Calibrating dispensing device performance for complex and/or non-aqueous liquids

• US 20070141709A1
• Filed: 12/16/2005
• Published: 06/21/2007
• Est. Priority Date: 12/16/2005
• Status: Active Grant

• Current Assignee: Artel Incorporated (Conagra Brands, Inc.)
• Original Assignee: Artel Ooo
• Inventors: Rogers, Alex, Bradshaw, John, Albert, Keith
• Granted Patent: US 8,003,405 B2
• Time in Patent Office: Days
• US Class Current: 436/8
• CPC Class Codes: G01F 25/0092 for metering by volume
• CPC Class Codes: G01N 1/38 Diluting, dispersing or mixing samples
• CPC Class Codes: G01N 21/25 Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
• CPC Class Codes: G01N 35/1016 Control of the volume dispensed or introduced
• CPC Class Codes: Y10T 436/10 Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/25625 Dilution

Abstract

A method for precisely and accurately determining the volume of a test liquid aliquot which can be used to calibrate a liquid delivery device. The method is particularly useful for determining the volume of an aliquot of a test liquid which is complex or non-aqueous, or is both complex and non-aqueous. The test-stock mixture contains at least the test liquid and a stock solution including a first dye, the first dye having absorbance characteristics which are measurably distinguishable from the absorbance characteristics of a second dye. The test-stock mixture is mixed with a diluent including the second dye to form a sample solution to be used to measure absorbances of the first dye and the second dye. The volume of the test-stock mixture aliquot is calculated by using a formula based on the Beer-Lambert law which incorporates the measured absorbance values and a dilution characteristic of the test-stock mixture. The test liquid and the stock solution are combined gravimetrically in a controlled ratio so that the flow characteristics of the test-stock mixture correspond to the flow characteristics of the test liquid and without affecting the ability to distinguish the absorbance characteristics between the first dye and the second dye.

Claims

1. A system to create a test-stock mixture to be used in the calibration of a liquid handling device, the test-stock mixture including a test liquid, the system comprising:

a. a stock solution including a first dye with a known absorbance characteristic; and

b. instructions for mixing the test liquid with the stock solution to form the test-stock mixture in a ratio of test liquid to stock solution sufficient so that the flow characteristics of the test-stock mixture correspond to the flow characteristics of the test liquid without affecting the ability to distinguish the absorbance characteristics between the first dye and a second dye, the second dye having a known absorbance characteristic different from the absorbance characteristic of the first dye.

2. The system of claim 1 wherein the instructions include gravimetrically measuring the mass ratio of the test liquid to the stock solution.

3. The system of claim 1 wherein the stock solution includes the second dye.

4. A method to create a test-stock mixture to be used in the determination of a volume of the test-stock mixture to be dispensed from a liquid handling device to be calibrated, the test-stock mixture including a test liquid of interest, the method comprising the step of mixing the test liquid with a stock solution, which stock solution includes a first dye with a known absorbance characteristic, to form the test-stock mixture in a ratio of test liquid to stock solution sufficient so that the flow characteristics of the test-stock mixture correspond to the flow characteristics of the test liquid without affecting the ability to distinguish the absorbance characteristics between the first dye and a second dye, the second dye having a known absorbance characteristic different from the absorbance characteristic of the first dye.

5. The method of claim 4 wherein the step of mixing includes the step of mixing the test liquid and the stock solution in a weight ratio as a function of the density of the stock solution and the density of the test liquid.

6. The method of claim 4 further comprising the step of calculating a dilution ratio of the stock solution.

7. The method of claim 6 further comprising the step of determining a z-correction factor for fluctuations in density values of the test liquid and the stock solution.

8. The method of claim 4 wherein the stock solution includes the second dye.

9. The method of claim 4 wherein the known absorbance characteristic of the first dye of the stock solution includes an absorbance per pathlength of the first dye, the method further comprising the step of determining a revised absorbance per pathlength of the first dye in the test-stock mixture.

10. The method of claim 4 wherein the known absorbance characteristic of the second dye includes an absorbance per pathlength of the second dye, the method further comprising the step of determining a revised absorbance per pathlength of the second dye in the test-stock mixture.

