Patent Application
20180272345
This application is based upon and claims the benefit of priority from Japanese Patent Application No. 2017-059797, filed Mar. 24, 2017, the entire contents of which are incorporated herein by reference.
Embodiments described herein relate generally to a droplet dispensing apparatus.
For use in biological and pharmaceutical research and development, medical diagnosis or testing, or agricultural experiment, analytic devices and testing methods involving dispensing solution in volumes with in a picoliter (pL) to microliter (μL) range are often used.
For improved speed in testing and evaluation, a droplet ejecting device typically ejects liquid droplets simultaneously from multiple nozzles into different wells of a microplate (also referred to as a multi-well plate) or the like.
When liquid droplets are being dispensed simultaneously from a plurality of nozzles, there is a possibility that some of nozzles may not discharge the liquid as intended. In such a case, the intended amount of liquid is not dispensed from malfunctioning nozzle, which may cause erroneous evaluation results in some testing applications.
In general, according to one embodiment, a droplet dispensing apparatus includes a droplet ejecting array having a plurality of nozzle groups, from each of which solution can be ejected into a well opening of a microplate on a baseline, each nozzle group including a plurality of nozzles arranged in columns in a first direction and rows in a second direction that intersects the first direction, and the plurality of nozzles being arranged in a line in a third direction, a light emitting unit configured to emit light along an optical path in the third direction oblique with respect to the first direction and the second direction, a light receiving unit disposed along the optical path and configured to receive light from the light emitting unit, the light receiving unit being on an opposite side of the droplet ejecting array from the light emitting unit, and a controller configured to receive signals from the light receiving unit according to light intensity as detected by the light receiving unit, and adjust ejection timings such that each of the plurality of nozzle groups ejects at a different timing.
Hereinafter, droplet dispensing apparatuses according to example embodiments will be described with reference to the drawings. It should be noted, that the particular embodiments explained below are some possible examples of a droplet dispensing apparatus according to the present disclosure and do not limit the possible configurations, specifications, or the like of droplet dispensing apparatuses according to the present disclosure.
An example of a droplet dispensing apparatus 1 according to a first embodiment is described with reference to
The droplet dispensing apparatus 1 has a main body 1A, which includes a base plate 3 of the rectangular plate shape and a mounting module 5. In the present embodiment, a microplate 4, which may also be referred to as a receiving portion, a multiwell plate, or a microwell plate in some contexts, has 96 wells into which a solution can be dispensed. Microplates having 96 wells are commonly used in a biochemistry research and clinical examination. However, the microplate 4 is not limited to having 96 wells and may have any other number of wells, such as 384 wells, 1536 wells, 3456 wells, or 6144 wells.
The microplate 4 is located at a middle position of the base plate 3 and can be secured to and detached from a plate attaching portion 3a of the base plate 3. A pair X-direction guide rails 6a and 6b extending in the X-direction is provided at both sides of the microplate 4. The ends of each of the X-direction guide rails 6a and 6b are respectively fixed to fixing supports 7a and 7b protruding on the base plate 3.
A Y-direction guide rail 8 extending in the Y-direction is provided between the X-direction guide rails 6a and 6b. Both ends of the Y-direction guide rail 8 are respectively fixed to X-direction movable supports 9 which can slide in the X-direction along the X-direction guide rails 6a and 6b.
A Y-direction movable support 10 is provided, on which the mounting module 5 is movable in the Y-direction along the Y-direction guide rail 8. The mounting module 5 is mounted on the Y-direction movable support 10. The droplet ejecting device 2, which serves as a droplet ejecting unit, is fixed to the mounting module 5. Thus, the droplet ejecting device 2 can move to any position in the X- and Y-directions, which are orthogonal to each other in this instance, by a combination of a movement of the Y-direction movable support 10 moving in the Y-direction along the Y-direction guide rail 8 and a movement of the X-direction movable supports 9 moving in the X-direction along the X-direction guide rails 6a and 6b. Furthermore, the droplet ejecting device 2 can be configured to be detachably mounted on the mounting module 5.
