JP2007224844A - Micropump, liquid feeding method and liquid feeding system - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a liquid feeding method and a liquid feeding system capable of increasing liquid feeding speed at a time of liquid feed in a main direction in an embodiment in such a case that liquid to be used for reaction is fed to a downstream in a channel of a micro-reactor, and simultaneously capable of sufficiently preventing formation of bubbles in a pump chamber in a case that liquid is fed in any directions in a micropump capable of feeding liquid in both directions with using change ratio of channel resistance to change of pressure difference. <P>SOLUTION: For an oscillating actuator connected to a pressurizing chamber to which a first channel and a second channel of which change rate of channel resistance to change of pressure difference is smaller than that of the fist channel, voltage rise time T1 of first drive voltage wave form for feeding liquid in a direction toward the second channel from the first channel is set shorter than voltage rise time T7 of a second drive voltage wave form for feeding liquid in a direction toward the first channel from the second channel. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a liquid feeding method and a liquid feeding system using a micropump. More specifically, the internal pressure of a pressurizing chamber to which flow rates having different flow rate change ratios with respect to a change in differential pressure are connected is changed. The present invention relates to a liquid feeding method and a liquid feeding system of a micropump for feeding liquid in both directions by a voltage waveform applied to an actuator connected to a pressurizing chamber. In particular, the present invention relates to an improvement in technology for sending a liquid used for a reaction by a driving liquid from a micropump in a flow path of a microreactor.

In recent years, by making full use of micromachine technology and ultrafine processing technology, devices and means (for example, pumps, valves, flow paths, sensors, etc.) for performing conventional sample preparation, chemical analysis, chemical synthesis, etc. have been miniaturized. Systems integrated on a chip have been developed. this is,
It is also called μ-TAS (Micro total Analysis System), bioreactor, Lab-on-chips, biochip, and its application is expected in medical examination / diagnosis field, environmental measurement field, agricultural production field Has been. As can be seen in the current genetic testing, when complicated processes, skilled techniques, and equipment operations are required, automated, accelerated and simplified microanalysis systems are costly and require samples. The benefit is great in that it allows analysis not only in quantity and time, but also in any time and place.

  In various types of analysis and inspection, importance is attached to the quantitativeness of analysis, the accuracy of analysis, and the economic efficiency of these analysis chips. For this purpose, it is a challenge to establish a highly reliable liquid delivery system with a simple configuration, and there is a need for a microfluidic control element that is highly accurate and highly reliable. One is disclosed in Patent Document 1.

  This micro pump is capable of two-way liquid feeding depending on the voltage waveform applied to the actuator, and has a structure in which flow paths having different flow rate resistance change ratios with respect to differential pressure changes are connected to a pressurizing chamber. Yes. A diaphragm is formed on the wall surface of the pressurizing chamber, and an actuator composed of a piezoelectric element or the like is connected to the outer surface of the diaphragm. The pressurizing chamber communicates with the first flow path in which the flow path resistance changes according to the differential pressure and the second flow path in which the change rate of the flow path resistance with respect to the change in the differential pressure is smaller than that of the first flow path. ing.

  When the voltage having the waveform shown in FIG. 5A is applied to the actuator, the diaphragm is quickly displaced in the direction toward the inside of the pressurizing chamber in the period T1 during which the voltage suddenly rises, and the first flow path and the second flow path are changed. The volume of the pressurizing chamber decreases while a large differential pressure is applied to the flow path.

  Next, in period T2, the voltage is maintained at a constant value e1, and then in period T3 in which the voltage gradually falls, the diaphragm is slowly displaced in the direction from the pressurizing chamber toward the outside thereof, and the first flow path and the second flow path. The volume of the pressurizing chamber increases while a small differential pressure is applied to the flow path.

By applying the trapezoidal voltage waveform repeatedly at intervals of the period T4, the liquid is fed in one direction.
When the liquid is fed in the opposite direction, the voltage waveform of FIG. 5B having a shape obtained by inverting the waveform of FIG. 5A is used for convenience of voltage control and the like. When the voltage having the waveform shown in FIG. 5B is applied to the actuator, the diaphragm is slowly displaced in the direction toward the inside of the pressurizing chamber in the period T5 during which the voltage gradually rises. The volume of the pressurizing chamber decreases while a small differential pressure is applied to the flow path.

