JP4858909B2 - Microfluidic device with discharge mechanism and method for discharging a small amount of sample - Google Patents

Description

  The present invention relates to a microfluidic device including a mechanism for discharging a micro sample in a microchip and a method for discharging a micro sample in a microchip.

  In biotechnology, chemical application, and analysis, a micropipette having a disposable tip is generally used for weighing a small amount of sample and handling it after weighing. However, it is very difficult to weigh and handle a micro sample of microliter or less using a micropipette.

  So far, the measurement and handling of trace samples have been studied and put into practical use in the field of inkjet heads. For example, an inkjet head that uses a piezoelectric element as a drive source or bubbles generated by heating with an electric heater to discharge a minute sample as minute droplets and a driving method thereof are known (Patent Document 1).

  Microchips for electrophoresis, chemical reaction, and analysis use thin channels with a diameter of several to hundreds of microns, and water, various aqueous solutions, organic solvents, various chemicals, etc. Use the liquid.

  Although the control method in the microchip channel of the liquid existing in the thin channel of such a microchip is known (Patent Document 2), a specific part of the liquid in the microchip channel, Alternatively, it is very difficult to take out a specific substance analyzed / separated in the microchip channel out of the channel in a constant amount.

With regard to taking out samples from microchips, several types of microvalves have been developed, including 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 3). However, these are tip chips, complicated drive units integrated with microchips, or require external driving gas pressure, and the joints with the microchip occupy a large area, making the device large. There were problems such as difficulty in making chips disposable.
JP 2003-165222 A JP2005-300333 JP 2004-33919 A

  The present invention relates to a microfluidic device with a discharge mechanism having a microchip for electrophoresis, chemical reaction, analysis, etc., which is easier to measure and handle a small amount of sample and is suitable for miniaturization, and the microchip. It is an object to provide a method for taking out a sample from a microchannel.

  Under such circumstances, the present inventors can easily discharge the substance in the microchannel from the discharge port by applying a laser beam to the absorber provided on the inner wall of the microchannel in the microchip to generate bubbles. Found to get. The present inventors have further studied the combination of the chip, the light transmittance of the liquid, the light absorption rate of the absorber, the pulse width of the laser, the peak power, and the like, and as a result, the present invention has been completed.

  The present invention relates to the following microfluidic device with a discharge mechanism and a method for discharging a small amount of sample from a microchip.

  Item 1. In a microchip having at least one microchannel, at least one port capable of discharging a substance to the outside of the microchannel, and at least one absorber on the inner surface of the microchannel, the absorber is supplied from a laser generator. A method for discharging a small amount of sample, wherein a laser is absorbed to heat a liquid in a microchannel to generate bubbles, and a substance in the microchannel is discharged out of the microchannel.

Item 2. At least one microchannel in which a substance moves, at least one port capable of discharging the substance to the outside of the microchannel, a microchip including at least one absorber on the inner surface of the microchannel, and at least one laser generator A microfluidic device with a discharge mechanism comprising:
A micro with an ejection mechanism in which the absorber absorbs the laser from the laser generator and heats the liquid in the micro channel to generate bubbles, and the substance in the micro channel can be ejected outside the micro channel. Fluid device.

  Item 3. The microchip can discharge the substance to the outside of the first microchannel, the second microchannel separated from the first microchannel through the thin film, the first microchannel through which the substance moves, and the first microchannel And a bubble generating mechanism capable of forming bubbles on the inner wall of the second microchannel, and the first microchannel is pushed through the thin film by the generation of bubbles, Item 3. The microfluidic device with a discharge mechanism according to Item 2, which can be discharged out of the microchannel.

  Item 4. There are two or more combinations of the absorber and the port, the number of the laser generators is smaller than the number of the combination of the absorber and the port, and the laser beam scanning device, the chip moving device, or the laser beam scanning Item 4. The microchannel device with an ejection mechanism according to Item 2 or 3, further comprising a combination of an apparatus and a chip moving device, wherein the laser light scanning device, the chip moving device, or the laser light scanning device and the chip moving A microfluidic device with an ejection mechanism, wherein ejection is performed by switching a combination of an absorber to which a laser beam is irradiated and a port using a combination with an apparatus.

  Item 5. Item 5. The microfluidic device with a discharge mechanism according to any one of Items 2 to 4, wherein the microchip is a microchip for electrophoresis, chemical reaction, analysis, or micro sample amount control.