11. A method for determining the volume of a liquid aliquot to be dispensed from a handling device, comprising the steps of:

a. making a test-stock mixture by mixing a test liquid having a known weight and a known density value with a stock solution having a known weight and a known density value, the stock solution including a first dye with a known absorbance characteristic, wherein the known weight of the first stock solution and the known weight of the test liquid are selected in a ratio so that the flow characteristics of the test-stock mixture correspond to the flow characteristics of the test liquid without affecting the ability to distinguish the absorbance characteristics between the first dye and a second dye, the second dye having a known absorbance characteristic different from the absorbance characteristic of the first dye;

b. adding an aliquot of the test-stock mixture to a liquid holder;

c. adding a diluent to the test-stock mixture in the liquid holder to produce a sample solution, the diluent including the second dye only;

d. measuring the absorbance values of the first dye and the second dye in the sample solution at a first wavelength and a second wavelength; and

e. determining the volume of the test-stock mixture aliquot by using the measured absorbance values of the sample solution and the absorbance per pathlength of either or both of the first dye and second dye.

12. The method of claim 11 wherein the liquid holder is a multi-well plate.

13. The method of claim 11 wherein step (e) is performed by using computer-executable software stored on a computer-readable medium, the computer-executable software being capable of calculating volume of the test-stock mixture aliquot based upon absorbance values measured by using the method.

14. The method of claim 11 wherein the liquid holder is in the shape of a truncated cone and wherein the step of determining includes the step of calculating the volume of the aliquot by the equation

$V_S=\frac{\pi }{}$

·

D 2 4 ·

a λ

1 ·

( A λ

1 ) + π

·

D ·

tan ⁢

 

⁢

θ

2 ·

a λ

1 ·

a λ

2 ·

( A λ

1 ·

A λ

2 ) + π

·

tan ⁢

 

⁢

θ

3 ·

a λ

1 ·

a λ

2 2 ·

( A λ

1 ·

A λ

2 2 )

where (V_S) is the volume of the aliquot of test-stock mixture, D is the diameter of the liquid holder, O is the taper angle of the liquid holder, (A<sub>λ

1</sub>) is the measured absorbance of the first dye at the first wavelength, (A<sub>λ

2</sub>) is the measured absorbance of the second dye at the second wavelength, (α

<sub>λ

1</sub>) is the absorbance per unit pathlength of the first dye at the first wavelength, and (α

<sub>λ

2</sub>) is the absorbance per unit pathlength of the second dye at the second wavelength.

15. The method of claim 11 wherein the liquid holder is in the shape of a truncated square-based pyramid and wherein the step of determining includes the step of calculating the volume of the aliquot by the equation

$V_S=\frac{W_B}{a_{{\lambda }_{}}}$

1 ·

( A λ

1 ) + W B ·

( W T - W B ) h ·

a λ

1 ·

a λ

2 ⁢

 

·

( A λ

1 ·

A λ

2 ) + ( W T - W B ) 2 3 ·

h 2 ·

a λ

1 ·

a λ

2 2 ·

( A λ

1 ·

A λ

2 2 )

where (V_S) is the volume of the aliquot of test-stock mixture, (A<sub>λ

1</sub>) is the measured absorbance of the first dye at the first wavelength, (A<sub>λ

2</sub>) is the measured absorbance of the second dye at the second wavelength, (α

<sub>λ

1</sub>) is the absorbance per unit pathlength of the first dye at the first wavelength, (α

<sub>λ

2</sub>) is the absorbance per unit pathlength of the second dye at the second wavelength, (W_B) is the width of the bottom of the square well, (W_T) is the width of the top of the square well, and (h) is the height of the entire well.

16. An apparatus for determining the volume of a liquid solution to be dispensed from a handling device, the apparatus comprising:

a. an analytical balance;

b. a spectrophotometer;

c. a liquid holder;

d. a central processing unit; and

e. computer-executable software stored on a computer-readable medium, the computer-executable software being capable of calculating volume of a test-stock mixture aliquot by using the density values of a test liquid and a stock solution and by using absorbance values measured by carrying out a method, the method comprising the steps of.

i. making the test-stock mixture by mixing a known weight of the test liquid with a known weight of a stock solution including a first dye having a known absorbance characteristic which is measurably distinguishable from the known absorbance characteristic of a second dye,

ii. adding an aliquot of the test-stock mixture to a liquid holder;

iii. adding a diluent to the test-stock mixture in the liquid holder to produce a sample solution, the diluent including the second dye;

iv. measuring the absorbance values of the first dye and the second dye in the sample solution at a first wavelength and a second wavelength; and

v. calculating the volume of the test-stock mixture aliquot using the computer-executable software, the absorbance values, and the density values of the test liquid and the stock solution.

