The nature of this invention, as well as other objects and advantages thereof, will be explained in the following with reference to the accompanying drawings, in which like reference characters designate the same or similar parts throughout the figures and wherein:
As shown in
The micro channel 12 formed in the main body 18 has the coalescence portion 14 composed of a Y-shaped channel formed on an upstream side in a transport direction of the droplets A and B, and also has the diverging portion 16 formed with a branch channel on a downstream side. The coalescence portion 14 is rendered as the Y-shaped channel since the present embodiment is described by taking an example of coalescing two droplets A and B of different compositions into one coalesced droplet C in the coalescence portion 14. However, the shape of the coalescence portion 14 is not limited to the Y-shaped channel, and it is possible that the coalescence portion 14 is composed of the number of channels necessary for the number of the droplets to be coalesced.
Two ends of the Y-shaped channel penetrate through to a top face 18A of the main body 18 via their respective through-holes 14A, to which the droplet injection device 20 and the transfer device 22 are connected. More specifically, ends of injection tubes 24 are detachably connected to the through-holes 14A. The droplets A and B are injected into the injection tubes 24 from the other ends of the injection tubes 24 by using syringes 26, only one of which is shown in
As for the syringes 26, syringes of a micro capacity may be suitably used for instance. As for the air supply instruments 30, micropumps capable of supplying gas of a micro amount can be suitably used.
The diverging portion 16 configures an inverted T-shaped channel in
The reciprocation device 25 is connected to the upper end of the branch channel 12B. More specifically, an end of piping 32 is detachably connected to the upper end of the branch channel 12B, and a reciprocation instrument 34 is connected to the other end of the piping 32. As for the reciprocation instrument 34, it is possible to suitably use a pressurization/suction micropump which can alternately pressurize and suction the branch channel 12B. As described above, it is possible to render only the main body 18 disposable by rendering the injection tubes 24 and the piping 32 detachable from the main body 18.
It is possible that the branch channel 12B composing the diverging portion 16 has an even channel diameter as in
As shown in
It is preferable that the channel section in equivalent diameter of the micro channel 12 is in the range of 50 μm through 2 mm, more preferably the range of 100 μm through 1 mm. Here, the equivalent diameter is the diameter in the case where the channel section is regarded as a circle. It is preferable that the inner wall of the micro channel 12 has the wettability so that the contact angle of the droplets A and B to the inner wall of the micro channel 12 is in the range of 20° to 180°, more preferably the range of 60° to 180°. That is because the lower the wettability of the droplets A and B to the inner wall of the micro channel 12 is, the more dynamic change of the shape of the coalesced droplet C due to the reciprocation in the diverging portion 16 is apt to occur, and the mixing is thereby promoted.
The main body 18 can be manufactured by utilizing high-precision processing technology, such as micro drill processing, micro-discharge processing, molding utilizing plating, injection molding, dry etching, wet etching and hot embossing. Machining techniques using a lathe and a drilling machine of general-purpose may also be utilized.
Material of the main body 18 is not especially limited but may be a material to which the above-mentioned processing technology is applicable. More specifically, there are suitably usable materials, such as metallic materials (iron, aluminum, stainless steel, titanium, or other various metals), resin materials (acrylic resin, polydimethylsiloxane (PDMS), and the like), glass (silicon, heat-resistant and chemical-resistant glass, silica glass, and the like), heat-resistant and chemical-resistant glass or silica glass having undergone a parylene treatment (paraxylene deposition) or having undergone a silane coupling treatment of a fluorine system or a hydrocarbon system.
As will be described in the droplet mixing method later, it is desirable to manufacture the main body 18 with a transparent material so as to allow visual observation of a coalescence state of the two kinds of droplets A and B and the reciprocation state of the coalesced droplet C in the diverging portion 16.
It is also desirable to provide a heating device (not shown) for heating the main body 18. As for the heating device, there are methods, such as elaborating a heater structure of a metallic resistance wire, polysilicon and the like in the main body 18. In the case of the heater structure of a metallic resistance wire, polysilicon and the like, temperature is controlled by using the heating device as to heating and performing a thermal cycle by natural cooling as to cooling. As for measurement of the temperature in this case, there is a generally adopted method wherein another same resistance wire is elaborated and temperature measurement is performed according to change of the resistance thereof in the case of the metallic resistance wire, and the temperature measurement is performed by using a thermocouple in the case of the polysilicon. In recent years, temperature control of blood can be accurately performed by incorporating a temperature control function using a Peltier element into the main body 18. At any rate, the temperature control itself is possible either by a conventional temperature control technique or by a new temperature control technique represented by the Peltier element. Therefore, an optimal method can be selected by combining selection of a heating/cooling mechanism and a temperature measurement mechanism according to the material and the like of the main body 18 with the configuration of an external control system.