The droplet ejecting device 2 according to the first embodiment has a flat base plate 21. As illustrated in
As illustrated in
On the electrical circuit board 23, an electrical circuit board wiring 24 is patterned on a surface opposite to the recessed portion 21b. The electrical circuit board wiring 24 has three wiring patterns 24a, 24b, and 24c formed therein, which are respectively connected to a terminal portion 131c of a lower electrode 131 and two terminal portions 133c of an upper electrode 133.
At one end portion of the electrical circuit board wiring 24, a control signal input terminal 25 for receiving an external control signal is formed. At the other end portion of the electrical circuit board wiring 24, an electrode terminal connector 26 is formed. The electrode terminal connector 26 electrically connects the lower electrode terminal portion 131c and the upper electrode terminal portions 133c formed in the droplet ejecting array 27.
Furthermore, the base plate 21 has a through-hole for the droplet ejecting opening 21d. The droplet ejecting opening 21d is a rectangular through-hole as illustrated in
The droplet ejecting array 27 illustrated in
As illustrated in
The droplet ejecting array 27 has a nozzle group including a plurality of the nozzles 110 arranged side by side in a X-Y plane that is parallel to the X-direction and the Y-direction, as illustrated in
Furthermore, in the droplet ejecting array 27 according to the present embodiment, one nozzle group is located at a position corresponding to one opening 22a of one of the eight solution holding containers 22. Twelve nozzles 110 in one nozzle group 171 are arranged only within one well opening 4b of the microplate 4.
The diaphragm 120 is formed, for example, integrally with the pressure chamber structure 200. The drive element 130 is formed for each nozzle 110. The drive element 130 has an annular shape surrounding the nozzle 110. The shape of the drive element 130 is not limited, and can be, for example, a C shape formed with a part of the circular ring removed.
The diaphragm 120 deforms in the thickness direction thereof by an operation of the drive element 130, which is in a planar shape. The droplet ejecting device 2 ejects a solution supplied to each nozzle 110 according to a pressure change occurring in a pressure chamber 210 of the pressure chamber structure 200 due to the deformation of the diaphragm 120.
The main body 1A of the droplet dispensing apparatus 1 includes a droplet detection unit 230 illustrated in
As illustrated in
Along the optical path 233, horizontally-polarized light is emitted from the light emitting unit 231 toward the light receiving unit 232. The droplet detection unit 230 is driven by the control unit 235. Then, when droplets block light along the optical path 233, light intensity received by the light receiving unit 232 is reduced. The control unit 235 receives an output corresponding to the light intensity detected by the light receiving unit 232. When the detected light intensity is less than a specified amount, the control unit 235 detects droplets are being ejected from the nozzles 110.
In the main body 1A of the droplet dispensing apparatus 1, the optical path 233 is arranged obliquely with respect to the second direction along the columns of nozzles 110 in a nozzle group. In the example embodiment described herein, the droplet ejecting array 27 is adhesively fixed to the droplet ejecting opening 21d of the base plate 21 of the droplet ejecting device 2, and located obliquely with respect to the base plate 21.
Furthermore, the control unit 235 includes the ejection timing adjustment unit 234, which controls timing of ejecting of droplets from the droplet ejecting device 2. The ejection timing adjustment unit 234 adjusts ejection timing of droplets from the eight nozzle groups 171 (nozzle groups 171a to 171h) at different timings.
The terminal portion 131c of the lower electrode 131 and the terminal portions 133c of the upper electrode 133 are formed for each of the eight nozzle groups and are connected to the ejection timing adjustment unit 234 via the electrical circuit board wiring 24.
As illustrated in
After that, the control unit 235 applies a drive pulse having a pulse width t1 and a voltage Vt to drive the second nozzle group 171b after elapse of a predetermined interval t2.
Subsequently, the control unit 235 sequentially applies drive pulses (each having a pulse width t1 and a voltage Vt to drive the third nozzle group 171c through the eighth nozzle group 171h at intervals of the predetermined interval t2. After the eighth nozzle group 217h is driven, a sequence of the drive pluses to drive the first nozzle group 217a through the eighth nozzle group 217h is repeated.