  Item 6. Item 6. The microfluidic device with a discharge mechanism according to any one of Items 2 to 5, wherein the microchip is a disposable microchip.

  Item 7. When the substance moves on the at least one microchannel and moves to the vicinity of the port, the absorber provided on the inner surface of the microchannel is irradiated with pulsed laser light to generate bubbles, and the port A method for discharging a small amount of sample from a microchip, wherein a substance present in the vicinity is discharged out of a flow path.

  Item 8. Item 8. The method according to Item 1 or Item 7, wherein the ejection amount is controlled by the number of irradiation times of the pulsed laser beam.

  By using the microfluidic device with a discharge mechanism of the present invention, it is possible to discharge a sample by an external operation without installing a drive system in the microchip, and it is possible to reduce the size.

  Furthermore, the microfluidic device with a discharge mechanism of the present invention is characterized in that the laser is visible or near infrared, and a small-sized laser such as a laser diode that can be stably operated for a long time can be used. Miniaturization and cost reduction are 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.

  In the present invention, the device provided in the microchip for discharging the substance is only the thin film absorber. Since the other devices are devices outside the microchip, the microchip in the microfluidic device with a discharge mechanism of the present invention is suitable for “disposable” and “multi-point drive” and can be used for a biochip or the like.

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

  The microfluidic device with a discharge mechanism of the present invention includes a microchip and a laser generator.

  The microchip included in the microfluidic device with a discharge mechanism of the present invention can be used for measuring, handling, and for electrophoresis, chemical reaction, analysis, and the like of a small amount of sample.

  The microchip has one or two or more microchannels intersecting each other.

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

  In one embodiment of the present invention, for example, in a microchip for electrophoresis, a voltage is applied by connecting electrodes to both ends of a microchannel, and a substance to be separated is distributed on the microchannel according to properties such as charge and molecular weight. Can move. 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 microchannel, for example, and a reaction product is obtained in the microchannel. When a plurality of reagents are present, the number of microchannels corresponding to the number of reagents can be formed, and a reaction product can be obtained at the intersection of the microchannels.

  The microchannel is 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, A solvent, an organic solvent, etc. are preferable. The liquid generates bubbles by heating.

  Although it will not specifically limit as an organic solvent if it has a clear boiling point, For example, alcohol, ether, etc. are mentioned.

  In the liquid here, biopolymers such as protein, DNA, RNA, sugar, glycoprotein, glycolipid, or fine particles made of metal, metal complex, ceramics, or the like may be dispersed.

  The width or diameter of the microchannel is about 1-1000 μm, preferably about 2-500 μm, more preferably about 5-400 μm.

  The microchip of the present invention may have bubble generating means that can generate bubbles on the inner surface of at least one microchannel. A desired substance such as the reaction product in the microchannel is pushed out of the microchip by a generated bubble through a discharge port (hereinafter also referred to as a discharge port).

  The absorber is a light absorber that absorbs laser light, and the absorption rate of the light absorber is about 0.1 to 0.99, preferably about 0.15 to 0.9.

  One absorber may be installed on the inner surface of the microchannel, or a plurality of absorbers may be installed.

  One discharge port may also be installed on the inner surface of the microchannel, or a plurality of discharge ports may be installed.

  The distance between the absorber and the discharge port is about 0 to 1000 microns, preferably about 0 to 500 microns, as the distance between both ends.

  By setting the distance between the absorber and the discharge port within the above range, the pressure generated by the generation of bubbles is sufficiently transmitted to the vicinity of the discharge port, and the substance can be discharged even with relatively small pulse energy.

  One absorber may be installed for each discharge port, two absorbers may be installed so as to sandwich the discharge port, or a plurality of absorbers may be installed so as to surround the discharge port.

  The discharge port diameter of the discharge port on the microchip surface side (hereinafter sometimes referred to as “surface-side discharge port diameter”) may vary depending on the type of liquid in the microchannel, but is usually about 1 μm to 500 μm, preferably about 5 μm to 100 μm. It is. The discharge port diameter of the discharge port on the side of the micro flow channel wall (hereinafter also referred to as flow channel side discharge port diameter) may vary depending on the type of liquid in the micro flow channel, but is usually about 1 μm to 500 μm, preferably It is about 5 μm to 100 μm.

  By changing the ejection orifice diameter within the above range, the size of the ejected droplets can be controlled.

