Innovation to assay mixing

• US 9,766,213 B2
• Filed: 10/02/2014
• Issued: 09/19/2017
• Est. Priority Date: 10/02/2013
• Status: Active Grant

• Current Assignee: Bio-Rad Laboratories Incorporated
• Original Assignee: Bio-Rad Laboratories Incorporated
• Inventors: Berkelman, Tom R., Harbers, Adriana Jeanne, Hilario, Jovencio, Urban, Michael Keith
• Primary Examiner(s): LARKIN, DANIEL SEAN
• Application Number:
  US14/505,227
• Publication Number:
  US 20150090343A1
• Time in Patent Office: 1,083 Days
• Field of Search: 73 101, 73 102, 73 1, 73 3, 356433, 137 2
• CPC Class Codes: G01N 30/04 Preparation or injection of sample to be analysed
• CPC Class Codes: G01N 30/26 Conditioning of the fluid carrier; Flow patterns
• CPC Class Codes: G01N 30/8665 for calibrating the measuring apparatus
• CPC Class Codes: Y10T 137/0324 With control of flow by a condition or characteristic of a fluid

Abstract

Methods, articles of manufacture, and kits for calibrating fluid delivery systems are provided. A fluid delivery system connected to N input streams, where N is an integer greater than or equal to 2, mixes together fluid from the N input streams to form an output stream. The methods involve obtaining N test solutions, each containing a dye, providing optical absorbances of the test solutions at appropriate wavelengths, injecting the test solutions into the input streams, mixing the test solutions, and measuring the absorbance of the output stream at the same wavelengths. The methods also involve comparing the absorbances of the test solutions with the absorbances of the output stream, which can include calculating ratios and comparing the ratios with target values. The methods can further involve adjusting operation of the fluid delivery system based upon the absorbances. In some embodiments, the dyes have largely non-overlapping absorbance spectra.

Claims

1. A method of calibrating a fluid delivery system, the method comprising:

providing a fluid delivery system connected to N input streams, wherein N is an integer greater than or equal to two, and wherein the fluid delivery system mixes together fluids from the N input streams to form an output stream;

obtaining N test solutions, wherein each test solution comprises a dye having a characteristic wavelength of maximum absorbance (λ

_max);

for each of the N test solutions,

designating a wavelength λ

_test, wherein λ

_test is within the range from 90% of λ

_max to 110% of λ

_max, and

providing an input absorbance of the test solution, the input absorbance being the absorbance of the solution at λ

_test;

injecting the N test solutions into the N input streams;

mixing the N test solutions in the fluid delivery system;

measuring the absorbance of the output stream at N wavelengths, the wavelengths being the λ

_tests designated for the test solutions, thereby obtaining an output absorbance for each test solution; and

comparing the input absorbance with the output absorbance for each test solution, thereby calibrating the fluid delivery system.

2. A method of iteratively calibrating a fluid delivery system, the method comprising:

providing a fluid delivery system connected to N input streams, wherein N is an integer greater than or equal to two and wherein the fluid delivery system mixes together fluids from the N input streams to form an output stream;

providing N test solutions;

designating a target portion for at least one test solution in the output stream;

calibrating the fluid delivery system a first time according to claim 1;

adjusting operation of the fluid delivery system based upon the input absorbance and the output absorbance of the at least one test solution, and the target portion of the at least one test solution in the output stream;

calibrating the fluid delivery system a second time according to claim 1; and

further adjusting operation of the fluid delivery system based upon the change in the output absorbance of the at least one test solution between calibrating the fluid delivery system the first time and calibrating the fluid delivery system the second time.

3. The method of claim 2, wherein λ

_max of the dye of any first test solution differs from λ

_max of the dye of any second test solution by at least 50, 100, 200, or 300 nm.

4. The method of claim 2, wherein the λ

_test designated for any first test solution differs from the λ

_test designated for any second test solution by at least 50, 100, 200, or 300 nm.

5. The method of claim 2, wherein the absorbance of any first test solution at the λ

_max of the dye of the first test solution is at least 10 times greater than the absorbance of any second test solution at the same λ

_max.

6. The method of claim 2, wherein the absorbance of any particular test solution at the λ

_max of the dye of the particular test solution is at least 10 times greater than the sum of the absorbances of the remaining test solutions at the same λ

_max.

7. The method of claim 2, wherein the dyes of the test solutions are sulfonated aromatic dyes.

8. The method of claim 7, wherein the dyes of the test solutions are selected from the group consisting of pyrenes, boron-dipyrromethenes (BODIPYs), rhodamines, and indocyanines.

9. The method of claim 7, wherein the dyes of the test solutions are selected from the group consisting of MPTS, pyrromethene 556, sulforhodamine 101, and cardiogreen.

10. The method of claim 2, wherein the fluid delivery system comprises a valve associated with at least two input streams.

11. The method of claim 10, wherein the valve is associated with all N input streams.

12. The method of claim 2, further comprising adjusting the operation of the fluid delivery system based upon the input absorbance and the output absorbance of at least one test solution.

13. The method of claim 2, wherein said comparing comprises, for each test solution, dividing the output absorbance by the input absorbance to obtain a ratio, said ratio providing an estimate of the portion of the output stream comprising the test solution.

14. The method of claim 13, wherein the ratios for the N test solutions are all at least 0.001.

15. The method of claim 13, further comprising:

for each test solution,

designating a target portion for the test solution in the output stream, and

comparing the ratio with the target portion;

and wherein said mixing occurs according to the target portions for the test solutions.

16. The method of claim 15, wherein the target portions for the N test solutions are all at least 0.001.

17. The method of claim 15, further comprising adjusting the operation of the fluid delivery system based upon the ratio and the target portion for at least one of the test solutions.

18. The method of claim 17, wherein said adjusting comprises reducing the difference between the ratio and the target portion for at least one of the test solutions.