That is, after the eighth nozzle group 171h has been driven at time t0+8×(t1+t2), the control unit 235 re-applies a drive pulse having the pulse width t1 and the voltage Vt to drive the first nozzle group 171a. After that, the control unit 235 sequentially applies drive pulses each having the pulse width t1 and the voltage Vt to the drive the second nozzle group 171b through the eighth nozzle group 171h at the predetermined intervals t2.
In the droplet dispensing apparatus 1 according to the present embodiment, the droplet ejecting array 27 of the droplet ejecting device 2 is mounted on the mounting module 5. When the droplet ejecting device 2 is use, a predetermined amount of solution is supplied to the solution holding container 22 from the top open portion 22b of the solution holding container 22 by a pipette or the like (not illustrated). The solution is held at the inner surface of the solution holding container 22. The opening portion 22a at the bottom portion of the solution holding container 22 communicates with the droplet ejecting array 27. The solution held in the solution holding container 22 flows into each pressure chamber 210 of the droplet ejecting array 27 via the opening portion 22a.
A voltage control signal that is input to the control signal input terminal 25 is transmitted from the electrode terminal connector 26 to the terminal portion 131c of the lower electrode 131 and the terminal portions 133c of the upper electrode 133. In response to the voltage control signal applied to the drive element 130, the diaphragm 120 deforms to change the volume of the pressure chamber 210, so that the solution is ejected as solution droplets from the nozzle 110 of the droplet ejecting array 27. In the present embodiment, the solution droplets are simultaneously dropped from twelve nozzles 110 to one well opening 4b of the microplate 4. Thus, a predetermined amount of solution is dropped from the nozzle 110 to each well opening 4b of the microplate 4.
An amount of solution that is dropped is controlled by a number of repetitions of one-droplet dropping from each nozzle 110, and thus it is possible to control dropping of solution on the order of picoliter (pL) to microliter (μL).
In the present embodiment, the droplet detection unit 230 and the ejection timing adjustment unit 234 are driven during an operation of solution dropping from the nozzles 110 of the droplet ejecting array 27. The droplet detection unit 230 detects droplets are being ejected from the nozzles 110 by detecting a reduction in the light intensity detected by the light receiving unit 232 when light in the optical path 233 is blocked by the droplets.
An operation of detecting droplets via the droplet detection unit 230 in the present embodiment will be described with reference to
As illustrated in
Furthermore, as illustrated in
During an operation of the ejection timing adjustment unit 234, the control unit 235 adjusts ejection timings for the eight nozzle groups 171. For example, as illustrated in
In the droplet dispensing apparatus 1 according to the first embodiment, the droplet detection unit 230 is driven at the time of an operation of dropping droplets from the nozzles 110 of the droplet ejecting array 27. In the droplet detection unit 230 as illustrated in
In the example embodiment described herein, the droplet dispensing apparatus 1 has the ejection timing adjustment unit 234. During an operation of the ejection timing adjustment unit 234, the control unit 235 adjusts ejection timings for the eight nozzle groups 171. For example, as illustrated in
Accordingly, in the example embodiment described herein, when droplets are ejected from the eight nozzle groups 171 that are arrayed along the optical path 233 between the light emitting unit 231 and the light receiving unit 232 of the droplet detection unit 230, no two or more nozzle groups 171 among the eight nozzle groups 171 are driven at the same timing. Therefore, the light receiving unit 232 detects droplets being dropped from one nozzle group at a time. As a result, even with eight nozzle groups 171h arranged in a line along the optical path 233 between the light emitting unit 231 and the light receiving unit 232, the control unit 235 can individually detect droplets being ejected from the eight nozzle groups 171.
A piezoelectric element may be made of a lead-free material that is lower in piezoelectric property than a piezoelectric element including a lead component, for example, PZT (Pb(Zr,Ti)O3: lead zirconate titanate), which contains a lead component. Therefore, in the case of using the piezoelectric element made of a lead-free material, since the amount of displacement of the diaphragm 120 when being driven is smaller than that of the piezoelectric element made from PZT, an amount of solution per one droplet is small.
In the example embodiment described herein, a plurality of nozzles 110 (twelve arrayed in three rows and four columns) is disposed in one nozzle group for one well opening 4b. Thus, dropping of a required amount of solution can be completed in a short time even with use of the piezoelectric element having a lower piezoelectric property. Therefore, dropping of a required amount of solution can be completed in a short time even with respect to all well openings 4b of the microplate 4.
