Particle density measuring system

• US 4,110,604 A
• Filed: 09/13/1977
• Issued: 08/29/1978
• Est. Priority Date: 11/04/1976
• Status: Expired due to Term

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Haynes, John L., Shoor, Bernard A.
• Primary Examiner(s): Thesz, Joseph M.
• Application Number:
  US05/832,893
• Time in Patent Office: 350 Days
• Field of Search: 235/92 PC, 235/92 PE, 235/92 CC, 235/92 PL, 324/71 CP, 364/555
• US Class Current: 377/10
• CPC Class Codes: G01N 15/132 Circuits
• CPC Class Codes: G01N 2015/012 Red blood cells
• CPC Class Codes: G01N 2015/018 Platelets
• CPC Class Codes: G01N 2015/1024 Counting particles by non-optical means

Abstract

A method and apparatus are provided for determining the count per unit volume, that is, the density of particles such as platelets in diluted whole blood. The invention involves use of known information, namely, the count per unit volume of other (reference) particles, such as red blood cells, also suspended in the same sample of liquid. The other particles are generally distinguishable from the particles of unknown count per unit volume by a difference in some measurable characteristic of the particles, such as size. One embodiment of the invention is characterized by generating electrical pulses which represent detected particles in a sample of liquid of undetermined volume; discriminating between pulses which have different characteristics; separately counting such pulses until the count of particles of known density reaches a corresponding preset number or until a predetermined period of time has elapsed, or until the entire sample of liquid under test has been tested; and displaying the total count of particles of previously unknown density. This total count either corresponds directly to the density of such particles or is an easily converted indication of such particle density.

Claims

1. In apparatus for measuring the concentration of particles of a first type in a fluid in which first and second types of particles are suspended, the first and second types of particles generally differing in a detectable physical characteristic, in which apparatus particles suspended in such fluid are sensed as said fluid is flowed through sensing means, and electrical pulses corresponding to said sensed particles are generated, the pulses having an electrical characteristic that corresponds to said physical characteristic,

the combination that comprises:

(a) means responsive to such electrical characteristics of said pulses for discriminating between types of particles in a specimen having different characteristics;

(b) means controlled by said discriminating means for generating separate signals corresponding to pulses generated by the particles in the specimen having the respective characteristics; and

(c) a register and means for setting said register in accordance with the concentration of said second type of particle in said specimen and means controlled by the setting of said register as well as said separate signals for producing an output signal representative of the concentration of particles of said first type in said specimen.

2. In apparatus for measuring the concentration of particles of a first type in a fluid in which first and second types of particles are suspended, the first and second types of particles generally differing in a detectable physical characteristic, in which apparatus particles suspended in said fluid are sensed as said fluid is flowed through sensing means, and electrical pulses corresponding to said sensed particle are generated, the pulses having an electrical characteristic that corresponds to said physical characteristic,

the combination that comprises:

(a) means responsive to such electrical characteristics of said pulses for discriminating between particles having different physical characteristics;

(b) means controlled by said discriminating means for generating two separate sets of signals corresponding to different proportions of said two types of particles;

(c) a register;

(d) means for setting said register in accordance with a standard concentration of said second type of particle when known; and

(e) means controlled by the set of said signals corresponding to the flow through said sensing means of a number of particles of said second type corresponding to said standard concentration and by said register for indicating the number of particles of said first type that has flowed concurrently through said sensing means.

3. In apparatus for measuring the concentration of particles of a first type in a fluid in which first and second types of particles are suspended, the first and second types of particles differing in a detectable physical characteristic, in which apparatus particles suspended in said fluid are sensed as a said fluid is flowed through sensing means and electrical pulses corresponding to said sensed particles are generated, the pulses having electrical characteristics that depend on the physical characteristics of said particles, and the pulses corresponding to particles of said first and second types having amplitudes that extend over corresponding different but overlapping first and second ranges respectively,

the combination that comprises:

(a) first means for detecting pulses having an electrical characteristic in a first range corresponding primarily to particles of said first type;

(b) second means for detecting pulses having an electrical characteristic in a second range corresponding primarily to particles of said second type;

(c) means controlled by said first and second means for generating a first and a second stream of pulses respectively; and

(d) means controlled by said two streams of pulses to produce a signal representative of the ratio of concentrations of said two types of particles in said fluid including a register and means for setting said register in accordance with the concentration of said second type of particle, and means controlled by the setting of said register as well as said two streams of particles for indicating the concentration of said first type of particle in said fluid.