  As the irradiation light, any light source having a wavelength of about 250 nm to 1200 nm can be used, visible light, ultraviolet light, infrared light or the like can be used, and laser light is preferably used.

  Laser light is preferable because the liquid in the microchannel can be heated in a narrow range of submicrometer to micrometer and bubbles can be generated quickly.

  The absorber may be provided at any position of the microchannel, and the absorber may be provided at the intersection of the plurality of microchannels or in the vicinity thereof. The absorber moves the substance existing in the vicinity by the pressure associated with the generation of bubbles, preferably discharged from the discharge port provided in the microchannel to the outside of the microchannel (for example, the collection container 7 side in FIG. 2). Can be made.

  The absorber is capable of heating the liquid in the microchannel to the extent that bubbles are formed, and is preferably capable of heating rapidly to the boiling point of the liquid or higher. If the liquid can be heated quickly, the substance present at or near the discharge port can be discharged quickly. The time for heating from the start of heating to the boiling point of the liquid or more is usually within 10 milliseconds, preferably from 10 nanoseconds to 1 millisecond, and more preferably from about 50 nanoseconds to 100 microseconds. It is preferable that the liquid in the microchannel can be quickly heated by the absorber because the discharge port and the substance in the vicinity thereof can be discharged without escaping.

  In a preferred embodiment of the present invention, the microchip includes a first microchannel through which the substance moves as a microchannel, and a second microchannel separated from the first microchannel via a thin film. ing. In this embodiment, as the bubble generating means, an absorber is provided in the periphery or the periphery of the second microchannel, preferably in a position in contact with the second microchannel, and the absorber is locally heated by heating the absorber. Generate bubbles in the vicinity of

  In a particularly preferred embodiment of the present invention, when the laser absorber installed near the wall surface of the microchannel is irradiated with a strong pulsed laser having a short peak of 1 millisecond or less, the temperature at the interface between the absorber and the liquid suddenly increases. Ascending and liquid evaporation occurs. The evaporation of the liquid hardly occurs unless the energy density per pulse of the laser is 0.01 J / cm 2 or more. On the other hand, when the energy density is 3 J / cm 2 or more, the absorber is evaporated and impurities may be generated. 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 light to be irradiated has a wavelength that transmits to a certain extent with respect to a liquid flow of 240 to 1200 nm. For example, 532 nm YAG double wave, visible to near infrared wavelength laser diode, 1060 to 170 nm YAG fundamental wave, Yb fiber laser, 248 nm KrF excimer laser, 308 nm XeCl excimer laser, 351 nm XeF excimer laser, etc. can do. 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 1 millisecond, more preferably 10 nanoseconds to 100 microseconds. 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, normal glass, plastic, or the like can be used as the microchip body. The microchip can be obtained by stacking two or more plate-like or film-like materials (microchip body) having grooves corresponding to the microchannels.

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

  In a preferred embodiment, the micro sample ejection 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, when a small amount of sample is discharged, an absorber is placed in at least one flow path and laser irradiation is performed, and the internal liquid temperature is instantaneously raised to the boiling point or higher (microsecond level or lower). And a part of the liquid in the flow channel can be discharged from the discharge port to the outside of the micro flow channel by the pressure of the generated gas. Further, although the energy density per single irradiation of the laser depends on the physical properties of the absorber to be used, it is preferably in the range of 0.01 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 the microfluidic device of the present invention, by setting the dimensions of the micro flow path, the type of liquid, and the diameter of the discharge port within the above ranges, the liquid surface of the discharge port portion is caused by the surface tension of the liquid in the absence of laser irradiation. Since the droplets are held, the droplets do not fall, and the liquid pushed out by the pressure of generating bubbles is ejected in a manner in which the ejection amount, speed, and the like are controlled during laser irradiation.

  In one particularly preferred embodiment of the present invention, the microchip is transparent to the laser, the absorber 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.

  In one embodiment of the present invention, the microfluidic device of the present invention has two or more combinations of absorbers and ports, and the number of laser generators is less than the number of combinations of absorbers and ports. May be. In this embodiment, the microfluidic device of the present invention further includes a laser light scanning device, a chip moving device, or a combination of a laser light scanning device and a chip moving device. Here, as the laser beam scanning device and the chip moving device, those usually used in the field to which the present invention belongs can be used. By using a laser beam scanning device, a chip moving device, or a combination of a laser beam scanning device and a chip moving device, the combination of the absorber and the port to which the laser beam is irradiated is switched, and liquid is discharged from each discharge port. It can be carried out.

