Apparatus for determining hemoglobin and white blood cell count in blood

• US 4,303,337 A
• Filed: 03/26/1979
• Issued: 12/01/1981
• Est. Priority Date: 03/26/1979
• Status: Expired due to Term

• Current Assignee: Coulter Electronics, Inc. (Danaher Corporation)
• Original Assignee: Coulter Electronics, Inc. (Danaher Corporation)
• Inventors: James, Bobby D., Starling, J. David, Simpson, Ronald O.
• Primary Examiner(s): Corbin, John K.
• Assistant Examiner(s): ARNOLD, BRUCE
• Application Number:
  US06/023,958
• Time in Patent Office: 981 Days
• Field of Search: 356/40, 356/41, 356/42, 356/72, 324/71 CP, 250/222 PC, 364/555
• US Class Current: 356/72
• CPC Class Codes: G01N 15/12 by observing changes in resistance or impedance across apertures when traversed by individual particles, e.g. by using the Coulter principle
• CPC Class Codes: G01N 21/85 Investigating moving fluids or granular solids

Abstract

A single instrument for photometrically determining hemoglobin content and electronically determining white blood cell count of a single sample suspension of blood. The instrument is provided with a calibration mode of operation independent of the run or normal operational mode of the instrument.

A vacuum system is described where vacuum is generated during the operating cycle only at periods when vacuum is required with an adjustable volume vacuum chamber interposed in the vacuum system to assure proper vacuum levels.

Carryover of one liquid to a next introduced second liquid in the test vessel is reduced by successive draining of said second liquid and reintroduction into said vessel of a replacement amount of said second liquid. The second liquid can be a sample of rinse liquid.

An hydraulic system is described as operating in conjunction with the pneumatic or vacuum system. The hydraulic system employs additional plural solenoid operated devices, each to perform a specific operational function during the operational cycle of the instrument.

Claims

1. In an electronic particle analysis apparatus wherein there is provided a hydraulic and pneumatic system for moving fluids by hydraulic means and by pneumatic means from selected locations to predetermined destinations in accordance with a selected operating cycle and wherein a vacuum level is to be established for employment only to perform selected functions during said operational cycle, the improvement comprising vacuum generating means for establishing said vacuum and control means coupled thereto for operating said vacuum generating means to draw vacuum only when vacuum is required to move fluid through scanning aperture means for particle study during said operational cycle.

2. The invention as claimed in claim 1 in which said vacuum generating means comprises a solenoid operated vacuum dispenser.

3. The invention as claimed in claim 1 in combination with first and second vessels, said first vessel having a particle suspension therein, scanning aperture means defining the sole communication between said first and second vessels, and means coupling said vacuum generating means to said vessels to move liquid therein from said first vessel through said scanning aperture means only during a selected part of said operational cycle, passage of said suspension for a given time period through said scanning aperture means being monitored to provide a count of said particles.

4. The invention as claimed in claims 1, 2 or 3 in which means are provided for controlling the degree of vacuum between selected upper and lower limits suitable for performing said liquid movement.

5. The invention as claimed in claims 1, 2 or 3 in which means are provided for controlling the degree of vacuum between upper and lower limits suitable for performing said liquid movement, said last means comprising selectively operable vent means for reducing the initially generated vacuum level to a defined limit.

6. The invention as claimed in claim 5 in which there is provided means for sensing the defined vacuum level limits and alarm means operated by said sensing means for indicating when the vacuum level is outside said limits.

7. The invention as claimed in claims 1, 2 or 3 in which an adjustable volume vacuum chamber is coupled within said pneumatic system to said vacuum generating means, and means for changing the volume of said vacuum chamber dependent upon the atmospheric pressure at site of use whereby to render the limits independent of changes in ambient atmospheric pressure at different sites of use.

8. The invention as claimed in claim 3 wherein said hydraulic means of the hydraulic and pneumatic system includes plural and solenoid controlled, hydraulically operated dispensers each coupled with a source of liquid, a coupling at said first vessel and a destination to perform a specific functional operation during the operational cycle including, respectively, rinsing of said first vessel with rinse liquid from a source thereof, draining said first vessel of liquid therein, and removing liquid which may have overflowed at the vicinity of said first vessel, and control means adapted to operate said respective dispensers at preselected intervals during the operational cycle.