17. A kit for determining the volume of a test-stock mixture to be dispensed from a handling device, the test-stock mixture including a test liquid, wherein the test liquid is a complex and/or non-aqueous liquid, the kit comprising:

a. instructions for carrying out a method for determining the volume of a liquid aliquot, comprising the steps of;

i. making a test-stock mixture by mixing the test liquid having a known weight and a known density value with a stock solution having a known weight and a known density value, the stock solution including a first dye with a known absorbance characteristic different from a known absorbance characteristic of a second dye, wherein the known weight of the first stock solution and the known weight of the test liquid are selected in a ratio so that the flow characteristics of the test-stock mixture correspond to the flow characteristics of the test liquid without affecting the ability to distinguish the absorbance characteristics between the first dye and the second dye;

ii. adding an aliquot of the test-stock mixture to a liquid holder;

iii. adding a diluent to the test-stock mixture in the liquid holder to produce a sample solution, the diluent including the second dye;

iv. measuring the absorbance values of the first dye and the second dye in the sample solution at a first wavelength and a second wavelength; and

v. determining the volume of the test-stock mixture aliquot by using the measured absorbance values and the density values of the test liquid and the stock solution; and

b. the stock solution.

18. The kit of claim 17 wherein the kit includes a test-stock starter mixture including the test liquid and the stock solution in place of the stock solution, the test-stock starter solution including the test liquid and the stock solution in a known weight ratio.

19. The kit of claim 18 wherein the test-stock starter mixture is contained in a second liquid holder, wherein the second liquid holder is sealed to prevent gas exchange between the inside of the second liquid holder and the outside of the second liquid holder.

20. The kit of claim 17 including either or both of the first dye and the second dye in powder form, the kit further comprising instructions for making either or both of the stock solution and the diluent using selectable ones of the first dye and the second dye.

21. The kit of claim 17 wherein the liquid holder is a well of a multi-well plate.

22. The kit of claim 17 wherein the kit further includes the first dye.

23. The kit of claim 17 wherein the kit further includes more than one dye which may be used as the first dye.

24. The kit of claim 17 wherein the kit further includes the second dye.

25. The kit of claim 17 wherein the kit further includes more than one dye which may be used as the second dye.

26. The kit of claim 17 wherein the kit further contains computer-executable software stored on a computer-readable medium, the computer-executable software being capable of calculating volume of a liquid aliquot based upon absorbance values measured by carrying out the method and based upon the density of the test liquid.

27. The kit of claim 17 wherein the diluent is replaced with a test-diluent mixture, the test-diluent mixture including the test liquid and the diluent.

28. The kit of claim 17 wherein the kit further includes a test-diluent starter mixture including the test liquid and the diluent, the test-diluent starter solution including the test liquid and the diluent in a known weight ratio.

29. A system to create a test-diluent mixture to be used in the calibration of a liquid handling device, the test-diluent mixture including a test liquid, the system comprising:

a. a diluent including a first dye with a known absorbance characteristic; and

b. instructions for mixing the test liquid with the diluent to form the test-diluent mixture in a ratio of test liquid to diluent without affecting the ability to distinguish the absorbance characteristics between the first dye and a second dye, the second dye having a known absorbance characteristic different from the absorbance characteristic of the first dye.

30. The system of claim 29 further comprising a stock solution including the first dye, the stock solution for mixing with the test-diluent mixture to form a sample solution, wherein the sample solution is subject to measurement of the absorbance values of the first dye and the second dye.

31. The system of claim 29 further comprising a stock solution including the first dye and the second dye, the stock solution for mixing with the test-diluent mixture to form a sample solution, wherein the sample solution is subject to measurement of the absorbance values of the first dye and the second dye.

32. The system of claim 29 further comprising a test-stock mixture including the test liquid and a stock solution, the test-stock mixture including the first dye, the test-stock mixture for mixing with the test-diluent mixture to form a sample solution, wherein the sample solution is subject to measurement of the absorbance values of the first dye and the second dye.

33. The system of claim 29 further comprising a test-stock mixture including the test liquid and a stock solution, the test-stock mixture including the first dye and the second dye, the test-stock mixture for mixing with the test-diluent mixture to form a sample solution, wherein the sample solution is subject to measurement of the absorbance values of the first dye and the second dye.