  Next, in period T6, the voltage is maintained at a constant value e1, and then in period T7 in which the voltage falls steeply, the diaphragm is quickly displaced in the direction from the pressurizing chamber to the outside thereof, and the first flow path and the second flow path The volume of the pressurizing chamber increases while a large differential pressure is applied to the flow path.

By repeatedly applying the trapezoidal voltage waveform at intervals of the period T8, the liquid is fed in the opposite direction.
By connecting the micropump to the upstream side of the microreactor channel and sending the driving liquid to the microreactor channel, the liquid used in the reaction in the microreactor channel can be pushed and fed.

Further, for example, when the reaction proceeds in the reaction part in the microreactor while shaking the reagent back and forth, the voltage waveform of FIG. 5A and the voltage waveform of FIG. By applying, the operation can be performed while switching the liquid feeding direction of the reaction liquid connected in series with the driving liquid a plurality of times in the forward and reverse directions.
JP 2001-322099 A

  When it is necessary to further increase the liquid feeding speed by the micropump, the speed can be increased by shortening the rising period T1 in the voltage waveform of FIG. The same applies to the case where the falling period T7 in the voltage waveform of FIG.

  However, when the liquid feeding speed is increased in this way, the following problem occurs. That is, compared with the case where liquid is fed in the direction from the first flow path to the second flow path with the waveform of FIG. 5A, the waveform of FIG. 5B is directed from the second flow path to the first flow path. When the liquid is fed in the direction, the negative pressure generated in the pressurizing chamber of the micropump increases with the vibration of the actuator.

For this reason, bubbles due to cavitation are easily generated in the pump chamber, which is a factor that hinders normal liquid feeding.
The present invention relates to a micropump capable of bidirectional liquid feeding utilizing a change rate of flow path resistance with respect to a change in differential pressure. Liquid feeding method and liquid feeding system capable of speeding up the liquid feeding speed at the time of liquid feeding in the main direction and at the same time sufficiently preventing generation of bubbles in the pump chamber regardless of the direction of liquid feeding. The purpose is to provide.

The liquid feeding method using the micropump of the present invention includes a first flow path in which the flow path resistance changes according to the differential pressure,
A second flow path whose rate of change in flow path resistance with respect to a change in differential pressure is smaller than the first flow path;
A pressurization chamber connected to the first flow path and the second flow path;
An actuator for changing the internal pressure of the pressurizing chamber;
A method of sending liquid in both directions using a micropump equipped with
The actuator is driven by a first drive voltage waveform in which a substantially trapezoidal voltage waveform is repeated, and liquid is fed in the direction from the first flow path to the second flow path,
The actuator is driven by a second drive voltage waveform in which a substantially trapezoidal voltage waveform is repeated, and liquid is fed in the direction from the second flow path to the first flow path,
The voltage rise time in the first drive voltage waveform is shorter than the voltage fall time in the second drive voltage waveform.

In the above invention, the driving fluid injection section provided upstream of the flow path of the microreactor to which the liquid used for the reaction in the flow path in the plate-shaped chip is communicated with the second flow path side of the micropump,
The actuator is driven by the first driving voltage waveform, the driving liquid is sent in the direction from the first flow path to the second flow path, and the driving liquid injected from the driving liquid injection portion into the flow path of the microreactor. The liquid used for the reaction is preferably pushed downstream and fed.

  In the above invention, the actuator is driven by the second driving voltage waveform, the driving liquid is fed in the direction from the second flow path toward the first flow path, and used for the reaction connected in series with the driving liquid. It is preferable that the liquid is fed to the driving liquid injecting portion in the direction opposite to the downstream side.