  Hereinafter, the present invention will be described in detail with reference to examples.

Example 1 Sample Discharge from Microchip to Sample Collection Container The microchip for electrophoresis of this example separates, discharges and collects a part of a sample from the microchip. As shown in FIG. 1, in the electrophoresis microchip 1, the sample is introduced into the microchannel 5 near the electrode hole 3, and flows along the channel 5 while flowing through the channel 5 toward the electrode hole 4. Sample mass distribution. The electrode holes 3 and 4 and the flow path 5 are filled with liquid such as water, saline or various buffer solutions.

  In this embodiment, the discharge port 6 is provided in the middle of the flow path 5. Laser light 11 output from the laser oscillator 10 at an appropriate timing, positioned and converged by the scanning device 9 and the lens 8 is irradiated to the laser absorber 7, and the liquid around the laser absorber 7 evaporates to form bubbles 13. Arise. By the pressure at this time, the liquid in the vicinity of the discharge port 6 moves and is discharged from the discharge port to the outside of the flow path 5, whereby only the discharge sample 15 can be guided to the sample collection container 12.

  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. In order to obtain a rise in pressure sufficient for ejection, it is desirable to irradiate the laser light by scanning with pulses or continuous light, and the single irradiation time by pulse width or scanning is preferably about 100 microseconds or less.

  It has been found that suitable laser energy density for sufficient evaporation to occur is in the range of 0.01 J / cm 2 to 3 J / cm 2, although it is material and pulse width dependent. The laser output is determined in consideration of the viscosity of the liquid used within this range.

Example 2 Sample discharge from microchips having various flow path patterns Laser light was irradiated using microchips having various flow path patterns shown in FIGS. 2b, 3a, 3b, 3c, and 3d.

  Specifically, a PMMA chip having a microchannel having a width of about 120 μm / 50 μm (channel surface width / bottom surface width), a depth of about 30 μm was formed by injection molding. A metal foil (135 μm × 135 μm × 2 μm) was installed as the laser absorber 7 at the position shown in each figure. An acrylic (PMMA) film having a thickness of about 40 μm (including the thickness of the adhesive material) was used as the seal film 2. A discharge port 6 is formed on the seal film 2 by fs laser irradiation.

Each microchip was filled with a commercial red ink diluted with water as a sample, and the absorber was irradiated with a laser beam having a wavelength of 1070 nm so as to obtain a laser energy density of 0.6 to 2.5 J / cm ² .

  In any flow path pattern, the discharge of the sample was confirmed.

Example 3 Mass Spectrometry Data Before and After Sample Discharge Using the microchip having the flow path pattern shown in FIG.

  A microchip having a microchannel having a width of about 120 μm / 50 μm (channel surface width / bottom surface width) and a depth of about 30 μm and provided with metal foil (135 μm × 135 μm × 2 μm) was used. The seal film 2 having a thickness of about 50 μm was used. The seal film 2 is provided with a discharge port 6 having a surface discharge port diameter / flow channel side discharge port diameter of 44/30 (micron / micron) by fs laser irradiation.

  The microchip was filled with a protein sample (cytochrome c: 0.1 mg / water 1 ml, 1 mg / water 1 ml, BSA: 0.1 mg / water 1 ml, 1 mg / water 1 ml). The absorber 7 was heated using a single mode fiber laser with an output of 40 W CW and a wavelength of 1060 nm, and the protein sample was discharged onto a protein chip array for SELDI-TOF MS.

  The SELDI-TOF MS signal of the BSA sample before and after ejection is shown in FIGS. 4a and 4b. The SELDI-TOF MS signals of cytochrome c samples before and after discharge are shown in FIGS. 4c and 4d. As apparent from FIGS. 4a and 4b, the signal intensity was not proportional to the sample concentration. However, with regard to the peak position, there is no significant difference between the signal of the post-discharge BSA sample and the signal of the pre-discharge BSA sample. I couldn't see it. As is clear from FIGS. 4c and 4d, similar results were obtained for cytochrome c.

  From these results, it can be seen that by using the microfluidic device with a discharge mechanism of the present invention, the sample can be discharged from the microchip without decomposing and denaturing the protein by laser irradiation.