4. In apparatus for measuring the concentration of particles of a first type in a fluid in which first and second types of particles are suspended, the first and second types of particles generally differing in a detectable physical characteristic, in which particles suspended in said fluid are sensed as said fluid is flowed through sensing means, and electrical pulses corresponding to said sensed particles are generated, the pulses having an electrical characteristic that corresponds to said physical characteristic,

the combination that comprises:

(a) means responsive to such electrical characteristics of said pulses for discriminating between particles differing in said physical characteristic;

(b) means controlled by said discriminating means for generating a first stream of pulses and a second stream of pulses corresponding to particles differing in said physical characteristics;

(c) means for registering a condition corresponding to the concentration of said second type of particle in said fluid;

(d) means controlled by said two streams of pulses and said registered condition for producing an output signal representative of the concentration of said first type of particle in said fluid; and

(e) display means for displaying said signal.

5. In apparatus for determining the particle density of a first type of particle suspended in a fluid in which a second type of particle is also suspended, wherein the first and second types of particles differ in a physical characteristic and wherein the particle density of the second type of particle is known, the improvement comprising:

a transducer adapted for detecting particles of the first and second types suspended in such a fluid and also adapted for generating an electrical signal corresponding to each detected particle, said signal being generally representative of whether said detected particle is a particle of the first type or of the second type;

a discriminator adapted for receiving said electrical signals and for separately generating a first electrical pulse for each received electrical signal generally representative of a particle of the first type and a second electrical pulse for each received electrical signal generally representative of a particle of the second type;

a first counter adapted for counting said first electrical pulses and for producing electrical count signals corresponding to said first count;

a second counter adapted for counting said second electrical pulses and for producing electrical count signals corresponding to said second count; and

means responsive to said count signals to stop counting by said first counter when said second count reaches a predetermined number corresponding to the known density of said second type of particle.

6. Apparatus for determining particle density as defined in claim 5, further comprising means for registering said first count in a visual display unit and means for displaying the value of said first count when said second count reaches said predetermined number.

7. An apparatus for determining the platelet density of a blood sample of undetermined volume the sample having a red blood cell density, the apparatus adapted for connection to a transducer adapted for detecting particles such as platelets and red blood cells in a blood sample, the transducer also adapted for generating an electrical signal corresponding to each detected particle, said signal being representative of where said detected particle is generally a platelet or is generally a red blood cell, the apparatus comprising:

discriminating means adapted for receiving said electrical signals and for separately generating a first electrical pulse for each received electrical signal generally representative of a platelet and a second electrical pulse for each received electrical signal generally representative of a red blood cell;

first means for counting said first electrical pulses;

second means for counting said second electrical pulses; and

means for stopping said first counting means when said second counting means attains a predetermined count for determining said platelet density.

8. In apparatus for determining the platelet density of a blood sample of undetermined volume, the sample having a red blood cell density, which apparatus is adapted for connection to a transducer adapted for detecting platelets and red blood cells in a blood sample, said transducer also being adapted to generate an electrical signal in one range of amplitudes generally corresponding to each detected platelet and an electrical signal in another range of amplitudes generally corresponding to each detected red blood cell:

a discriminator adapted for receiving said electrical signals and for separately generating a first electrical pulse for each received electrical signal the amplitude of which is representative of a detected platelet and a second electrical pulse for each received electrical signal the amplitude of which is representative of a detected red blood cell;

a first counter for counting said first electrical pulses;

a second counter for counting said second electrical pulses; and

means responsive to said second counter and controlling said first counter for stopping said first counter when the count produced by said second counter corresponds to said red blood cell density.