The liquid feeding system using the micropump of the present invention is:
(I) a first flow path in which the flow path resistance changes according to the differential pressure;
A second flow path whose rate of change in flow path resistance with respect to a change in differential pressure is smaller than the first flow path;
A pressurization chamber connected to the first flow path and the second flow path;
An actuator for changing the internal pressure of the pressurizing chamber;
A micropump that can feed liquids with
(Ii) means for generating a first drive voltage waveform and a second drive voltage waveform in which a substantially trapezoidal voltage waveform for driving the actuator is repeated;
With
The voltage rise time in the first drive voltage waveform is shorter than the voltage fall time in the second drive voltage waveform,
The actuator is driven by the first drive voltage waveform to send liquid in the direction from the first flow path to the second flow path,
The actuator is driven by the second drive voltage waveform, and the liquid is fed in the direction from the second flow path to the first flow path.

In the above invention, the liquid feeding system includes a microreactor in which a liquid used for the reaction is stored in advance in a flow path in the plate-shaped chip and a reaction using a reagent is performed in the flow path.
In the upstream of the flow path of the microreactor, a driving liquid injecting unit for injecting a driving liquid for sending the liquid used for the reaction is provided,
A driving liquid injection part of the microreactor communicates with the second flow path side of the micropump,
The actuator is driven by the first driving voltage waveform to send the driving liquid in the direction from the first flow path to the second flow path, and by the driving liquid injected from the driving liquid injection portion into the flow path of the microreactor. It is preferable to send the liquid used for the reaction by pushing it downstream.

  In the above invention, the actuator is driven by the second driving voltage waveform, the driving liquid is fed in the direction from the second flow path toward the first flow path, and used for the reaction connected in series with the driving liquid. It is preferable that the liquid is fed to the driving liquid injecting portion in the direction opposite to the downstream side.

  According to the above-described invention, the flow path, for example, the microreactor, in which the liquid to be fed by the driving liquid is located downstream of the second flow path where the change rate of the flow path resistance with respect to the change in the differential pressure is smaller than the first flow path The direction from the first flow path to the second flow path is the main direction of liquid feed, and the first drive voltage waveform for liquid feed in this direction and the liquid feed to the opposite side The second drive voltage waveform for this is asymmetrical. Specifically, the voltage rise time in the first drive voltage waveform is shorter than the voltage fall time in the second drive voltage waveform.

Therefore, even if the voltage value at the time of liquid feeding in one direction is the same as that at the time of liquid feeding in the other direction, the liquid feeding speed in the main direction can be increased, and at the same time, bubbles are likely to be generated in the pump chamber due to cavitation. The generation of bubbles is also suppressed during liquid feeding from the second flow path to the first flow path. Although the liquid feeding speed from the second flow path opposite to the main direction to the first flow path is slower than the liquid feeding speed in the main direction, it is practically used from the viewpoint of the application and use frequency of the reverse direction liquid feeding. The impact of is small.

  According to the present invention, it is possible to increase the liquid feeding speed at the time of liquid feeding in the main direction, and at the same time, it is possible to sufficiently prevent the generation of bubbles in the pump chamber regardless of the direction of liquid feeding.

  Embodiments of the present invention will be described below with reference to the drawings. 1 is a cross-sectional view of a micropump unit used in one embodiment of the present invention, FIG. 2 is a perspective view thereof, and FIGS. 3A and 3B are main directions (direction A) by the micropump. ) And a drive voltage waveform and a liquid delivery amount at the time of liquid feeding in the reverse direction (B direction). FIG. 4 is a diagram showing a microreactor that performs liquid feeding using this micropump unit.

  The microreactor used in this example performs a gene amplification reaction and detection of a reagent previously stored in the microreactor channel and a sample injected into the microreactor channel during analysis.

  The micropump unit 1 shown in FIGS. 1 and 2 includes three substrates: a silicon substrate 7, a glass substrate 8 thereon, and a glass substrate 9 thereon. The substrate 7 and the substrate 8 and the substrate 8 and the substrate 9 are joined by anodic bonding, respectively.

The micropump 2 is constituted by an internal space between the silicon substrate 7 and the glass substrate 8 bonded thereto by anodic bonding.
The substrate 7 is obtained by processing a silicon wafer into a predetermined shape by a photolithography technique. For example, by fine processing including formation of an oxide film on the silicon substrate surface, resist application, resist exposure and development, oxide film etching, silicon etching by ICP (Inductively Coupled Plasma), etc. A pressurizing chamber 12, a first channel 13, a first liquid chamber 15, a second channel 14, and a second liquid chamber 16 are formed.

