Automated analyzer with low-pressure in-line filtration

• US 8,733,152 B2
• Filed: 01/14/2011
• Issued: 05/27/2014
• Est. Priority Date: 01/19/2010
• Status: Active Grant

• Current Assignee: Bio-Rad Laboratories Incorporated
• Original Assignee: Bio-Rad Laboratories Incorporated
• Inventors: Likuski, Robert, Bartling, Donald, Kunquan, Yao, Le, Tong, Matsumoto, Kent
• Primary Examiner(s): Williams, Hezron E
• Assistant Examiner(s): KOLB, NATHANIEL J
• Application Number:
  US13/007,284
• Publication Number:
  US 20120103074A1
• Time in Patent Office: 1,229 Days
• Field of Search: 73/615.5, 73/615.6, 73/645.6, 436/161
• US Class Current: 73/61.56
• CPC Class Codes: G01N 2030/8813 biological materials
• CPC Class Codes: G01N 2035/0437 Cleaning cuvettes or reaction vessels
• CPC Class Codes: G01N 30/20 using a sampling valve
• CPC Class Codes: G01N 30/24 Automatic injection systems
• CPC Class Codes: G01N 30/40 using back flushing
• CPC Class Codes: G01N 35/1004 Cleaning sample transfer devices
• CPC Class Codes: G01N 35/1097 characterised by the valves valves in general F16K

Abstract

An automated analyzer for biological samples that contain particulate matter is adapted to be able to process a large number of samples without changing the analytical cartridge, and in many cases without changing the internal switching valves, by including a filter in the low-pressure section of the analyzer, and preferably configuring the analyzer to be able to perform backflushing on the filter between sample injections.

Claims

1. An automated analyzer comprising:

a low-pressure section comprising means for introducing sample to said analyzer, a sample dilution well for receiving a sample dilution fluid, and a low-pressure pump,

a high-pressure section comprising a high-pressure pump,

an analytical section comprising a sample loop and an analytical cartridge,

a switching valve for switching between (i) connecting said low-pressure section to said sample loop of said analytical section and (ii) connecting said high-pressure section to said sample loop of said analytical section,

a sample filter positioned in said low-pressure section, and

a backflush pump arranged to back flush the sample filter at low pressure with a wash fluid, wherein the sample dilution fluid and the wash fluid are composed of the same solution.

2. The automated analyzer of claim 1 wherein the low-pressure section comprises means for producing pressure pulsations in said sample filter.

3. The automated analyzer of claim 1 wherein the low-pressure section comprises an ultrasonic transducer for producing ultrasonic pressure waves in said sample filter.

4. The automated analyzer of claim 1, further comprising a backflush pump, and wherein said switching valve further comprises (iii) a third position connecting said backflush pump with a sample loop at low pressure.

5. The automated analyzer of claim 1, wherein the backflush pump is arranged to back flush the sample loop and the sample filter.

6. The automated analyzer of claim 1, wherein the apparatus comprises a sample dilution subsystem in the low pressure section and no valves are present between the filter and the sample dilution subsystem.

7. An automated analyzer comprising:

a sample dilution well,

a sample transfer subsystem comprising (i) a needle mounted on a mobile needle arm movable into a position whereby said needle is in fluid communication with said sample dilution well, (ii) a pump arranged to cause fluid to pass through said needle, and (iii) a two-way switching valve switchable between communicating said pump with said needle and communicating said pump with a source of wash fluid,

a sample loop and an analytical cartridge arranged to receive fluid emerging from said sample loop,

a low-pressure pump subsystem arranged to pump diluted sample from said sample dilution well to said sample loop at a low pressure of from about 1 psi to about 30 psi,

a high-pressure pump subsystem arranged to pump buffer liquid from a source of buffer liquid through said sample loop and said analytical cartridge at a high pressure of from about 1,000 psi to about 10,000 psi,

a multi-position switching valve having positions comprising (i) a first position connecting said low-pressure pump subsystem with said sample dilution well and said sample loop and thereby arranged to introduce diluted sample from said sample dilution well into said sample loop at said low pressure, and (ii) a second position connecting said high-pressure pump subsystem to said sample loop and said analytical cartridge and thereby arranged to direct diluted sample from said sample loop through said analytical cartridge at said high pressure, and

a sample filter positioned between said sample dilution well and said sample loop at a site maintained at said low pressure by said low-pressure pump subsystem at both of positions (i) and (ii) of said multi-position switching valve, and

a backflush pump arranged to back flush the sample filter at low pressure.

8. The automated analyzer of claim 7 wherein said sample dilution well has an outlet and said sample filter is positioned between said outlet and all switching valves of said analyzer.

9. The automated analyzer of claim 7 wherein said sample filter comprises a mesh screen.

10. The automated analyzer of claim 7 wherein said sample filter comprises a silver membrane.

11. The automated analyzer of claim 7 wherein said sample filter comprises a nylon membrane.

12. The automated analyzer of claim 7 wherein said sample filter comprises pores of 0.1 micron to 0.8 micron in width.

13. The automated analyzer of claim 7 wherein said pump is a syringe pump operable to cause fluid to pass through said needle in either direction.

14. The automated analyzer of claim 7 wherein said low-pressure pump subsystem comprises a syringe pump operable to both draw fluid into an interior of said syringe pump and to expel fluid from said interior.

