US3864551A

US3864551A - Coincidence correction circuit

Info

Publication number: US3864551A
Application number: US447530A
Authority: US
Inventors: Arthur Oefinger
Original assignee: GENERAL SCIENCE CORP
Current assignee: Biochem Immunosystems US Inc; GENERAL SCIENCE CORP
Priority date: 1974-03-01
Filing date: 1974-03-01
Publication date: 1975-02-04
Anticipated expiration: 1992-02-04
Also published as: JPS50120880A; NL7502387A; ES435131A1; FR2262835A1; NL168333B; ZA75616B; DE2505837B2; NL168333C; JPS5639417B2; FR2262835B1; GB1468332A; DE2505837A1; AU7808275A; BE826007A; DE2505837C3; CA1013434A

Abstract

For use with a particle counting system, circuitry for correction for the coincident passage of multiple particles through a metering aperture. A read-only memory is employed to store data representing predetermined counting levels at which corrections are to be made during a counting sequence and at such counting levels a correction pulse is added to the then measured particle count to provide an output count which is continuously corrected in accordance with the actual nature of the accumulating coincidence error.

Description

O United States Patent [111 3,864,551

Oefinger [4 Feb. 4, 1975 COINCIDENCE CORRECTION CIRCUIT [75] Inventor: Arthur Oefinger, Stratford, Conn. i gzg iys rgzgzg m Jr [73] Assignee: General Science Corp., Bridgeport, Attorney, Agent, or Fhm-Weingarteni Maxham &

COIIH- Schurgin [22] Filed: Mar. 1, 1974 [21] Appl. NO.Z 447,530 [57] ABSTRA CT For use with a particle counting system, clrcultry for correction for the coincident passage of multiple parti- [52] 235/92 235/92 235/92 cles through a metering aperture. A read-only memory 324/71 CP is employed to store data representing predetermined [51] hit. Cl. G06!!! 11/00, H03k 21/34 counting levels at which corrections are to be made [58] Field of Search 235/92 PC, 92 PL; during a counting Sequence and at Such counting 324/71 CP els a correction pulse is added to the then measured particle count to provide an output count which is [56] References C'ted continuously corrected in accordance with the actual UNITED STATES PATENTS nature of the accumulating coincidence error.

3,209,130 9/1965 Schmidt 235/92 PL 3,686,665 8/1972 Elias et al. 235/92 PL 11 3 Draw ADDRESS REGISTER MULTI- PLEXER CONTROL CORRECTED COUNT PATENTED FEB 4|975 7 /2O CONDUCTIVITY Y J r 1 I PUMP I w v 11 W VOLUME' WASTE I I METERING ,VESSEL' v /"14 -12 70 28 L i 2 CONTROLS 'Y' f LOGIC COUNT 24g CIRCUITRY DISPLAY g 1.

/-34, MV INPUT I 32 COUNT MV CLK 44 46V 40 ,2, 38 V NAND G ADDRESS ROM MULTI- CORRECTED REGISTER ,PLExER 42 OR COUNT NAND Flg. 2. E

.coNTRoL @3 TO NAND GATE TO NAND GATE I COINCIDENCE CORRECTION CIRCUIT FIELD OF THE INVENTION incidence error caused by coincident passage of multiple particles through a metering aperture,

BACKGROUND OF THE INVENTION Systems are known for counting blood cells or other particles suspended in a liquid, a preferred system being shown in US. Pat. No. 27,902 assigned to the assignee of the present invention. In such a system electrical pulses are provided in response to the passage of particles through a metering aperture of a transducer or conductivity cell which is disposed within a fluid path and has electrodes on respective opposite sides of the aperture. The impedance of the fluid path is materially altered by the presence of a particle within the aperture, resulting in production of electrical pulses corresponding to the number of particles passing through the aperture and which pulses are electronically counted to provide an output indication of particle count. A known volume of particle-containing liquid is usually metered by appropriate means to provide a particle count for a known volume of liquid.

During operation an error known as coincidence error arises by reason of the coincident or nearly coincident passage of more than one particle through the metering aperture and which is sensed as a signle particle, with the result that the number of measured particles is lower than the actual particle count for a given quantity of sample liquid. The error is statistically predictable for known particle concentrations and metering aperture sizes, and correction charts are usually employed to derive a corrected particle count. The use of a correction chart is, of course, time consuming and itself productive of error due to misreading of the chart or erroneous copying of correction numbers. Automated means have been proposed for providing a corrected particle count, one such means being shown in US. Pat. No. 3,626,164 in which different corrections are applied to the measured count after specific numbers of counts as determined by a plurality of decade counters to provide an output count which is corrected somewhat for coincidence error. Continuous correction throughout the counting range is not provided nor is the correction in precise conformity to the real error which arises.

SUMMARY OF THE INVENTION In accordance with the present invention a coincidence correction circuit provide correction which is substantially in conformity with the actual error which arises in a particle counting system and which provides effectively continuous correction for such error to produce a corrected count throughout the entire counting range. At predetermined counting levels, representations of which are stored in a read-only memory, a correction pulse is added to the accumulating measured particle count to correct the count in accordance with the statistically determined actual nature of the accumulating error.

