Device and method for determination of an analyte in blood

• US 9,347,958 B2
• Filed: 06/27/2014
• Issued: 05/24/2016
• Est. Priority Date: 06/27/2014
• Status: Active Grant

• Current Assignee: Hemocue AB (Danaher Corporation)
• Original Assignee: Hemocue AB (Danaher Corporation)
• Inventors: Jonsson, Malin, Riabova, Ekaterina, Eriksson, Hakan, Folkesson, Johan
• Primary Examiner(s): Shen, Bin
• Application Number:
  US14/317,558
• Publication Number:
  US 20150377913A1
• Time in Patent Office: 697 Days
• US Class Current: 1/1
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0803 Disc shape
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: C12Q 1/60 involving cholesterol
• CPC Class Codes: G01N 21/07 Centrifugal type cuvettes G01N21/09 takes precedence
• CPC Class Codes: G01N 21/78 producing a change of colour
• CPC Class Codes: G01N 2201/022 Casings
• CPC Class Codes: G01N 2333/775 Apolipopeptides
• CPC Class Codes: G01N 33/92 involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743

Abstract

A sample acquiring device, an apparatus and a method for spectrophotometric measurement of high density lipoprotein (HDL) and at least one of total cholesterol (TC), triglycerides (TG) and glucose (FPG).

Claims

1. A sample acquiring device comprising:

at least one inlet for receiving a body fluid sample,

at least one capillary sample reception cavity in capillary communication with said at least one inlet,

a first pathway in communication with said at least one inlet and a first measurement cavity, and

a second pathway in communication with said at least one inlet and a second measurement cavity, the second measurement cavity being separate from said first measurement cavity,

wherein the first pathway and the second pathway are in communication with said at least one capillary sample reception cavity such that spontaneous flow from the capillary sample reception cavity is prevented and such that body fluid sample is forcible from the capillary sample reception cavity into a first centrifugation cavity of said first pathway and a first centrifugation cavity of said second pathway by subjecting the sample acquiring device to a first centrifugation,

wherein said first centrifugation cavity of said first pathway is in capillary communication with a first capillary cavity of said first pathway and said first centrifugation cavity of said second pathway is in capillary communication with a first capillary cavity of said second pathway, such that at least a fraction of said body fluid sample in said first centrifugation cavity is transferable from said first centrifugation cavities to said first capillary cavities,

wherein, each of the first centrifugation cavities of the first pathway and of the second pathway has a lower portion and an upper portion oriented relative each other such that centrifugation of the sample acquiring device forces any sample in the first centrifugation cavity towards the lower portion,

wherein the first capillary cavity of the first pathway is in capillary communication only with the upper portion of the first centrifugation cavity of the first pathway,

wherein the first capillary cavity of the second pathway is in capillary communication only with the upper portion of the first centrifugation cavity of the second pathway,

wherein a precipitation agent is provided in said first capillary cavity of said second pathway,

wherein said first capillary cavity of said first pathway is in communication with a second centrifugation cavity of said first pathway and said first capillary cavity of said second pathway is in communication with a second centrifugation cavity of said second pathway, such that spontaneous flow from said first capillary cavities is prevented and such that said at least a fraction of said body fluid sample from the first capillary cavities is forcible from the said first capillary cavity of said first pathway and into a second centrifugation cavity of said first pathway and from said first capillary cavity of said second pathway to a second centrifugation cavity of said second pathway by subjecting the sample acquiring device to a second centrifugation,

wherein said second centrifugation cavity of said first pathway is in capillary communication with a second capillary cavity of said first pathway and said second centrifugation cavity of said second pathway is in capillary communication with a second capillary cavity of said second pathway, such that at least a fraction of said body fluid sample in said second centrifugation cavities is transferable from said second centrifugation cavities to said second capillary cavities,

wherein said second capillary cavity of said first pathway is in communication with a transfer cavity of said first pathway and said second capillary cavity of said second pathway is in communication with a transfer cavity of said second pathway, such that spontaneous flow from said second capillary cavities is prevented and such that at least a fraction of said body fluid sample in said second capillary cavities is forcible from said second capillary cavity of said first pathway into said first measurement cavity via said transfer cavity of said first pathway and from said second capillary cavity of said second pathway into said second measurement cavity via said transfer cavity of said second pathway by subjecting the sample acquiring device to a third centrifugation,

wherein at least one chromophore is provided in said second capillary cavity, in said transfer cavity or in said first measurement cavity of said first pathway, and

wherein at least one chromophore is provided in said second capillary cavity, in said transfer cavity or in said second measurement cavity of said second pathway.

2. A sample acquiring device according to claim 1, wherein said precipitation agent comprises non-HDL lipoprotein complexing agents, preferably selected from the group consisting of dextran sulfate and a salt of a divalent metal ion, chosen from Ca2+ and Mg2+, preferably magnesium chloride (MgCl2);

terephthalate (PTA) and a divalent metal ion, such as Ca2+ and Mg2+, preferably magnesium chloride (MgCl2); and

polyethylene glycol (PEG) 6000, dextran sulfate 50,000, sodium chloride (NaCl) and a salt of a divalent metal ion, chosen from Ca2+ and Mg2+, preferably magnesium chloride (MgCl2).

