System and method for dispensing fluid droplets of known volume and generating very low fluid flow rates

• US 6,213,354 B1
• Filed: 12/29/1999
• Issued: 04/10/2001
• Est. Priority Date: 12/29/1999
• Status: Expired due to Fees

• Current Assignee: Elite Engineering Corporation
• Original Assignee: Elite Engineering Corporation
• Inventors: Kay, Robert L.
• Primary Examiner(s): JACYNA, J CASIMER
• Application Number:
  US09/474,559
• Time in Patent Office: 468 Days
• Field of Search: 222/420-422, 222/1, 222/14, 222/52, 222/55
• US Class Current: 222/420
• CPC Class Codes: A61B 5/150015 Source of blood
• CPC Class Codes: A61B 5/150229 Pumps for assisting the blood sampling
• CPC Class Codes: A61B 5/150946 Means for varying, regulating, indicating or limiting the speed or time of blood collection
• CPC Class Codes: A61B 5/155 Devices specially adapted for continuous or multiple sampling, e.g. at predetermined intervals devices loaded with multiple lancets simultaneously A61B5/15146
• CPC Class Codes: A61M 2205/3306 Optical measuring means
• CPC Class Codes: A61M 5/16804 Flow controllers
• CPC Class Codes: A61M 5/1689 Drip counters
• CPC Class Codes: B01L 3/0241 Drop counters; Drop formers making arrays for combinatorial libraries B01J19/0046; automation of dispensing for analysis G01N35/10
• CPC Class Codes: B01L 3/0262 using touch-off at substrate or container
• CPC Class Codes: G01N 2035/1041 Ink-jet like dispensers

Abstract

A system and method for dispensing fluid droplets of a known volume uses a control system using inner and outer control loops. The inner control loop includes a pump which pressurizes a fluid against an aperture, causing fluid to pass through the aperture and to a dispensing tip at a particular flow rate. The pressure of the fluid upstream of the aperture is measured and fed back to a controller, which also receives a setpoint input representative of desired dispensed volume. The outer control loop uses a droplet volume measuring system which determines the volume of the droplet that forms at the outlet of the dispensing tip as a result of the applied pressure, the value of which is also fed to the controller. The controller is arranged to maintain the pressure against the aperture (using the inner control loop) as needed to produce a flow rate which will quickly produce a droplet of the desired volume (as determined using the outer control loop), at which time the pressure is reduced to zero and the droplet dispensed

Claims

1. A low volume fluid droplet dispensing system, comprising:

a pump which provides a fluid at a pump outlet in response to a control signal,

tubing connected to the outlet of said pump,

an aperture in said tubing downstream of said pump, said fluid pressurized against said aperture by said pump and passing through said aperture at a flow rate which varies with the magnitude of the pressure applied by said pump on said fluid,

a pressure sensor which provides an output signal representative of the pressure of said fluid against said aperture,

a controller connected to receive a setpoint signal representative of a desired dispensed volume, said pressure sensor output signal, and a signal representative of dispensed fluid volume as inputs, and to produce said control signal to said pump as an output,

a dispensing tip on said tubing downstream of said aperture, and

a droplet volume measuring means arranged to measure the volume of a droplet that forms at the outlet of said dispensing tip, said droplet volume measuring means providing said signal representative of dispensed fluid volume to said controller, said pump, pressure sensor, and controller forming an inner control loop closed around the pressure against said aperture and said pump, droplet volume measuring means, and controller forming an outer control loop closed around droplet volume, said controller arranged to vary the pressure against said aperture to produce a droplet at said dispensing tip outlet having the desired dispensed volume.

2. The system of claim 1, wherein said pump is a syringe.

3. The system of claim 1, wherein said droplet volume measuring means comprises an imaging system and a processor, said imaging system arranged to produce a signal representative of an image of said droplet to said processor, said processor programmed to compute the volume of said drop based on said image signal and to output a signal representative of said volume to said controller.

4. The system of claim 3, wherein said imaging system comprises a camera.

5. The system of claim 1, wherein said dispensing tip bends in response to the weight of said droplet, said tip having a predetermined spring rate and said droplet having a predetermined density, said droplet volume measuring means comprising:

a reflective area on said tip which moves with said tip in response to the weight of said droplet,

a laser beam directed onto said reflective area,

a position sensitive detector (PSD) arranged to receive said reflected beam from said reflective area and to output a signal representative of the position of said beam, and

a processor arranged to determine the volume of said droplet based on said PSD output, said predetermined spring rate, and said predetermined density, and to output a signal representative of said volume to said controller.