  At the position of the pressurizing chamber 12, the silicon substrate is processed into a diaphragm, and a piezo actuator 11 made of lead zirconate titanate (PZT) ceramic or the like is attached to the outer surface thereof.

  The micro pump 2 is driven as follows by the voltage applied to the piezo actuator 11. When the piezoelectric actuator 11 vibrates by applying a voltage having a predetermined waveform, the silicon diaphragm at the position of the pressurizing chamber 12 vibrates with it, thereby increasing or decreasing the volume of the pressurizing chamber 12. The first flow path 13 and the second flow path 14 have the same width and depth, and the length of the second flow path 14 is longer than that of the first flow path 13.

  In the first flow path 13, when the differential pressure increases, turbulent flow is generated in the flow path and the flow path resistance increases. On the other hand, in the second flow path 14, since the flow path width is long, laminar flow tends to occur even if the differential pressure increases, and the change rate of the flow path resistance with respect to the change in differential pressure is smaller than that in the first flow path 13. .

  The difference in flow rate resistance change ratio with respect to the change in differential pressure in the first flow channel 13 and the second flow channel 14 is not necessarily due to the difference in the length of the flow channel, but in other geometrical differences. It may be based.

  When a voltage having the waveform shown in FIG. 3A is applied to the piezo actuator 11, the diaphragm is quickly displaced in the direction toward the inside of the pressurizing chamber 12 during the period T1 when the voltage suddenly rises. The volume of the pressurizing chamber 12 decreases while a large differential pressure is applied to the 13 and the second flow path 14.

  Next, in period T2, the voltage is maintained at a constant value e1, and then in period T3 in which the voltage gradually falls, the diaphragm is slowly displaced from the pressurizing chamber 12 toward the outside thereof, and the first flow path 13 and The volume of the pressurizing chamber 12 increases while a small differential pressure is applied to the second flow path 14.

By repeatedly applying the trapezoidal voltage waveform at intervals of the period T4, the liquid is fed in the direction A in FIG.
On the other hand, when a voltage having the waveform shown in FIG. 3B is applied to the piezo actuator 11, the diaphragm is gradually displaced in the direction toward the inside of the pressurizing chamber 12 during the period T5 when the voltage gradually rises. While a small differential pressure is applied to the flow path 13 and the second flow path 14, the volume of the pressurizing chamber 12 decreases.

  Next, in period T6, the voltage is maintained at a constant value e1, and then in period T7 in which the voltage falls steeply, the diaphragm is quickly displaced from the pressurizing chamber 12 toward the outside thereof, and the first flow path 13 and The volume of the pressurizing chamber 12 increases while a large differential pressure is applied to the second flow path 14.

By repeatedly applying the trapezoidal voltage waveform at intervals of the period T8, the liquid is fed in the direction B in FIG.
In this embodiment, as the trapezoidal voltage waveform in FIG. 3B when the liquid is fed in the B direction, the inverted trapezoidal voltage waveform in FIG. 3A when the liquid is fed in the A direction is used. The trapezoidal voltage waveform in FIG. 3A and the trapezoidal voltage waveform in FIG. 3B are asymmetrical to each other.

That is, the voltage rise time T1 in the drive voltage waveform when liquid is fed in the A direction is shorter than the voltage fall time T7 in the drive voltage waveform when liquid is fed in the B direction.
Therefore, the short rising time T1 in the trapezoidal voltage waveform in FIG. 3A can increase the liquid feeding speed in the A direction, which is the main direction of liquid feeding, and the rising edge in the trapezoidal voltage waveform in FIG. The falling time T7 is longer than the rising time T1 of the trapezoidal voltage waveform in FIG. 3A to such an extent that there is no practical problem with the liquid feeding speed in the B direction. The generation of bubbles is suppressed even during liquid feeding in the B direction, which is likely to occur.

  A flow path 10 is patterned on the substrate 9, and the micro pump 2 communicates with the micro flow path of the inspection chip on the downstream side of the flow path 10 by aligning with the openings 32 a to 32 k of the microreactor in FIG. 4. An opening 5 is provided for this purpose.