Next, the droplet mixing method of the present embodiment is described with reference to the droplet mixing apparatus 10 configured as above.
First, as shown in
Next, the air supply instruments 30 are driven to supply the air pipes 28 with gas (air for instance), and the droplets A and B injected in the injection tubes 24 are transferred to the coalescence portion 14 of the micro channel 12. Thereby, as shown in
Next, at least one of the air supply instruments 30 is continuously driven and the coalesced droplet C is transferred to the diverging portion 16, and then the driving of the at least one of the air supply instruments 30 is stopped.
Next, the reciprocation instrument 34 is driven to repeat pressurization and depressurization (suction) on the branch channel 12B constituting the diverging portion 16. The coalesced droplet C is thereby reciprocated in the diverging portion 16 while changing its moving direction so as to mutually mix the droplets A and B by generating an asymmetrical flow within the coalesced droplet C. As for a reciprocation frequency of the coalesced droplet C, that is, a pressurization and depressurization cycle of the reciprocation instrument 34, it is preferable that the reciprocation frequency is in the range of 0.1 Hz through 5 Hz, more preferably the range of 0.1 Hz through 2 Hz. It is preferable that the gas amounts sent from and suctioned by the reciprocation instrument 34 for reciprocating the coalesced droplet C is in the range of 0.1 μL/minute through 1000 μL/minute.
Thus, as shown in
If the coalesced droplet C is broken in the reciprocation of the coalesced droplet C, the droplets A and B separately reciprocate in the diverging portion 16 so that mixing performance deteriorates. Moreover, if the coalesced droplet C is broken and there are the droplets A and B left, droplet diameters become smaller so that dynamic shape deformation of the droplets is no longer performed in the diverging portion 16. Therefore, it is necessary to perform the reciprocation so as not to break the coalesced droplet C. For that purpose, it is important to adequately set the number of times of the reciprocation and a distance for performing the reciprocation. Although the number of times of the reciprocation necessary for the mixing depends on physicality of liquids to be used, it has been verified that only one or two reciprocations can render the liquids homogenized, in the case where both the liquids are aqueous solutions of low solute density.
Thus, the droplet mixing method of the present embodiment coalesces the droplets A and B for the mixing to form the coalesced droplet C, and reciprocates the coalesced droplet C in the diverging portion 16. It is thereby possible to mutually mix the droplets in the micro channel 12 with high efficiency.
As shown in
The droplet mixing apparatus 40 of the second embodiment is different from the first embodiment in that it only provides the diverging portion 16 in the micro channel 12 without providing the coalescence portion 14, configures the injection tube 24 and the air pipe 28 as single pieces, and newly provides the fixing device (not shown) which fixes the fixed object D in the diverging portion 16 of the micro channel 12. The droplet mixing apparatus 40 of the second embodiment is the same as the first embodiment as to the droplet injection device 20, the transfer device 22, the reciprocation device 25, the diameter of the micro channel 12, the contact angle of the droplet A to the inner wall of the micro channel 12, the reciprocation frequency of the droplet A in the diverging portion 16 and manufacturing method of the main body 18. Hence, descriptions thereof are omitted here. It is preferable in the second embodiment also to have the restrictor 12C and make the branch channel 12B oblique in the diverging portion 16.
As for the fixing device which fixes the fixed object D in the diverging portion 16, an inkjet apparatus can be utilized for instance. More specifically, a jet nozzle is mounted at the end of the branch channel 12B at the diverging portion 16, and a liquid including the fixed object D is deposited on the bottom of the diverging portion 16 from the jet nozzle so as to fix the fixed object D on the bottom of the diverging portion 16.
According to the droplet mixing method using the droplet mixing apparatus 40 of the second embodiment configured as above, the fixed object D is fixed on the diverging portion 16 as shown in
Therefore, if blood is used as the droplet A and an antibody is fixed as the fixed object D in the diverging portion 16, a simplified blood test by an antibody-antigen reaction can be performed with a simple instrument.