9. An apparatus for determining particle density as defined in claim 8, the discriminator comprising:

a lower threshold detector for generating a first detection signal for each transducer-generated electrical signal having an amplitude that exceeds a lower threshold;

an upper threshold detector for generating a second detection signal for each transducer-generated electrical signal having an amplitude that exceeds an upper threshold; and

gate-circuit means adapted for receiving said first and second detection signals and also adapted for generating only said first electrical pulse when only said first detection signal is received, and for generating only said second electrical pulse when said first and second detection signals are received substantially simultaneously.

10. An apparatus for determining particle density as defined in claim 9, the discriminator further comprising:

a peak detector for generating a third detection signal when each transducer-generated electrical signal reaches its peak amplitude;

said gate-circuit means being also adapted for receiving said third detection signal and for generating said first or second electrical pulse only when receiving said third detection signal.

11. An apparatus for determining particle density as defined in claim 8, the discriminator further comprising means for detecting a peak level of each transducer-generated electrical signal and means for generating a peak-holding electrical signal corresponding to said each transducer-generated electrical signal, each said peak-holding electrical signal reaching and maintaining said peak level of said corresponding transducer-generated electrical signal.

12. An apparatus for determining particle density as defined in claim 11, said discriminator peak level detecting means comprising means responsive to only the first occurring peak of said transducer-generated electrical signal.

13. An apparatus for determining particle density as defined in claim 11, said discriminator further comprising means for resetting said peak-holding electrical signal generating means.

14. An apparatus for determining particle density as defined in claim 8, at least one of said counters comprising a prescaler device for dividing by a known factor, the number of electrical pulses counted.

15. An apparatus for determining particle density as defined in claim 14, said prescaler device comprising:

settable integer means and logic circuit means responsive to the setting of said integer means whereby said known factor corresponds to said setting.

16. A method of ascertaining the particle density of a first type of particle suspended in a fluid in which a second type of particle is also suspended wherein the first and second types of particles generally differ in a physical characteristic, comprising the following steps:

(a) measuring the particle density of said second type of particle;

(b) flowing a sample of said fluid through a sensing zone;

(c) sensing particles suspended in said fluid sample as said particles pass through said sensing zone;

(d) generating electrical pulses corresponding to sensed particles, such pulses having different electrical characteristics that depend primarily upon differences in physical characteristics of the two types of particles;

(e) electrically discriminating between pulses according to their electrical characteristics by separately detecting first and second pulses;

(f) electrically separately counting first pulses and second pulses having different electrical characteristics to produce first and second counts; and

(g) detecting said first count when said second count attains a value corresponding to the density of said second type of particle in said fluid.

17. In a method of ascertaining the particle density of a first type of particle suspended in a fluid in which a second type of particle is also suspended, wherein the first and second types of particles generally differ in a physical characteristic and wherein the particle density of the second type of particle is known;

the steps;

(a) flowing a sample of said fluid through a sensing zone;

(b) sensing particles suspended in said fluid sample as said particles pass through said sensing zone;

(c) generating electrical pulses corresponding to the particles sensed, each pulse having a different electrical characteristic that corresponds respectively to said different physical characteristics;

(d) utilizing said electrical characteristic of said each pulse to discriminate first pulses primarily generated by said sensing of said first type of particle from second pulses primarily generated by said sensing of said second type of particle;

(e) separately counting said first pulses and said second pulses to produce first and second counts respectively until said second count reaches a predetermined number that corresponds to said known particle density; and

(f) developing an electrical signal representative of said first count when said second count equals said predetermined number.

18. In a method of ascertaining particle density as defined in claim 17, the step of stopping the counting of said first pulses when said second count equals said predetermined number.

19. A method of ascertaining particle density as defined in claim 17, further comprising the step of automatically displaying said first count referred to in step f).