34. A method for determining the volume of an aliquot of a liquid dispensed into a liquid holder, wherein the liquid is or forms part of a sample solution, wherein the sample solution includes a first dye and a second dye to be measured for absorbance at a first wavelength and a second wavelength, and wherein the liquid holder is in the shape of a truncated cone, the method comprising the steps of:

a. measuring the absorbance of the first dye and the second dye at the first wavelength and the second wavelength; and

b. calculating the volume of the aliquot of liquid in the liquid holder using the equation

$V_S=\frac{\mathrm{\pi <br><br>}·<br><br>D^2}{4·<br><br>a_{{\mathrm{\lambda <br><br>}}_1<br><br>\text{\hspace{1em}<br><br>}}}·<br><br>\left(A_{{\mathrm{\lambda <br><br>}}_1}\right)+\frac{\mathrm{\pi <br><br>}·<br><br>D·<br><br>\tan <br><br>\text{\hspace{1em}<br><br>}<br><br>\mathrm{\theta <br><br>}}{2·<br><br>a_{{\mathrm{\lambda <br><br>}}_1}·<br><br>a_{{\mathrm{\lambda <br><br>}}_2<br><br>\text{\hspace{1em}<br><br>}}}·<br><br>\left(A_{{\mathrm{\lambda <br><br>}}_1}·<br><br>A_{{\mathrm{\lambda <br><br>}}_2}\right)+\frac{\mathrm{\pi <br><br>}·<br><br>\tan <br><br>\text{\hspace{1em}<br><br>}<br><br>\mathrm{\theta <br><br>}}{3·<br><br>a_{{\mathrm{\lambda <br><br>}}_1}·<br><br>a_{{\mathrm{\lambda <br><br>}}_2}^2}·<br><br>\left(A_{{\mathrm{\lambda <br><br>}}_1}·<br><br>A_{{\mathrm{\lambda <br><br>}}_2}^2\right)$

where (V_S) is the volume of the aliquot of liquid, D is the diameter of the liquid holder, θ

is the taper angle of the liquid holder, (A<sub>λ

1</sub>) is the measured absorbance of the first dye at the first wavelength, (A<sub>λ

2</sub>) is the measured absorbance of the second dye at the second wavelength, (α

<sub>λ

1</sub>) is the absorbance per unit pathlength of the first dye at the first wavelength, and (α

<sub>λ

2</sub>) is the absorbance per unit pathlength of the second dye at the second wavelength.

35. A method for determining the volume of an aliquot of a liquid dispensed into a liquid holder, wherein the liquid is or forms part of a sample solution, wherein the sample solution includes a first dye and a second dye to be measured for absorbance at a first wavelength and a second wavelength, and wherein the liquid holder is in the shape of a truncated square-based pyramid, the method comprising the steps of:

a. measuring the absorbance of the first dye and the second dye at the first wavelength and the second wavelength; and

b. calculating the volume of the aliquot of liquid in the liquid holder using the equation

$V_S=\frac{V_B}{a_{{\mathrm{\lambda <br><br>}}_1}}·<br><br>\left(A_{{\mathrm{\lambda <br><br>}}_1}\right)+\frac{W_B·<br><br>\left(W_T-W_B\right)}{h·<br><br>a_{{\mathrm{\lambda <br><br>}}_1}·<br><br>a_{{\mathrm{\lambda <br><br>}}_2}}·<br><br>\left(A_{{\mathrm{\lambda <br><br>}}_1}·<br><br>A_{{\mathrm{\lambda <br><br>}}_2}\right)+\frac{{\left(W_T-W_B\right)}^2}{3·<br><br>h^2·<br><br>a_{{\mathrm{\lambda <br><br>}}_1}·<br><br>a_{{\mathrm{\lambda <br><br>}}_2}^2}·<br><br>\left(A_{{\mathrm{\lambda <br><br>}}_1}·<br><br>A_{{\mathrm{\lambda <br><br>}}_2}^2\right)$

where (V_S) is the volume of the aliquot of liquid, (A<sub>λ

1</sub>) is the measured absorbance of the first dye at the first wavelength, (A<sub>λ

2</sub>) is the measured absorbance of the second dye at the second wavelength, (α

<sub>λ

1</sub>) is the absorbance per unit pathlength of the first dye at the first wavelength, (α

<sub>λ

2</sub>) is the absorbance per unit pathlength of the second dye at the second wavelength, (W_B) is the width of the bottom of the square well, (W_T) is the width of the top of the square well, and (h) is the height of the entire well.