It is also possible that the droplet mixing apparatus of the first embodiment having the coalescence portion 14 is adapted to fix the fixed object D to the diverging portion 16 with the fixing device, and to reciprocate the coalesced droplet C, to which the multiple kinds of droplets are coalesced in the coalescence portion 14, in the diverging portion 16. If the droplet mixing apparatus is thus configured, it is possible to coalesce and make react the droplet A of blood with a droplet of developing solution in the coalescence portion 14 first and then efficiently contact the reacted coalesced droplet C with an antibody (fixed object) in the diverging portion 16. Thus, the range of applications is expanded.
According to the first and second embodiments of the present invention, the droplets A and B injected into the injection tubes 24 and 24 are transferred by the gas pressure of the transfer device; however, it is also possible to use the liquid other than the gas. The liquid in this case needs to be the liquid that neither mixes nor reacts with the droplets A and B and the fixed object D. In the case of using the liquid, an outlet tube is connected to the air vent port 38 so that the liquid is discharged to an adequate place through the outlet tube when transferring the droplets.
Next, a description is given as to a comparative testing for comparing the mixing performance between the droplet mixing apparatus 10 according to the embodiment of the present invention shown in
In a first example of the present invention, the droplet mixing apparatus 10 including the diverging portion 16 having the restrictor 12C formed in the connection portion of the branch channel 12B as shown in
In a second example of the present invention, the droplet mixing apparatus 10 including the diverging portion 16 having the branch channel 12B oblique to the main channel 12A by 45° in addition to have the restrictor 12C as shown in
In a comparative example, the conventional droplet mixing apparatus including a mixing portion having a mere linear channel on the downstream side of a confluent portion as shown in
As for the channel diameters of the diverging portions of the first and second examples and the linear channel portion of the comparative example, they had common channel width and depth of 0.2 mm each. The diameter of the restrictor 12C of the diverging portion 16 was 0.15 mm. The branch channel 12B of the diverging portion 16 was formed at a position of 5 mm downstream from the coalescence portion 14. In the first and second examples and the comparative example, the main body was made of a transparent acrylic resin so as to visually observe the droplet in the micro channel 12.
In the first example, the droplet A (150 nL) of a red aqueous dye and the droplet B (150 nL) of a yellow aqueous dye were injected into the micro channel including the diverging portion 16 having the restrictor 12C and coalesced to the coalesced droplet C (300 nL) in the coalescence portion 14, and then the coalesced droplet C was reciprocated and mixed in the diverging portion 16. A syringe pump was used as the reciprocation instrument for performing the reciprocation of the coalesced droplet C.
The second example was the same as the first example except that it reciprocated and mixed the coalesced droplet C in the diverging portion 16 having the branch channel 12B oblique to the main channel 12A by 45° in addition to have the restrictor 12C.
In the comparative example, the droplet A of the red aqueous dye and the droplet B of the yellow aqueous dye were injected into the micro channel and coalesced to the coalesced droplet C in the coalescence portion 14, and then the coalesced droplet C was reciprocated and mixed in the linear channel portion. A distance between the confluent portion and the linear channel portion in the comparative example was the same as the distance between the confluent portion and the diverging portion of the first and second examples; in other words, the coalesced droplet C was reciprocated in the position equivalent to the position where the diverging portion was.
In the first and second examples and the comparative example, the coalesced droplet C was reciprocated at the frequency (cycle period of pressurization and suction) of 0.5 Hz. The gas amount for pressurization and suction was 5 μL/minute.
In each example, the coalesced droplet C was observed though a CCD mounted on an erecting microscope, and it was timed until there was no uneven luminance in the image of the coalesced droplet C. The time until there was no uneven luminance was regarded as mixing time. Evaluation was performed so that, the shorter the mixing time became, the better the mixing performance was. An objective lens of the erecting microscope had a magnification of 10.
It took 4 seconds in the comparative example until the uneven luminance of the coalesced droplet C sufficiently disappeared, while it took 3 seconds in the first example and 2 seconds in the second example until there was no uneven luminance. Although these examples showed mutual mixing of the droplets, it was sufficiently presumable from these results that chaotic flows were generated by friction with the channel wall. Therefore, even in the case of the droplet and the fixed object fixed on the channel wall of the diverging portion, the droplet can contact the fixed object with high efficiency.
Thus, it is possible, by using the droplet mixing apparatus of the present invention, to contact and mix the droplets mutually or the droplet with the fixed object, in the micro channel with high efficiency.
It should be understood, however, that there is no intention to limit the invention to the specific forms disclosed, but on the contrary, the invention is to cover all modifications, alternate constructions and equivalents falling within the spirit and scope of the invention as expressed in the appended claims.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2006-269530 | Sep 2006 | JP | national |