6. The system of claim 1, wherein said aperture comprises a pinhole.

7. The system of claim 1, wherein said aperture comprises a nucleated membrane.

8. The system of claim 1, wherein said aperture comprises a ceramic filter.

9. The system of claim 1, further comprising a flexible cavity in said tubing between said pump and said aperture which acts to maintain said pressure within said tubing nearly constant for a changing volume of fluid in said tubing.

10. The system of claim 1, wherein said pump is a bi-directional pump such that the volume of said droplet can be increased or decreased.

11. A low volume fluid withdrawal and dispensing system, comprising:

a bi-directional pump which provides positive or negative pressure at a pump outlet in response to a control signal,

tubing connected to the outlet of said pump, said tubing at least partially filled with a first fluid,

an aperture in said tubing downstream of said pump, said first fluid pressurized against said aperture by said pump and passing through said aperture at a flow rate which varies with the magnitude of the pressure applied by said pump on said first fluid,

a pressure sensor which provides an output signal representative of the pressure of said first fluid against said aperture,

a controller connected to receive a setpoint signal representative of a desired dispensed volume, said pressure sensor output signal, and a signal representative of dispensed fluid volume as inputs, and to produce said control signal to said pump as an output,

a withdrawal/dispensing tip on said tubing downstream of said aperture, and

a droplet volume measuring means arranged to measure the volume of a droplet of a second fluid that forms at the outlet of said withdrawal/dispensing tip, said droplet volume measuring means providing said signal representative of dispensed fluid volume to said controller, said pump, pressure sensor, and controller forming an inner control loop closed around the pressure against said aperture and said pump, droplet volume measuring means, and controller forming an outer control loop closed around droplet volume,

said controller arranged to, with said withdrawal/dispensing tip immersed in a second fluid, command a negative pressure at said pump outlet to withdraw a quantity of said second fluid into said tip,

said controller further arranged to vary the pressure against said aperture to produce a droplet of said second fluid at said withdrawal/dispensing tip outlet having the desired dispensed volume.

12. The system of claim 11, wherein said first fluid and said second fluid are the same fluid.

13. The system of claim 11, wherein said first fluid and said second fluid are different fluids.

14. The system of claim 13, wherein said controller is further arranged to command a negative pressure at said pump outlet prior to said tip being immersed in said second fluid to withdraw a quantity of air into said tip so that, when said second fluid is drawn into said tip, a bolus of air is present between said first fluid and said withdrawn second fluid.

15. The system of claim 14, further comprising a means for moving said tip vertically and horizontally.

16. The system of claim 15, wherein said means for moving said tip is programmed to move said tip into and out of a container of said second fluid where said second fluid is withdrawn, and to a target location where said second fluid is dispensed.

17. The system of claim 16, wherein said means for moving said tip is further programmed to, when said droplet of said desired dispensed volume is formed at the outlet of said dispensing tip, lower said tip to a target surface to touch off said droplet.

18. The system of claim 16, wherein said means for moving said tip is further programmed to move said tip into a cleaning solution prior to moving said tip into and out of a container of said second fluid.

19. The system of claim 13, wherein said first fluid is water.

20. The system of claim 11, wherein a predetermined quantity of said second fluid adheres to said tip after said formed droplet is dispensed, said controller arranged to vary the pressure against said aperture to produce a droplet of said second fluid at said withdrawal/dispensing tip outlet having a volume that is greater than the desired dispensed volume by said predetermined quantity to compensate for said adhering fluid.

21. A method of dispensing a droplet of fluid having a desired volume, comprising the steps of:

providing a value representing the desired volume of a fluid droplet to be dispensed,

pressurizing a fluid against an aperture of a known size within a length of tubing,

measuring the pressure of said fluid against said aperture,

conveying the fluid which passes through said first aperture in response to said pressure to a dispensing tip,

measuring the volume of a droplet of said fluid as it forms at the outlet of said tip in response to said pressure,

computing a pressure value based on said volume measurement and said desired fluid volume value that, when used to pressurize said fluid against said aperture, results in said droplet quickly obtaining said desired volume,

adjusting the pressure of said fluid against said aperture to correspond to said computed pressure value, and

reducing said pressure on said fluid to zero when said droplet has obtained said desired volume.