9. The invention as claimed in claim 3 and means operable to drive liquid from said second vessel to said first vessel through said scanning aperture means at a selected time during said operational cycle for clearing said scanning aperture means.

10. The invention as claimed in claim 3 and first and second valve means coupled in said pneumatic means, said first valve means operable to introduce liquid to said pneumatic means and to said second vessel to direct said liquid toward said scanning aperture means and simultaneously to serve to reduce the generated vacuum level to the upper operational vacuum level limit and said second valve means operable to vent said pneumatic means to atmosphere at a selected time during said operational cycle.

11. The invention as claimed in claim 3 and means coupled to said first vessel for draining at least a portion of its contents therefrom and directing said drained portion to a waste receiver at a selected time during said operational cycle.

12. The invention as claimed in claim 11 in which said drained portion comprises the entire content of said vessel at the time of drain, and means to drain at least a portion of a second liquid commencing as the second liquid is introduced into said test vessel.

13. The invention as claimed in claim 12 in which said last mentioned portion is drained while the second liquid is being introduced into said test vessel.

14. The invention as claimed in claim 3 and in combination therewith, optical hemoglobinometer means for determining the hemoglobin content of a liquid sample suspension introduced into the said first vessel.

15. The invention as claimed in claims 3 or 14 and means for reducing carryover of a prior liquid to the next successively introduced liquid in said first vessel by draining at least a portion of last mentioned liquid from said test vessel.

16. The invention as claimed in claims 3 or 14 and means for reducing carryover of a prior liquid to the next successively introduced liquid in said first vessel by draining at least a portion of said last mentioned liquid from said test vessel immediately subsequent to its introduction to said test vessel.

17. The invention as claimed in claims 3 or 14 and means for reducing carryover of a prior liquid to the next successively introduced liquid in said first vessel by draining at least a portion of said last mentioned liquid from said test vessel simultaneously with its introduction.

18. The invention as claimed in claims 3 or 14 and means for reducing carryover of a prior liquid to the next successively introduced liquid in said first vessel by draining at least a portion of said last mentioned liquid from said test vessel, said portion comprising the full amount of second liquid introduced, the second liquid being re-introduced subsequent to said drain.

19. The invention as claimed in claims 3 or 14 and means for reducing carryover of a prior liquid to the next successively introduced liquid in said first vessel by draining at least a portion of said last mentioned liquid from said test vessel simultaneously with its introduction and electrical circuit means for detecting entry of said second liquid into said test vessel and causing said drain when such entry is detected.

20. The invention as claimed in claim 3 and an optical hemoglobinometer for determining hemoglobin content of a liquid introduced to said first vessel, said hemoglobinometer including means for monitoring transmittance of a beam of light through said first vessel and generating an electrical signal representative of the transmittance of at least a pair of liquids successively introduced into said first vessel, means for converting the signals representing each of said pair of liquids into respective pairs of d.c. voltages, one of said voltages having a lower voltage than the other of said pair and being applied to a first storing means, the second and higher of said voltages being applied to a second storing means, means for preserving the first voltage on said first storing means, means for comparing the first and second voltages, means for discharging said second voltage until a balance of said first and second voltages occurs, means for displaying the duration of said discharge, means to adjust the duration of said discharge on the second storing means for calibration of said device, and means to provide repetitive readout displays for reference thereto during the adjustment of the duration of said discharge.

21. The invention as claimed in claim 20 and oscillator means generating a continuous series of pulses, accumulating readout means to receive and visually display the accumulated number of said pulses, gate means interposed between said oscillator means and said accumulating readout means and operable upon initiation of said discharge to pass pulses to said readout means, said second voltage being discharged to a value equal to the first voltage and said gate means being blocked upon reaching of said last value.

22. In the combination of an electronic particle counting apparatus and an optical hemoglobinometer for providing respectively white blood cell count and hemoglobin content of a sample suspension as readable displays, the counting apparatus being of the type wherein particles of the sample suspension are caused to move through a scanning aperture whose effective impedance is changed with the passage of each particle therethrough, the change of impedance generating an electrical signal which can be counted, the improvement comprising said apparatus including a test vessel for receiving said sample suspension, a second vessel adjacent said test vessel, photometric means for monitoring said suspension when same is within said test vessel, scanning aperture means carried by at least one of said vessels and defining the sole communication therebetween, means, including electrode means, for establishing a current path within said scanning aperture means and between said vessels, means for monitoring and recording passage of particles through said scanning aperture means and circuit means coupled to readout means for receiving, accumulating and converting signals representing passage of said particles into a readable display, a pneumatic system operable to move sample suspension from said test vessel to said second vessel and a hydraulic system operable to move liquids from a source to and from said test vessel, said pneumatic system including a solenoid operated vacuum generating means coupled to said vessels and means to operate said vacuum generating means to generate a vacuum in accordance with a predetermined operating cycle only when vacuum is required to move the sample suspension through the scanning aperture.

