Methods, systems, and computer program products for detecting a droplet

Patent metadata

Field	Value
Publication number	US-10603659-B2
Application number	US-201715719007-A
Country	US
Kind code	B2
Filing date	Sep 28, 2017
Priority date	Aug 15, 2014
Publication date	Mar 31, 2020
Grant date	Mar 31, 2020

Abstract

Methods, systems, and computer program products for detecting formation of a droplet at a distal end of a pipette tip attached to a pipette. The methods, systems, and computer program products provide dispensing a fluid from the pipette tip, measuring pipette pressure in real time at an internal portion of the pipette while the fluid is dispensed, determining a plurality of pressure differences, estimating a plurality of rate of change in pipette pressure values during a given time interval, detecting formation of the droplet responsive to determining certain conditions are met, and stopping the dispensing of the fluid from the pipette tip or moving the pipette when the droplet is detected.

First claim

What is claimed is:

1. A computer system, comprising:
a processor; and
a memory coupled to the processor, the memory comprising computer readable program code embodied therein that, when executed by the processor, causes the processor to perform operations comprising:
dispensing a fluid from a pipette tip attached to a pipette;
measuring pipette pressure in real-time at an internal portion of the pipette at given sampling time intervals during the step of dispensing the fluid from the pipette tip to generate a plurality of pipette pressure values, wherein the pipette pressure is measured using a pipette pressure detector that measures pipette pressure at the internal portion of the pipette;
determining a plurality of pressure differences, wherein the step of determining the plurality of pressure differences comprises calculating a difference between a most recently measured pipette pressure value and at least one pipette pressure value measured prior to the most recently measured pipette pressure value;
estimating a plurality of rate of change in pipette pressure values during a given time interval, wherein the estimating the plurality of rate of change in pipette pressure values during the given time interval comprises estimating a first rate of change based on a first pressure difference from the plurality of pressure differences over a first portion of the given time interval and estimating a second rate of change based on a second pressure difference from the plurality of pressure differences over a second portion of the given time interval, weighting the first and second estimated rate of change by about 0% to 49% to generate first and second weighted estimated rates of change, calculating a first sum by summing the first weighted estimated rate of change with a first previously calculated rate of change weighted by about 51% to 100%, calculating a second sum by summing the second weighted estimated rate of change with a second previously calculated rate of change weighted by about 51% to 100%, and comparing the first and second sums with an upper pressure related threshold and a lower pressure related threshold;
detecting formation of a droplet at a distal end of the pipette tip based on determining that the first sum is greater than or equal to the upper pressure related threshold and the second sum is less than or equal to the lower pressure related threshold; and
stopping the dispensing of the fluid from the pipette tip when the droplet is detected or moving the pipette when the droplet is detected.

2. The computer system of claim 1 , wherein the plurality of rate of change in pipette pressure values changes over a period of time.

3. The computer system of claim 1 , wherein the upper pressure related threshold and/or the lower pressure related threshold is/are determined using a given rate of dispense.

4. The computer system of claim 1 , wherein the droplet has a volume in a range of about 0.5 μL, to about 3.5 μL.

5. The computer system of claim 1 , wherein at least one of the plurality of rate of change in pipette pressure values corresponds to a rate of change in pipette pressure while the pipette is dispensing a gas and at least one of the plurality of rate of change in pipette pressure values corresponds to a rate of change in pipette pressure while the pipette is dispensing a liquid.

6. The computer system of claim 1 , wherein the memory comprises further computer readable program code embodied therein that, when executed by the processor, causes the processor to perform the operation of stopping the dispensing of the fluid from the pipette tip responsive to detecting the formation of the droplet.

7. The computer system of claim 1 , wherein the memory comprises further computer readable program code embodied therein that, when executed by the processor, causes the processor to perform further operations comprising detecting a clog in the pipette tip attached to the pipette.

8. The computer system of claim 7 , wherein the computer readable program code that causes the processor to perform the detecting of the clog in the pipette tip attached to the pipette comprises computer readable program code that causes the processor to perform operations comprising:
determining that a given number of rate of change in pipette pressure values of the plurality of rate of change in pipette pressure values are greater than or equal to a first clog related threshold, or
determining that an updated pressure difference corresponding to a most recently measured pipette pressure value of the plurality of pipette pressure values is greater than a second clog related threshold.

9. A computer program product comprising:
a non-transitory computer readable storage medium having computer readable code embodied in the medium, the computer readable code comprising:
computer readable code that, when executed by a processor, causes the processor to perform operations comprising:
dispensing a fluid from a pipette tip attached to a pipette;
measuring pipette pressure in real-time at an internal portion of the pipette at given sampling time intervals during the dispensing the fluid from the pipette tip to generate a plurality of pipette pressure values, wherein the pipette pressure is measured using a pipette pressure detector that measures pipette pressure at the internal portion of the pipette;
determining a plurality of pressure differences, wherein the determining the plurality of pressure differences comprises calculating the difference between at least one previously measured pipette pressure value and a most recently measured pipette pressure value;
estimating a plurality of rate of change in pipette pressure values during a given time interval, wherein the estimating the plurality of rate of change in pipette pressure values during the given time interval comprises estimating a first rate of change based on a first pressure difference from the plurality of pressure differences over a first portion of the given time interval and estimating a second rate of change based on a second pressure difference from the plurality of pressure differences over a second portion of the given time interval, weighting the first and second estimated rate of change by about 0% to 49% to generate first and second weighted estimated rates of change, calculating a first sum by summing the first weighted estimated rate of change with a first previously calculated rate of change weighted by about 51% to 100%, calculating a second sum by summing the second weighted estimated rate of change with a second previously calculated rate of change weighted by about 51% to 100%, and comparing the first and second sums with an upper pressure related threshold and a lower pressure related threshold;
detecting formation of a droplet at a distal end of the pipette tip based on determining that the first sum is greater than or equal to the upper pressure related threshold and the second sum is less than or equal to the lower pressure related threshold; and
stopping the dispensing of the fluid from the pipette tip when the droplet is detected or moving the pipette when the droplet is detected.

10. The computer program product of claim 9 , wherein the plurality of rate of change in pipette pressure values changes over a period of time.

11. The computer program product of claim 9 , wherein the upper pressure related threshold and/or the lower pressure related threshold is/are determined using a given rate of dispense.

12. The computer program product of claim 9 , wherein at least one of the plurality of rate of change in pipette pressure values corresponds to a rate of change in pipette pressure while the pipette is dispensi

Assignees

• Bio Merieux Inc

Inventors

• Luebbert Daniel Oliver
• Pingel Daniel Joseph
• Harrison Joel Patrick
• Pionke Jeremey Joseph

Classifications

• B01L3/0268

  using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries · CPC title

• B01L3/021 Primary

  Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids · CPC title

• G01N35/00623

  of instruments · CPC title

• B01L2400/02

  Drop detachment mechanisms of single droplets from nozzles or pins · CPC title

• G01N2035/103

  using disposable tips · CPC title