Example 4 Relationship between the number of discharges and the discharge amount As a protein sample, a BSA sample (0.1 mg / 1 ml of water) was used, and in the same manner as in Example 3, a sample was removed from a microchip by laser irradiation, and a protein chip for SELDI-TOF MS Approximately 600 discharges were made to the array.

  The signal of the discharged sample was detected using SELDI-TOF MS, and the discharge amount was evaluated from the detection signal. FIG. 5 shows detection signals at the time of each ejection (injection).

  As apparent from FIG. 5, the signal level changes in proportion to the number of ejections. Therefore, by using the microfluidic device with a discharge mechanism of the present invention, the discharge amount can be controlled by the number of discharges (or the number of times of laser light irradiation), and a minute sample can be measured and handled as a nano-pico pipette. is there.

Example 5 Relationship between Laser Energy and Discharge Rate for Each Discharge Port Size Discharge ports with surface discharge port diameter / flow path side discharge port diameters of 31/13, 35/22, 44/30, and 54/36 (microns / micron) Using the microchip having the flow path pattern shown in FIG. 2b, a sample was discharged from the microchip by laser light irradiation in the same manner as in Example 3. The injection rate was calculated from the amount of the discharged sample.

  Here, the injection rate indicates the number of ejections / the number of laser irradiations.

  FIG. 6 shows the injection rate at each pulse energy when a microchip having a discharge port with a surface discharge port diameter / flow path side discharge port diameter of 35/22 (micron / micron) is used.

  As apparent from FIG. 6, the injection rate is almost 100% in the range of 70 to 190 microjoules, and there is almost no variation in the injection rate.

  The data shown in FIG. 6 is the injection rate at the start of discharge, but once discharge occurred, the injection rate was almost 100% in the range of 50 to 200 microjoules (data not shown).

  In addition, when a microchip having discharge ports of surface discharge port diameter / flow channel side discharge port diameters of 31/13, 44/30, and 54/36 (micron / micron) is used, the injection rate is almost 100% as described above. (Data not shown).

Example 6 The flow path pattern shown in FIG. 2a having a discharge surface with a drive surface discharge port diameter / flow channel side discharge port diameter of 35/22 (microns / micron) of a plurality of discharge mechanisms by a single laser device is formed on one microchip. The three ejection mechanisms were driven by a single laser device by moving the chip. There was no change in the discharge conditions due to the addition of the moving mechanism, and it was confirmed that multiple points were switched.

Example 7 Speed Control of Ejected Droplets Droplets were ejected from the microfluidic device under the conditions shown in FIG. 7, and the ejected droplets were photographed using a CCD. This operation was performed by laser irradiation with laser energy of 70 μJ and 170 μJ. FIG. 8 shows the photograph taken and the relationship between the delay time from laser irradiation and the distance from the chip to the droplet at each time point.

  The droplet velocity was about 3.2 m / s at a laser energy of 70 μJ and about 5.0 m / s at 170 μJ. From this, it can be seen that the velocity of the ejected droplets can be controlled by changing the laser energy.

  The higher the droplet velocity, the more the droplet can be linearly moved farther, and by lowering the droplet velocity, the force that the molecules in the droplet receive during ejection and landing is reduced, making the molecule more susceptible to breakage. Yes. Therefore, the method of the present invention has the advantage that the droplet velocity can be controlled to a velocity depending on the application by adjusting the laser energy.

FIG. 1a is an overall view showing the concept of a microfluidic device with a discharge mechanism according to an embodiment of the present invention. FIG. 1b is an enlarged view of the main part of FIG. 1a. FIG. 2a is an enlarged view of a main part of FIG. 1a. 2b is a cross-sectional view taken along line A-A 'of FIG. 2a. 3a, 3b, 3c, and 3d are cross-sectional views showing modifications of the microfluidic device with a discharge mechanism according to the embodiment of the present invention. 4a and 4b show the SELDI-TOF MS signal of the BSA sample before (FIG. 4a) and after (FIG. 4b) ejection from the microchip. 4c and 4d show SELDI-TOF MS signals of cytochrome c samples before (FIG. 4c) and after (FIG. 4d) ejection from the microchip. FIG. 5 shows the SELDI-TOF MS signal of the BSA sample when the sample is ejected at various times from the microchip. FIG. 6 shows sample ejection rates when laser light is irradiated with various pulse energies. FIG. 7 shows a schematic diagram of a microfluidic device according to an embodiment of the present invention and an apparatus for photographing ejected droplets, and a photograph of the photographed droplets. FIG. 8 is a stroboscopic photograph of a droplet ejected from the microfluidic device of the present invention, and a graph showing the relationship between the delay time from laser irradiation and the distance from the microchip at each time point.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Microchip 2 Seal film 3 Electrode hole 4 Electrode hole 5 Micro flow path 6 Discharge port 7 Laser absorber 8 Condensing lens 9 Laser scanning apparatus 10 Laser oscillator 11 Laser light 12 Sample collection container 13 Bubble 14 Pressure 15 Discharge sample