23. The combination as claimed in claim 22 and said optical hemoglobinometer includes means for generating an electrical signal representative of the transmittance of said sample suspension in said vessel and that of a second liquid introduced successively therein, means for converting the signals representing each of said transmittances into respective pairs of d.c. voltages, the first one of said voltages having a lower voltage than the second and being applied to first storing means, the second of said two voltages having a higher value than the first and the higher of said voltage values being applied to a second storing means, means for comparing the first and second voltages, means for discharging the second voltage until the first and second voltages are equal and balance on said comparing means is reached, and readout means to display the duration of said discharge.

24. The combination as claimed in claim 23 and oscillator means generating a continuous series of pulses, gate means interposed between said oscillator means and said readout means and operable upon initiation of discharge to pass pulses to said readout means and to block passage of pulses to said readout means when balance is reached.

25. The combination as claimed in claim 23 and means establishing a calibration cycle, said sample suspension comprising a calibration solution having a known hemoglobin content, and means selectively operable during said calibration cycle for preserving the lower of said voltages on said first storing means, means for adjusting the duration of discharge of said second storing means to provide a readout representative of said known hemoglobin content and means for providing repetitive closely spaced readout displays for reference thereto during the adjustment of said last mentioned discharge duration.

26. The combination as claimed in claim 22 or 23 in which said hydraulic system of the hydraulic and pneumatic system includes means for introducing rinse liquid from a source thereof to said test vessel at selected time intervals, means for draining said test vessel also at selected time intervals and said last mentioned means being operable to effect at least a fractional drainage of said test vessel subsequent to the introduction of said liquid therein whereby to reduce carryover between successive introduction.

27. The combination as claimed in claim 22 in which said test vessel is drained, and a second liquid is introduced from a source thereof to said test vessel to replace said drained liquid, means for draining at least a fractional portion of said second introduced liquid from said test vessel upon introduction of said second liquid thereto.

28. The combination as claimed in claim 27 in which said second liquid portion is drained during introduction of said second liquid portion.

29. The combination as claimed in claim 27 in which said second liquid portion is drained immediately subsequent to its introduction.

30. The combination as claimed in claim 22 and valve means for coupling said pneumatic system into said hydraulic system selectively to bleed said pneumatic system to reduce the initially generated vacuum to selected operating vacuum level limits, said valve means operable also to direct the bleed from said pneumatic system to the vicinity of scanning aperture for flushing said vicinity at a selected time during said operational cycle.

31. The combination as claimed in claim 22 in which manually actuatable means are provided for flushing fluid through the scanning aperture means from the second vessel to the first vessel.

32. The combination as claimed in claim 22 or 23 and an adjustable volume vacuum chamber coupled to said vacuum generator.

33. The combination as claimed in claim 22 or 23 and said hydraulic system includes a solenoid controlled dispenser operable at a selected time during the operating cycle to drain overflowed liquids from the vicinity of said test vessel.

34. The combination as claimed in claim 22 or 23 and means to provide an audible periodic indication of the particle count whereby abnormalities therein may be detected.

35. The combination as claimed in claim 22 and electrical circuit means for detecting entry of the sample suspension into the test vessel, means for draining at least a portion of said sample suspension from said test vessel upon detection and prior to moving said sample suspension through the scanning aperture.

36. The combination as claimed in claim 35 which includes means for monitoring the transmittance of a beam of light through said test vessel, and said entry detecting circuit is enabled to cause said draining means to operate when said light beam is interrupted.

37. The combination as claimed in claim 23 and electrical circuit means for detecting entry of the suspension into the test vessel, means for draining at least a portion of said sample supension from said test vessel upon detection and prior to moving said sample suspension through the scanning aperture.

38. The combination as claimed in claim 37 which includes means for monitoring the transmittance of a beam of light through said test vessel, and said entry detecting circuit is enabled to cause said draining means to operate when said light beam is interrupted.