  The upstream side of the channel 10 is communicated with the micropump 2 through the channel provided in the substrate 7 through the through hole 6 b of the substrate 8. The upstream side of the micropump 2 communicates with the opening 4 provided in the glass substrate 9 from the flow path provided in the substrate 7 through the through hole 6 a of the substrate 8. The opening 4 is connected to a driving liquid tank (not shown). The opening 4 is connected to the driving liquid tank through, for example, PDMS (polydimethylsiloxane) packing.

The openings 5a, 5b, and 5c communicate with the openings 32c, 32d, and 32e of the microreactor in FIG. 4 (note that only a part of the entire micropump unit is shown in FIG. 2). The micropump 2 sends the driving liquid through the flow path 10, the opening 5a, and the opening 32c, pushes the reagent stored in the reagent storage section 33a downstream, and sends the driving liquid through the flow path 10, the opening 5b, and the opening 32d. The reagent stored in the reagent container 33b is pushed downstream, the driving liquid is fed through the channel 10, the opening 5c, and the opening 32e to push the reagent stored in the reagent container 33c downstream.

  Reagents stored in the reagent storage units 33a to 33c are water repellent valves (not shown) provided at the downstream ends of the reagent storage units 33a to 33c by separate micro pumps communicating with the openings 32c to 32e, respectively. The three types of reagents are mixed in the reagent mixing flow path 35 which is a flow path following the flow path and flows into the merging portion 41.

  The mixed reagent mixed in the reagent mixing flow path 35 and sent out to the mixed reagent delivery flow path 36 joins the sample accommodated in the flow path-shaped sample receiving portion 37 in the merge portion 38. The mixed reagent is pushed downstream with the driving liquid by the micro pump 2 communicated with the opening 32b, and the sample is pushed downstream with the driving liquid by the micro pump 2 communicated with the opening 32a. The mixed solution of the mixed reagent and the sample is sent to the reaction unit 39, and the gene amplification reaction is started by heating.

  The liquid after the reaction is sent to the detection unit 40, and the target substance is detected by, for example, an optical detection method. In addition, each reagent (for example, a liquid for stopping the reaction between the mixed reagent and the sample, a substance to be detected) previously stored in the flow path ahead of these openings by the separate micro pumps 2 communicating with the openings 32f to 32j. Liquid for performing necessary processing such as labeling, cleaning liquid, and the like) are extruded downstream at a predetermined timing and fed.

  In the micropump 2 in FIG. 2, the liquid in the A direction is obtained by pushing the liquid used for reaction and detection in the flow path of the microreactor 30 such as merging of the reagents, liquid feeding of the reagent and sample to the reaction unit 39, Used when sending liquid.

  On the other hand, the liquid feeding in the B direction is used when the reagent is shaken back and forth in the reaction unit 39 or the like, or the liquid that has advanced too far downstream is slightly returned. Is low, practical problems are unlikely to occur even if the feeding speed is somewhat slow.

  If the micropump 2 is controlled by the voltage waveform of the present embodiment, quick liquid feeding in the A direction can be executed in the flow path in the microreactor 30, and also when the liquid is fed in the B direction, Is less likely to generate bubbles.

  As mentioned above, although this invention was demonstrated based on the Example, this invention is not limited to this Example, In the range which does not deviate from the summary, various deformation | transformation and a change are possible.

FIG. 1 is a cross-sectional view of a micropump unit used in an embodiment of the present invention. FIG. 2 is a perspective view of the micropump unit of FIG. FIG. 3A is a graph showing the drive voltage waveform and the amount of liquid delivered during liquid feeding in the main direction (A direction), and FIG. 3B is the time when liquid feeding in the reverse direction (B direction). 5 is a graph showing a drive voltage waveform and a liquid delivery amount in FIG. FIG. 4 is a view showing a microreactor that feeds liquid using the micropump unit of FIG. FIGS. 5 (a) and 5 (b) show a conventional driving voltage waveform and the amount of liquid delivered when the micropump is fed, and FIG. 5 (a) shows the second from the first flow path by the micropump. FIG. 5B is a graph showing the drive voltage waveform and the amount of liquid delivered when liquid is delivered in the direction toward the flow path, and FIG. 5B is the drive during liquid delivery in the direction from the second flow path toward the first flow path. It is the graph which showed the voltage waveform and the delivery amount of the liquid.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Micro pump unit 2 Micro pump 3 Chip connection part 4 Opening 5a-5c Opening 6a, 6b Through-hole 7 Substrate 8 Substrate 9 Substrate 10 Channel 11 Piezo actuator 12 Pressurization chamber 13 First channel 14 Second channel 15 First 1 liquid chamber 16 2nd liquid chamber 30 Microreactor 32a-32k Opening 33a-33c Reagent storage part 35 Reagent mixing flow path 36 Mixed reagent delivery flow path 37 Sample receiving part 38 Merge part 39 Reaction part 40 Detection part 41 Merge part