22. The method of claim 21, further comprising the step of touching off said droplet to dispense it.

23. The method of claim 21, wherein said step of measuring the volume of said droplet comprises the steps of:

obtaining an image of said droplet, and

computing the volume of said droplet based on the size of said imaged droplet.

24. The method of claim 23, wherein said image is obtained with an imaging system which produces an image made up of pixels, further comprising the step of determining a droplet size-per-pixel value for use in determining the size of said droplet from said imaged droplet.

25. The method of claim 21, wherein said step of measuring the volume of said droplet comprises the steps of:

forming said droplet on the end of a dispensing tip which bends in response to the weight of said droplet, said droplet having a predetermined density and said tip having a predetermined spring rate,

reflecting a laser beam off of a portion of said dispensing tip which moves as said tip bends in response to the weight of said droplet,

detecting the position of said reflected beam,

computing the mass of said droplet based on the position of said reflected beam and said predetermined spring rate, and

computing the volume of said droplet based on its computed mass and said predetermined density.

26. A method of withdrawing fluid from a container and of dispensing a droplet of said fluid having a desired volume, comprising the steps of:

providing a value representing the desired volume of a droplet of a first fluid to be dispensed,

immersing the outlet of a dispensing tip in said first fluid,

establishing a negative pressure within a length of tubing connected to said dispensing tip to withdraw a quantity of said first fluid into said tip,

removing said tip from said first fluid,

pressurizing a second fluid against an aperture within said tubing,

measuring the pressure of said second fluid against said aperture,

conveying the fluid which passes through said first aperture in response to said pressure toward said dispensing tip via said tubing, thereby applying pressure to said quantity of said first fluid withdrawn into said tip,

measuring the volume of a droplet of said first fluid as it forms at the outlet of said tip in response to said pressure,

computing a pressure value based on said volume measurement and said desired fluid droplet volume value that, when used to pressurize said second fluid against said aperture, results in said droplet quickly obtaining said desired volume,

adjusting the pressure of said second fluid against said aperture to correspond to said computed pressure value, and

reducing said pressure on said second fluid to zero when said droplet has obtained said desired volume.

27. The method of claim 26, further comprising the step of touching off said formed droplet to dispense it.

28. The method of claim 27, further comprising the step of moving said tip from a first location near said first fluid to a target location where said droplet is touched off.

29. The method of claim 27, wherein a predetermined quantity of said second fluid adheres to said tip after said formed droplet is dispensed, said step of computing said pressure value further comprising increasing said computed pressure value as needed to compensate for said adhering fluid such that said dispensed volume is about equal to said desired volume.

30. The method of claim 26, further comprising the step of, prior to immersing the outlet of the dispensing tip in said first fluid, establishing a negative pressure within said length of tubing while the outlet of said dispensing tip is open to the atmosphere to withdraw a bolus of air into the tip such that, after said quantity of said first fluid is withdrawn into said tip, said bolus separates said first fluid from said second fluid.

31. The method of claim 26, further comprising the steps of, prior to immersing the outlet of the dispensing tip in said first fluid, immersing said tip in a cleaning solution and removing said tip from said cleaning solution.

32. The method of claim 26, wherein said first fluid and said second fluid are the same fluid.

33. The method of claim 26, wherein said first fluid and said second fluid are different fluids.

34. A fluid droplet dispensing tip and volume measuring system, comprising:

a channel having first and second ends, said channel having a predetermined spring rate along its length between said first and second ends,

an aperture formed at said second end of said channel, said channel arranged such that a fluid introduced at said first end is conveyed by said channel to said aperture, said aperture arranged such that fluid conveyed to said aperture by said channel forms into a droplet around said aperture, said channel fixed at said first end and extending freely and approximately horizontally from said fixed end, said predetermined spring rate such that said aperture end progressively droops with respect to said first end as the weight of said droplet increases, said droplet having a predetermined density,

a reflective area near said aperture that moves with said aperture as the weight of said droplet increases,

a laser beam directed onto said reflective area,

a position sensitive detector (PSD) arranged to receive said reflected beam from said reflective area and to output a signal representative of the position of said beam, and

a processor arranged to determine the volume of said droplet based on said PSD output, said predetermined spring rate, and said predetermined density, and to output a signal representative of said volume.

35. The dispensing tip of claim 34, wherein the diameter of said channel is such that fluid introduced at said first end is conveyed by said channel to said aperture end by surface tension.