15. The automated analyzer of claim 7 wherein said multi-position switching valve positions further comprise (iii) a third position connecting said backflush pump with said source of wash fluid and said sample filter and thereby arranged to backflush said sample filter with wash fluid from said source of wash fluid at said low pressure.

16. The automated analyzer of claim 15 wherein said low-pressure pump subsystem comprises a low-pressure pump, and a common pump serves as both said low-pressure pump and said backflush pump.

17. The automated analyzer of claim 15 further comprising pressure means for producing pressure pulsations on said wash fluid passing through said sample filter.

18. The automated analyzer of claim 15 further comprising means for producing ultrasonic pressure waves in said wash fluid passing through said sample filter.

19. The automated analyzer of claim 7, wherein the backflush pump is arranged to back flush the sample loop and the sample filter.

20. A method for analyzing a sample of biological fluid by column chromatography, said method comprising:

(A) introducing said sample into a low-pressure section of an automated analyzer, wherein said low-pressure section comprises a low-pressure pump and a sample dilution well for receiving a sample dilution fluid and said automated analyzer further comprises;

a high-pressure section comprising a high-pressure pump,

an analytical section comprising a sample loop and an analytical cartridge,

a switching valve for switching between position (i) connecting said low-pressure section to said sample loop of said analytical section and position (ii) connecting said high-pressure section to said sample loop of said analytical section while closing off said low-pressure section from said analytical section,

a sample filter positioned in said low-pressure section, and

a backflush pump arranged to back flush the sample filter at low pressure with a wash fluid, wherein the sample dilution fluid and the wash fluid are composed of the same solution;

(B) by way of said low-pressure pump, pumping said sample through said sample filter and into said sample loop with said switching valve in position (i); and

(C) by way of said high-pressure pump, pumping said sample from said sample loop through said analytical cartridge with said switching valve in position (ii); and

(D) detecting components of said sample separated from each other by said analytical cartridge.

21. The method of claim 20 further comprising backflushing said sample filter following step (D).

22. The method of claim 21 further comprising applying pressure pulsations to said sample filter during said backflushing or applying ultrasound vibrations to said sample filter during said backflushing.

23. An automated analyzer comprising:

a low-pressure section comprising means for introducing sample to said analyzer, a sample dilution well for receiving a sample dilution fluid, and a low-pressure pump,

a high-pressure section comprising a high-pressure pump,

an analytical section comprising a sample loop and an analytical cartridge,

switching means for switching between (i) connecting said low-pressure section to said sample loop of said analytical section and (ii) connecting said high-pressure section to said sample loop of said analytical section,

a sample filter positioned in said low-pressure section and no valve exists between the sample dilution well and the filter, and

a backflush pump arranged to back flush the sample filter at low pressure.

24. An automated analyzer comprising:

a sample dilution well,

a sample transfer subsystem comprising (i) a needle mounted on a mobile needle arm movable into a position whereby said needle is in fluid communication with said sample dilution well, (ii) pump means arranged to cause fluid to pass through said needle, and (iii) a two-way switching valve switchable between communicating said pump means with said needle and communicating said pump means with a source of wash fluid,

a sample loop and an analytical cartridge arranged to receive fluid emerging from said sample loop,

a low-pressure pump subsystem arranged to pump diluted sample from said sample dilution well to said sample loop at a low pressure of from about 1 psi to about 30 psi,

a high-pressure pump subsystem arranged to pump buffer liquid from a source of buffer liquid through said sample loop and said analytical cartridge at a high pressure of from about 1,000 psi to about 10,000 psi,

a multi-position switching valve having positions comprising (i) a first position connecting said low-pressure pump subsystem with said sample dilution well and said sample loop and thereby arranged to introduce diluted sample from said sample dilution well into said sample loop at said low pressure, and (ii) a second position connecting said high-pressure pump subsystem to said sample loop and said analytical cartridge and thereby arranged to direct diluted sample from said sample loop through said analytical cartridge at said high pressure,

a sample filter positioned between said sample dilution well and said sample loop at a site maintained at said low pressure by said low-pressure pump subsystem at both of positions (i) and (ii) of said multi-position switching valve section and wherein no valve exists between the sample dilution well and the filter, and

a backflush pump arranged to back flush the sample filter at low pressure.

25. A method for analyzing a sample of biological fluid by column chromatography, said method comprising:

(A) introducing said sample into a low-pressure section of an automated analyzer, wherein said low-pressure section comprises a low-pressure pump and a sample dilution well for receiving a sample dilution fluid and said automated analyzer further comprises;

a high-pressure section comprising a high-pressure pump,

an analytical section comprising a sample loop and an analytical cartridge,

a switching valve for switching between position (i) connecting said low-pressure section to said sample loop of said analytical section and position (ii) connecting said high-pressure section to said sample loop of said analytical section while closing off said low-pressure section from said analytical section,

a sample filter positioned in said low-pressure section wherein no valve exists between the sample dilution well and the filter, and

a backflush pump arranged to back flush the sample filter at low pressure;

(B) by way of said low-pressure pump, pumping said sample through said sample filter and into said sample loop with said switching valve in position (i); and

(C) by way of said high-pressure pump, pumping said sample from said sample loop through said analytical cartridge with said switching valve in position (ii); and

(D) detecting components of said sample separated from each other by said analytical cartridge.

26. The method of claim 25 further comprising backflushing said sample filter following step (D).