20. A method of ascertaining the density of platelets suspended in a sample of blood of undetermined volume in which red blood cells are also suspended, wherein the density of the red blood cells is known;

the method comprising the following steps;

(a) flowing such a sample of blood through a sensing zone;

(b) sensing platelets and red blood cells suspended in said blood sample as said sample flows through said sensing zone;

(c) generating an electrical pulse corresponding to each platelet and each red blood cell sensed, each pulse having an amplitude that corresponds, respectively, to the sizes of said platelets and said red blood cells, said amplitudes being separable by a threshold into a lower-amplitude group corresponding generally to platelets and into a higher-amplitude group corresponding generally to red blood cells;

(d) detecting whether the amplitude of said each pulse is above or below said threshold to discriminate first pulses generated primarily by said sensing of said platelets from second pulses generated primarily by said sensing of said red blood cells;

(e) separately counting said first pulses and said second pulses to produce first and second counts, respectively, until said second count reaches a predetermined number that corresponds to said known red blood cell density; and

(f) automatically detecting and displaying said first count when said second count substantially equals said predetermined number whereby said noted first count corresponds to the density of said platelets.

21. In a method of ascertaining the particle density of a first type of particle suspended in a fluid in which a second type of particle is also suspended, wherein the first and second types of particles differ in a physical characteristic, the steps of:

(a) measuring the particle density of said second type of particle;

(b) flowing a sample of said fluid through a sensing zone;

(c) sensing particles suspended in said fluid sample as said particles flow through said sensing zone;

(d) generating an electrical pulse corresponding to each particle sensed, each pulse having a different electrical characteristic that corresponds, respectively, to said different physical characteristics;

(e) utilizing said electrical characteristics of said pulses to discriminate first pulses generally generated by said sensing of said first type of particle from second pulses generally generated by said sensing of said second type of particle;

(f) separately counting said first pulses and said second pulses to produce first and second counts, respectively, until said second count reaches a predetermined number that corresponds to said particle density of said second type of particle; and

(g) automatically displaying said first count when said second count equals said predetermined number.

22. In a method of ascertaining particle density as defined in claim 21, comprising the step of stopping the counting of said first pulses when said second count equals said predetermined number.

23. A method of ascertaining particle density as defined in claim 21, comprising the step of stopping said counting of said first pulses and said counting of said second pulses when said second count equals said predetermined number.

24. In a method of ascertaining the particle density of platelets suspended in a sample of blood of undetermined volume in which red blood cells are also suspended, the steps:

(a) measuring the red blood cell density of such a sample;

(b) flowing said sample through a sensing zone;

(c) sensing each platelet and each red blood cell suspended in said sample as each platelet and red blood cell is flowed through said sensing zone;

(d) generating an electrical pulse corresponding to each platelet and red blood cell sensed, each said pulse having an amplitude that corresponds to the size of the particle sensed;

(e) utilizing said pulse amplitudes to discriminate first pulses generally generated by said sensing of said platelets from second pulses generally generated by said sensing of said red blood cells;

(f) separately counting said first pulses and said second pulses to produce first and second counts, respectively, until said second count reaches a predetermined number that corresponds to said density of said red blood cells; and

(g) automatically displaying said first count when said second count equals said predetermined number whereby the density of said platelets is ascertained.

25. In apparatus for measuring the concentration of particles of a first type in a fluid in which first and second types of particles are suspended, the first and second types of particles generally differeing in a detectable physical characteristic, in which apparatus particles suspended in such fluid are sensed as said fluid is flowed through sensing means, and electrical pulses corresponding to said sensed particles are generated, the pulses having an electrical characteristic that corresponds to said physical characteristic,

the combination that comprises:

(a) means responsive to such electrical characteristics of said pulses for discriminating between types of particles in a specimen having different characteristics;

(b) means controlled by said discriminating means for generating separate signals corresponding to pulses generated by the particles in the specimen having the respective characteristics; and

(c) a register and means for setting said register in accordance with the concentration of said second type of particle in said specimen and means controlled by the setting of said register as well as said separate signals for producing an output signal representative of the concentration of particles of said first type in said specimen,

said concentration of said second type of particle being in percent volume and including means for converting one of said separate signals to a digital format corresponding to such concentration such converter means comprising;

charge storage means;

analog input signal means responsive to said signal corresponding to said second type of particle for charging said charge storage means toward a level proportional to the magnitude of said signal;

reference comparator means for comparing said level of charge in said storage means to a reference;

charge dispensing means responsive to said comparator means to reduce said level of charge toward said reference; and

common timing means for enabling said analog input signal means and said charge dispensing means during a common time interval of fixed duration and for producing a digital format signal corresponding to said concentration.