength 532 nm), a laser diode (wavelength 400 to 1200 nm), a fundamental wave YAG laser (wavelength 1064 nm), a Yb fiber laser (wavelength 1070 to 1100 nm), or the like can be used. The laser beam is irradiated by scanning with pulses or continuous light, and the single irradiation time by pulse width or scanning is preferably about 10 milliseconds or less.

Although sufficient appropriate laser energy density to the evaporation occurs is material dependent, it has been found that to 0.001J / cm ² not in the range of 3J / cm ^2. The laser output is determined in consideration of the viscosity of the liquid used within this range.

1 is an overall view showing a concept of a micro liquid flow control device of an embodiment of the present invention. It is a figure which expands and shows the principal part of the micro liquid flow control apparatus of an Example.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Electrophoresis microchip 2 Electrode hole 3 Electrophoretic flow path 4 Electrode hole 5 Buffer tank 6 Sub flow path 7 Extraction tank 8 Condensing lens 9 Laser oscillator 10 Laser scanning device 11 Laser beam 12 Laser absorber 13 Bubble 14 Liquid 15 Extraction sample

Claims (3)

Substance bear one electrode holes 2 and one other electrode holes 4 moving, first microchannel filled with liquid, a buffer tank 5 filled with liquid which intersects perpendicularly with the first microchannel the second microchannel filled with liquid in which a blank extraction vessel 7, and made from the gas bubble generating mechanism capable of generating a bubble in the second microchannel, said bubble generating mechanism is a laser generator heating element the a, the heating element is provided within the second microchannel in the vicinity and the buffer tank 5 side of the intersection of the second microchannel and said first microchannel, the heating element is a laser generator it a micro chip with bubble generating mechanism, characterized in that can generate bubbles absorbs laser to heat the liquid in the second microchannel from the apparatus, the bubbles in the second microchannel due to the occurrence, The substance of the serial first microchannel can be moved to the extraction chamber 7 side of the second microchannel, the microchip.   The microchip according to claim 1, wherein the microchip is a microchip for electrophoresis, chemical reaction, or analysis. A microchannel control method using the microchip according to claim 1 or 2, wherein a substance connects one electrode hole 2 and another electrode hole 4 on a first microchannel filled with a liquid. A second micro flow filled with a liquid capable of generating bubbles, which is provided with a buffer tank 5 filled with a liquid and an empty take-out tank 7 perpendicularly intersecting the first micro flow path for mass transfer. When moving to the vicinity of the intersection of the road , the laser light is applied to the heating element provided in the second micro flow path and in the vicinity of the intersection and on the buffer tank 5 side in the submicrometer to micrometer range. characterized in that bubbles are generated by irradiating, characterized by guiding the substance present in the vicinity of intersection point extraction vessel 7 side of the second microchannel, micro liquid flow control method in the microchip.

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