3. A sample acquiring device according to claim 1, wherein cholesterol esterase (CE);

cholesterol dehydrogenase (CDH);

at least one coenzyme selected from the group consisting of β

-nicotinamide adenine dinucleotide sodium salt (NAD+), NADP, thio-NAD+, thio-NADP, nicotinamide-purine dinucleotide, nicotinamide-methylpurine dinucleotide and nicotinamide-2-chloro-methylpurine dinucleotide; and

at least one substance selected from the group consisting of diaphorase, phenazine methosulfate, phenazine ethosulfate, phenazine phenosulfate and Meldola blue;

are provided in one or more of said second capillary cavity, said transfer cavity and said second measurement cavity of said second pathway.

4. A sample acquiring device according to claim 1, wherein cholesterol esterase (CE);

cholesterol dehydrogenase (CDH);

at least one coenzyme selected from the group consisting of β

-nicotinamide adenine dinucleotide sodium salt (NAD+), NADP, thio-NAD+, thio-NADP, nicotinamide-purine dinucleotide, nicotinamide-methylpurine dinucleotide and nicotinamide-2-chloro-methylpurine dinucleotide; and

at least one substance selected from the group consisting of diaphorase, phenazine methosulfate, phenazine ethosulfate, phenazine phenosulfate and Meldola blue;

are provided in said second capillary cavity of said second pathway.

5. A sample acquiring device according to claim 1, wherein said chromophore of said first pathway and said chromophore of said second pathway are redox indicator dyes.

6. A sample acquiring device according to claim 1, wherein a buffer agent is provided in said first capillary cavity of said first pathway.

7. A sample acquiring device according to claim 6, wherein the buffer agent is selected from the group consisting of buffer agents providing a pH within the range of 8-11 preferably from the group consisting of tris(hydroxymethyl)aminomethane (TRIS), glycine and potassium phosphate.

8. A sample acquiring device according to claim 7, wherein the buffer agent is selected from the group consisting of buffer agents providing a pH within the range of 10-11, and preferably the buffer agent is glycine.

9. A sample acquiring device according to claim 1,

wherein lipase;

glycerol dehydrogenase (GYDH);

at least one coenzyme selected from the group consisting of β

-nicotinamide adenine dinucleotide sodium salt (NAD+), NADP, thio-NAD+, thio-NADP, nicotinamide-purine dinucleotide, nicotinamide-methylpurine dinucleotide and nicotinamide-2-chloro-methylpurine dinucleotide; and

at least one substance selected from the group consisting of diaphorase, phenazine methosulfate, phenazine ethosulfate, phenazine phenosulfate and Meldola blue;

are provided in one or more cavities of said first pathway,

wherein said one or more cavities is selected from the group consisting of said first capillary cavity, said second centrifugation cavity, said second capillary cavity, said transfer cavity, and said first measurement cavity of said first pathway, and

wherein lipase and GYDH are provided in separate cavities.

10. A sample acquiring device according to claim 9, wherein said one or more cavities is selected from the group consisting of said first capillary cavity and said second capillary cavity of said first pathway.

11. A sample acquiring device according to claim 7, wherein the buffer agent is selected from the group consisting of buffer agents providing a pH within the range of 8-10, and preferably the buffer agent is tris(hydroxymethyl)aminomethane (TRIS).

12. A sample acquiring device according to claim 1, wherein cholesterol esterase (CE);

cholesterol dehydrogenase (CDH);

at least one coenzyme selected from the group consisting of β

-nicotinamide adenine dinucleotide sodium salt (NAD+), NADP, thio-NAD+, thio-NADP, nicotinamide-purine dinucleotide, nicotinamide-methylpurine dinucleotide and nicotinamide-2-chloro-methylpurine dinucleotide; and

at least one substance selected from the group consisting of diaphorase, phenazine methosulfate, phenazine ethosulfate, phenazine phenosulfate and Meldola blue;

are provided in one or more of cavities of said first pathway, and wherein said one or more cavities is selected from the group consisting of said first capillary cavity, said second centrifugation cavity, said second capillary cavity, said transfer cavity, and said first measurement cavity of said first pathway.

13. A sample acquiring device according to claim 12, wherein said one or more cavities is selected from the group consisting of said first capillary cavity and said second capillary cavity of said first pathway.

14. A sample acquiring device according to claim 1,

wherein the second centrifugation cavity of the second pathway has a lower portion and an upper portion oriented relative each other such that a centrifugation of the sample acquiring device will force any sample in the second centrifugation cavity towards the lower portion, and

wherein the second capillary cavity of the second pathway is in capillary communication only with the upper portion of the second centrifugation cavity of the second pathway.

15. A sample acquiring device according to claim 1,

wherein the second centrifugation cavity of the first pathway has a lower portion and an upper portion oriented relative each other such that a centrifugation of the sample acquiring device will force any sample in the second centrifugation cavity towards the lower portion, and

wherein the second capillary cavity of the first pathway is in capillary communication only with the upper portion of the second centrifugation cavity of the first pathway.

16. An apparatus for spectrophotometric measurements of high density lipoprotein (HDL) and at least one of total cholesterol and triglycerides,

wherein the apparatus has a rotatable disc adapted to be rotated by an electrical motor according to a predetermined cycle,

wherein the rotatable disc has a cuvette receiving cavity adapted for receiving the sample acquiring device according to claim 1, said cuvette receiving cavity being located off center on said rotatable disc, and

wherein said apparatus has optical measurement units adapted for spectrophotometric measurements of at least said first and second measurement cavity of said sample acquiring device.

17. A sample acquiring device according to claim 1, wherein the first pathway and the second pathway are discrete relative to each other.