Claims (6)

A first flow path in which the flow path resistance changes according to the differential pressure;
A second flow path whose rate of change in flow path resistance with respect to a change in differential pressure is smaller than the first flow path;
A pressurization chamber connected to the first flow path and the second flow path;
An actuator for changing the internal pressure of the pressurizing chamber;
A method of sending liquid in both directions using a micropump equipped with
The actuator is driven by a first drive voltage waveform in which a substantially trapezoidal voltage waveform is repeated, and liquid is fed in the direction from the first flow path to the second flow path,
The actuator is driven by a second drive voltage waveform in which a substantially trapezoidal voltage waveform is repeated, and liquid is fed in the direction from the second flow path to the first flow path,
A liquid feeding method using a micropump, characterized in that the voltage rise time in the first drive voltage waveform is shorter than the voltage fall time in the second drive voltage waveform. A driving liquid injection unit provided upstream of the microreactor to which the liquid used for the reaction is sent in the flow path in the plate-shaped chip is connected to the second flow path side of the micropump,
The actuator is driven by the first driving voltage waveform, the driving liquid is sent in the direction from the first flow path to the second flow path, and the driving liquid injected from the driving liquid injection portion into the flow path of the microreactor. The liquid feeding method using a micropump according to claim 1, wherein the liquid used for the reaction is pushed downstream and fed.   The actuator is driven by the second driving voltage waveform, the driving liquid is sent in the direction from the second flow path to the first flow path, and the liquid used for the reaction connected in series with the driving liquid is set to be downstream. 3. The liquid feeding method using a micropump according to claim 2, wherein the liquid is fed to the driving liquid injection part side in the reverse direction. (I) a first flow path in which the flow path resistance changes according to the differential pressure;
A second flow path whose rate of change in flow path resistance with respect to a change in differential pressure is smaller than the first flow path;
A pressurization chamber connected to the first flow path and the second flow path;
An actuator for changing the internal pressure of the pressurizing chamber;
A micropump that can feed liquids with
(Ii) means for generating a first drive voltage waveform and a second drive voltage waveform in which a substantially trapezoidal voltage waveform for driving the actuator is repeated;
With
The voltage rise time in the first drive voltage waveform is shorter than the voltage fall time in the second drive voltage waveform,
The actuator is driven by the first drive voltage waveform to send liquid in the direction from the first flow path to the second flow path,
A liquid feed system using a micropump, wherein the actuator is driven by a second drive voltage waveform to feed liquid in a direction from the second flow path toward the first flow path. A liquid used for the reaction is previously stored in the flow path in the plate-shaped chip, and includes a microreactor in which a reaction using a reagent is performed in the flow path.
In the upstream of the flow path of the microreactor, a driving liquid injecting unit for injecting a driving liquid for sending the liquid used for the reaction is provided,
A driving liquid injection part of the microreactor communicates with the second flow path side of the micropump,
The actuator is driven by the first drive voltage waveform to send the drive liquid in the direction from the first flow path to the second flow path, and the drive liquid injected from the drive liquid injection section into the flow path of the microreactor 5. The liquid feeding system using a micropump according to claim 4, wherein the liquid used for the reaction is pushed downstream and fed.   The actuator is driven by the second driving voltage waveform, the driving liquid is sent in the direction from the second flow path to the first flow path, and the liquid used for the reaction connected in series with the driving liquid is set to be downstream. 6. The liquid feeding system using a micropump according to claim 5, wherein the liquid is fed to the driving liquid injecting portion in the reverse direction.

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