Method for Preparation of Liquid Mixtures

Patent metadata

Field	Value
Publication number	US-2020240884-A1
Application number	US-202016804440-A
Country	US
Kind code	A1
Filing date	Feb 28, 2020
Priority date	Sep 30, 2013
Publication date	Jul 30, 2020
Grant date	—

Abstract

The present invention relates to the preparation of liquid mixtures, and more particularly to the preparation of a liquid mixture, such as a buffer, wherein the conductivity of the liquid mixture is measured and the pH indirectly determined if the buffer concentration is known. Another object of the present invention is to provide a method of preparing a liquid mixture with a predetermined pH value by using conductivity as feedback control parameter.

First claim

1 . A buffer system comprising,
a. measuring conductivity of a buffer using a conductivity sensor; b. measuring or calculating concentration of the buffer; and c. adding controlled amounts of buffer components to said buffer based on the measured conductivity and the measured or calculated concentration of the buffer to maintain buffer concentration constant until a specific conductivity value is obtained,
wherein said specific conductivity value is correlated to a predetermined pH value and the buffer concentration by a surface model, comprising using a training data set with known concentrations, specific conductivities and pHs obtained from a training set of buffer systems; and measuring the pH for the solutions belonging to the training data set and using a numerical regression method to obtain the surface model equation as a regression model from the training data.

2 . The system of claim 1 , wherein the buffer is an acetate buffer, a citrate buffer, a phosphate buffer, or a Tris buffer.

3 . The system of claim 1 , wherein the surface model equation is of the form:
pH= A+B* concentration of the buffer+ C* concentration of the buffer {circumflex over ( )}2+ D* specific conductivity; and
wherein A, B, C, and D are buffer specific constants determined through the regression modelling of the training data.

4 . The system of claim 1 , wherein the surface model equation is of the form;
pH= A+B* concentration of the buffer+ C* concentration of the buffer {circumflex over ( )}2+ D* specific conductivity+ E* specific conductivity{circumflex over ( )}2; and
wherein A, B, C, D, and E are buffer specific constants determined through the regression modelling of the training data.

5 . The system of claim 1 , wherein the concentration of the buffer is measured by any of Index of Refraction (IoR), Infrared Red (IR), and Ultraviolet (UV) absorbance at several wavelengths.

6 . The system of claim 1 , wherein the concentration of the buffer is calculated from the known flows from stock solutions of known concentrations and the flows of other components like water and non-buffering salts or additives to the point of mixture of the buffer.

7 . The system of claim 1 , wherein the concentration of the buffer is calculated from the measured conductivities, IR values, or IoR values and known flows from stock solutions and the flows of other components like water and non-buffering salts or additives to the point of mixture of the buffer.

8 . The system of claim 1 , which is computer-implemented.

9 . A method for controlling a buffer formulation, the method comprising using the buffer system of claim 1 .

10 . A method for controlling an in-line dilution system, the method comprising using the buffer system of claim 1 .

11 . A method for screening experiments wherein pH and the concentration of a buffer is used as a design of experiment (DoE) parameter, the method comprising using the buffer system of claim 1 .

12 . A device comprising a computer and a computer program product comprising instructions for causing the computer to perform a method of preparing a buffer having a predetermined pH value, the method comprising,
a. measuring conductivity of a buffer using a conductivity sensor; b. measuring or calculating concentration of the buffer; and c. adding controlled amounts of buffer components to said buffer based on the measured conductivity and the measured or calculated concentration of the buffer to maintain buffer concentration constant until a specific conductivity value is obtained,
wherein said specific conductivity value is correlated to a predetermined pH value and the buffer concentration by a surface model, comprising using a training data set with known concentrations, specific conductivities and pHs obtained from a training set of buffer systems; and measuring the pH for the solutions belonging to the training data set and using a numerical regression method to obtain the surface model equation as a regression model from the training data.

13 . The device of claim 12 , further comprising a conductivity sensor and a concentration sensor and the computer for calculating pH from measured conductivity.

14 . The device of claim 12 , further comprising a conductivity sensor and allowing input of buffer concentration and the computer for calculating pH from measured conductivity.

Assignees

• Ge Healthcare Bio Sciences Ab

Inventors

• Carredano Enrique Napoleon
• Strandberg Elenor

Classifications

• G05D21/02 Primary

  characterised by the use of electric means · CPC title

• B01J47/15

  for obtaining a solution having a fixed pH · CPC title

• G01N21/41

  Refractivity; Phase-affecting properties, e.g. optical path length (G01N21/21 takes precedence) · CPC title

• G01N27/06

  of a liquid (involving electrolysis G01N27/26) · CPC title

• G01N21/33

  using ultraviolet light (G01N21/39 takes precedence) · CPC title