Claims (8)

At least one microchannel, at least one port capable of discharging a substance to the outside of the microchannel, and at least one absorber on the inner surface of the microchannel, the microchip includes an upstream end to a downstream end of the microchannel. In the state where the liquid is flown and there is no laser irradiation, the liquid droplet does not fall from the port, the absorber absorbs the laser from the laser generator, and the liquid in the micro flow path is heated to generate bubbles, and the micro A method for discharging a small amount of sample, characterized in that a substance in a flow path is discharged from the port to the outside of the micro flow path,
The port and the absorber are located on the same microchannel, and the port is located upstream of the absorber;
Method. A microchip having at least one microchannel in which a substance moves from the upstream end to the downstream end, at least one port capable of discharging the substance to the outside of the microchannel, and at least one absorber on the inner surface of the microchannel ; A microfluidic device with a discharge mechanism comprising at least one laser generator and means for moving a substance in the microchannel, wherein the port and the absorber are located on the same microchannel; and When the port is located upstream of the absorber and there is no laser irradiation , the liquid droplet does not fall from the port, and the absorber absorbs the laser from the laser generator and absorbs the liquid in the microchannel. A microfluidic device with a discharge mechanism capable of generating bubbles by heating and discharging a substance in the microchannel from the port to the outside of the microchannel. A microchip having at least one microchannel in which a substance moves from the upstream end to the downstream end, at least one port capable of discharging the substance to the outside of the microchannel, and at least one absorber on the inner surface of the microchannel ; A microfluidic device with a discharge mechanism comprising at least one laser generator and a means for moving a substance in the microchannel , wherein the liquid droplets do not fall from the port in the absence of laser irradiation, and the absorption A microfluidic device with an ejection mechanism, in which the body absorbs the laser from the laser generator and heats the liquid in the microchannel to generate bubbles and ejects the substance in the microchannel out of the microchannel And
The microchip can discharge the substance to the outside of the first microchannel, the second microchannel separated from the first microchannel through the thin film, the first microchannel through which the substance moves, and the first microchannel And a bubble generating mechanism capable of forming bubbles is installed on the inner wall of the second micro-channel, and the first micro-channel is located downstream of the port through the thin film due to the generation of bubbles. A microfluidic device with a discharge mechanism that can push a substance inside and discharge it from the port to the outside of the first microchannel. There are two or more combinations of the absorber and the port, the number of the laser generators is smaller than the number of the combination of the absorber and the port, and the laser beam scanning device, the chip moving device, or the laser beam scanning 4. The micro-channel device with an ejection mechanism according to claim 2, further comprising a combination of an apparatus and a chip moving device, wherein the laser light scanning device, the chip moving device, or the laser light scanning device; A microfluidic device with an ejection mechanism, which performs ejection by switching a combination of an absorber to which a laser beam is irradiated and a port using a combination with a chip moving device. The microfluidic device with a discharge mechanism according to any one of claims 2 to 4, wherein the microchip is a microchip for electrophoresis, chemical reaction, analysis, or micro sample amount control. The microfluidic device with a discharge mechanism according to any one of claims 2 to 5, wherein the microchip is a disposable microchip. When the substance moves on the at least one microchannel from the upstream end to the downstream end and moves to the vicinity of the port, a bubble laser beam is irradiated to the absorber provided on the inner surface of the microchannel. And discharging a substance present in the vicinity of the port to the outside of the flow path , wherein a droplet is dropped from the port in the absence of laser irradiation. First, the port and the absorber are located on the same microchannel, and the port is located upstream of the absorber. The method according to claim 1 or 7, wherein the ejection amount is controlled by the number of times of irradiation of the pulsed laser beam.

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