In the second embodiment, a second droplet ejecting unit 251 in addition to the droplet ejecting array 27 is provided. The second droplet ejecting unit 251 is provided with a supporting mechanism which supports the second droplet ejecting unit 251 in such a way as to be movable to any position in the X- and Y-directions separately from the droplet ejecting device 2.
The second droplet ejecting unit 251 includes, for example, a water tank (not specifically illustrated). The second droplet ejecting unit 251 may include a tank that contains the same solution as that contained in the droplet ejecting array 27.
In the second embodiment, after a predetermined amount of solution has been dropped from the droplet ejecting array 27 into each well opening 4b of the microplate 4, after elapse of a preset time, solution (or water) is additionally ejected from the second droplet ejecting unit 251 into each well opening 4b of the microplate 4. This makes it possible to prevent solution held in each well opening 4b of the microplate 4 from drying.
For example, in a high-density microplate, cells may be dried by solution evaporation due to a prolonged dispensing time due to a large number of wells. In such a case, the second droplet ejecting unit 251 in the second embodiment performs additional dispensing of a solution enables to prevent or reducing drying. This permits high-efficiency experiments to be performed by using a high-density microplate.
Furthermore, the supporting mechanism for the second droplet ejecting unit 251 may be able to perform parallel processing of dispensing droplets while moving in parallel with or perpendicularly to the movement of the droplet ejecting array 27.
In the third embodiment, a closed box component 261 encloses the microplate 4 and a spray device 262 spraying a humidifying solution inside the closed box component 261 on the base plate 3. The closed box component 261 includes, for example, a frame portion having a high-rigidity frame structure and a cover made from an elastic material closing a space between the framing parts of each frame. The closed box component 261 can be hermetically sealed by the frame portion and the cover.
The spray device 262 includes, for example, a water tank (not illustrated). The spray device 262 may further include a tank that contains the same solution as that contained in the droplet ejecting array 27. The spray device 262 is located inside the closed box component 261, and sprays solution to the internal space of the closed box component 261 for drying prevention.
In the present embodiment, after a predetermined amount of solution has been dropped from the droplet ejecting array 27 into each well opening 4b of the microplate 4, when a preset time elapses, droplets for preventing drying are sprayed from the spray device 262 to the internal space of the closed box component 261. The spray device 262 may be configured such that droplets for drying prevention are sprayed at the same time as the start of a solution dropping operation from the droplet ejecting array 27.
This makes it possible to prevent solution held in well openings 4b of the microplate 4 from drying or reducing.
Furthermore, in the droplet ejecting array 27, a needle-like injection member 273 is provided. At the tip of the injection member 273, there is provided with an actuator which is capable of ejecting droplets in the order of pL.
In the microplate 4, in the standby state (when not in use), the opening of the well opening 4b is closed by the lid 271. In this state, the notch 272 of the lid 271 is closed.
At the time of an operation of solution dropping from the droplet ejecting array 27, the tip of the injection member 273 is pressed into the notch 272 of the lid 271 as illustrated in
Furthermore, after a specified amount of solution is ejected from the injection member 273, the injection member 273 is withdrawn to the outside of the microplate 4. At this time, the lid 271 elastically returns to a state in which the peripheral portions on both sides of the notch 272 are closed. Therefore, the well opening 4b of the microplate 4 is closed by the lid 271. Thus, since the internal space of the well opening 4b of the microplate 4 is kept in an airtight state by the lid 271, droplets injected into the well opening 4b of the microplate 4 are prevented from evaporating.
As a result, solution held in each well opening 4b of the microplate 4 can prevented from and drying is reduced.
While certain embodiments have been described, these embodiments have been presented by way of example only, and are not intended to limit the scope of the inventions. Indeed, the novel embodiments described herein may be embodied in a variety of other forms. Furthermore, various omissions, substitutions and changes in the form of the embodiments described herein may be made without departing from the spirit of the inventions. The accompanying claims and their equivalents are intended to cover such forms or modifications as would fall within the scope and spirit of the inventions.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2017-059797 | Mar 2017 | JP | national |
