Method for sampling and measuring the content of a low-molecular weight compound in a complex fluid medium

• US 4,311,789 A
• Filed: 08/27/1979
• Issued: 01/19/1982
• Est. Priority Date: 12/31/1975
• Status: Expired due to Term

• Current Assignee: Gambro Lundia AB (Baxter International Inc.)
• Original Assignee: Gambro AG (Baxter International Inc.)
• Inventors: Nylen, Ulf T. G., Qvarnstrom, Lars A. G.
• Primary Examiner(s): Wiseman, Thomas
• Application Number:
  US06/069,698
• Time in Patent Office: 876 Days
• Field of Search: 210/22, 210/23, 210/321, 210/634, 210/635, 210/644, 210/645, 210/646, 210/647, 128/632, 128/630, 435/10, 435/12, 435/14, 435/18, 435/28, 435/287, 435/291, 422/50, 422/68, 422/81, 23/230 B, 424/2
• US Class Current: 435/10
• CPC Class Codes: A61B 5/14528 invasively
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/686 Permanently implanted devices, e.g. pacemakers, other stimulators, biochips A61B5/6861 takes precedence
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: B01D 61/244 comprising multiple dialysis steps
• CPC Class Codes: B01D 63/02 Hollow fibre modules
• CPC Class Codes: B01D 63/043 with separate tube sheets
• CPC Class Codes: C12N 11/14 Enzymes or microbial cells immobilised on or in an inorganic carrier
• CPC Class Codes: C12Q 1/26 involving oxidoreductase
• CPC Class Codes: C12Q 1/54 involving glucose or galactose
• CPC Class Codes: C12Q 1/58 involving urea or urease
• CPC Class Codes: C12Q 1/60 involving cholesterol
• CPC Class Codes: C12Q 1/62 involving uric acid
• CPC Class Codes: Y10T 436/255 including use of a solid sorbent, semipermeable membrane, or liquid extraction

Abstract

A method is provided for sampling and measuring the content of a low-molecular weight compound, such as glucose, cholesterol, or urea, in a complex fluid medium to be sampled, such as blood. A dialyzer is placed in contact with the complex fluid medium so that it passes through the dialyzer. One or more semipermeable membranes are disposed within the complex fluid medium to form one or more passageways for the passage of dialysis fluid, with the passageways being substantially smaller in volume than the volume of the surrounding complex fluid medium. A fractional portion of the complex fluid medium is acted on by the dialysis fluid and dialyzed so that only a fractional portion of the low-molecular weight compound diffuses into the passageways containing the dialysis fluid to produce a dialysate in the passageways. The dialysate is then measured to determine the content of the low-molecular weight compound in the complex fluid medium.

Claims

1. A method of sampling and measuring the content of a low molecular weight compound in a complex fluid medium to be sampled, comprising the steps of:

providing a complex fluid medium to be sampled;

arranging semi-permeable means in said complex fluid medium to be sampled so as to define one or more passageways in said complex fluid medium for the passage of dialysis fluid therethrough, said semi-permeable means being permeable to the low molecular weight compound in said complex fluid medium whose content is to be measured;

conducting dialysis fluid through said passageways defined by said semi-permeable means in said complex fluid medium, said semi-permeable means being sized so that only a fractional portion of the volume of said complex fluid medium surrounding said semi-permeable means is dialyzed by said dialysis fluid being conducted through said passageways whereby a portion of the low molecular weight compound in said complex fluid medium diffuses into said passageways containing said dialysis fluid to thereby produce a dialysate in said passageways;

maintaining the pressure of said dialysis fluid within said passageways higher than the pressure of said complex fluid medium to substantially reduce ultrafiltration from said complex fluid medium to said dialysis fluid; and

measuring a property of said produced dialysate which is related to the content of the low molecular weight compound in said dialysate to determine the content of the low molecular weight compound in said complex fluid medium.

2. The method of claim 1 wherein said step of arranging semi-permeable means in said complex fluid medium comprises the step of placing one or more semi-permeable membranes directly in said complex fluid medium.

3. The method of claim 2 wherein the complex fluid medium is blood of a patient, and wherein the step of arranging one or more semi-permeable membranes comprises arranging one or more semi-permeable membranes in a blood vessel of the patient.

4. The method of claim 1 wherein the step of measuring comprises making a first measurement of a predetermined property of said dialysate;

adding an enzyme to said dialysate to chemically react with said low-molecular weight compound in said dialysate to produce a change in said predetermined property of said dialysate which can be measured, and making a second measurement of said predetermined property in said changed, enzyme reacted dialysate.

5. The method of claim 4 wherein the step of measuring includes measuring the temperature change produced by said eyzymatic chemical reaction.

6. The method of claim 1 wherein the step of measuring is carried out while at least one of the pressure and the temperature in said dialyzer is kept constant.

7. The method of claim 5 wherein the step of measuring is carried out while at least one of the pressure and the temperature at the measuring point is kept constant.

8. The method of claim 1 wherein the step of measuring comprises chemically reacting said dialysate with an enzyme and then measuring a property of said enzyme reacted dialysate.

9. The method of claim 1 wherein said low-molecular weight compound is glucose, and said enzyme is glucose oxidase.

10. The method of claim 8 wherein said low-molecular weight compound is glucose, and said enzyme is hexokinase and adenosine triphosphate (ATP).

11. The method of claim 8 wherein said low-molecular weight compound is penicillin, and said enzyme is penicillinase.

12. The method of claim 8 wherein said low-molecular weight compound is cholesterol, and said enzyme is cholesterol oxidase.

13. The method of claim 8 wherein said low-molecular weight compound is urea, and said enzyme is urease.

14. The method of claim 8 wherein said low-molecular weight compound is uric acid, and said enzyme is uricase.

15. The method of claim 1 further including the step of returning said complex fluid medium, after dialysis, to the source of said complex fluid medium.

16. The method of claim 1 further including the step of diluting said dialysate with water, buffer, or reagent solution before measuring said dialysate.

17. The method of claim 1 further including the step of evaluating the results of said measuring step to treat said complex medium.

18. The method of claim 1 wherein the step of arranging semi-permeable means in said complex fluid medium to be sampled comprises arranging one or more semi-permeable membranes in said complex fluid medium to be sampled to form therein said one or more passageways for the passage of dialysis fluid therethrough.

19. The method of claim 18 further including the step of coating said semipermeable membrane with anticoagulant to prevent disturbances with the complex fluid medium.

20. The method of claim 18 wherein the volume of said passageways formed by said semi-permeable membranes is substantially smaller than the volume of said complex fluid medium surrounding said passageways.

21. The method of claim 20 wherein said dialyzer includes at least two semipermeable membranes, and said dialysis fluid is supplied to each of said membranes so that the flow through each is independent of the other.

22. The method of claim 1 wherein the step of arranging semi-permeable means in the complex fluid medium comprises providing a dialyzer having said semi-permeable means therein for forming said one or more passageways in said dialyzer for the passage of dialysis fluid therethrough, and connecting said dialyzer with said complex fluid medium to be sampled so that said complex fluid medium is conducted through said dialyzer along said semi-permeable means therein.