DESCRIPTION OF THE DRAWINGS The invention will be more fully understood from the 2 following detailed description taken in conjunction with the accompanying drawings, in which:

FIG. 1 is a schematic representation of a particle counting system in which the invention is useful; 3

FIG. 2 is a block diagram representation of a coincidence correction circuit according to the invention; and

FIG. 3 is a block diagram representation of a typical implementation of the circuitry of FIG. 2.

DETAILED DESCRIPTION OF THE INVENTION A particle counting system in which the invention is useful is shown diagrammatically in FIG. 1 and which itself is the subject of US. Pat. No. 27,902. This system includes a conductivity cell or transducer I0 having a metering aperture and electrodes therein for providing electrical pulses on output line 12 corresponding and in response to particles passing through the aperture thereof. Particle-containing liquid is drawn from a sample container into cell 10 via an input tube 14 and exits through a-tube 16 which terminates in a waste vessel 18 to which is also coupled to pump 20. Pump 20 provides a negative pressure for drawing sample liquid through cell 10 for analysis during a counting run. The output pulses from cell 10 are applied to an amplifier 22, the output of which is coupled to logic circuitry 24 which processes the received pulses to provide an output signal to a count display 26 which visually indicates the particle count for a given quantity of sample liquid. The sample quantity being analyzed is determined by volume metering means 28 which senses a known quantity of sample liquid flowing through tube 16 and provides electrical start and stop signals to logic circuitry 24 to define a counting interval within which a particle count is accumulated for display. Appropriate controls 30 are coupled to logic circuitry 24 for operation thereof.

The passage of a particle through the metering aperture of conductivity cell 10 alters the impedance of the fluid path within the cell, causing the provision of a cor responding'electrical pulse which is then processed for accumulating a particle count. In practice, two or more particles can simultaneously pass through the metering aperture, giving rise to the production of a single pulse which erroneously denotes the passage of a single particle. The error occasioned by such multiple particle passages is termed coincidence error and produces a lower than true count. The coincidence error is statistically predictable for known aperture sizes and concentrations of sample liquid and the correction is required at predetermined counts of a sequence of measured counts. The present invention provides the circuitry for augmenting the measured count throughout a counting run by addition of correction pulses necessary to provide a corrected output count actually representative of the true count.

The novel circuitry is shown in FIG. 2 and includes first and

second multivibrators

32 and 34, each of which receive the electrical pulses representative of measured particle count. Multivibrator 32 provides output pulses as a clock signal to an address register 36 and also provides its output pulses as one input of OR gate 38, the output of which gate is the corrected count. The output pulses from multivibrator 34 are applied as one input to

NAND gates

40 and 42, the outputs of which are applied to respective inputs of OR gate 38. Address register 36 has its output lines coupled to the inputs of a read-only memory 44, the output of which is coupled to a multiplexer 46 which provides first and second output signals to

gates

40 and 42 respectively. A control signal is applied from a suitable source to an input of gate 40 and via an inverter 48 to an input of gate .42. The

multivibrators

32 and 34 typically are one shot multivibrators, multivibrator 32 being triggered on the trailing edge of an input pulse while multivibrator 34 is triggered on leading edge of the input pulse. As a result, a predetermined time delay is provided between the respective output pulses from the multivibrators sufficient to permit signal processing for providing correction data.

The address register 36 provides an output code corresponding to the number of clock pulses applied thereto and which code addresses a read-only memory 44 which has stored therein data representative of the coincidence points of a correction chart at which additional pulses are to be added to a measured count. At the addresses of the stored data, memory 44 provides an output code to multiplexer 46 which produces an output signal to

gate

40 or 42 to cause an additional pulse to be added to the measured count for correction. When the invention is employed in a system for counting different types of particles such as red blood cells, white blood cells or platelets, the coincidence error is different due to the different dilutions and size of apertures required. The read-only memory 44 can have stored therein correction data for different needed corrections. For example, memory 44 can store correction data for multiple sets of data. Only one

NAND gate

40 or 42 is operative in accordance with the value of the control signal applied thereto depending upon the type of particles, say red cells or white cells, being counted.

In operation, pulses provided by a particle counting system transducer and of a number representative of measured particle count are applied to multivibrator 32 which provides corresponding output pulses to OR gate 38 which, in turn, provides output pulses for subsequent processing and display. The input pulses are also applied to multivibrator 34 which provides corresponding pulses to an input of NAND gates 40- and 42. A control signal is applied to one or the other of

gates

40 and 42 to enable a selected one of these gates in accordance with the type of blood cells being counted. For example, during a red blood cell counting run an enabling signal can be applied to gate 40 while gate 42 is enabled during a white blood cell counting run. In the illustrated embodiment the control signal is a logic level applied to gate 40 and the inverse of which is applied to gate 42. Thus, a control input of logic level one will provide a one level'to gate 40 and a zero level to gate 42. Alternatively, a control level of zero will pro-' vide a zero level at gate 40 and a one level at gate 42.

Address register 36 is operative in response to the clock pulses provided by multivibrator 32, and which in turn is representative of the input pulses to provide a parallel output code to sequentially address memory 44 in accordance with successive values of the received particle count. At selected addresses of the data stored in memory 44, the memory provides an output code to multiplexer 46 which in turn provides an output signal to

gates

40 and 42. The enabled one of

gates

40 or 42, upon receipt of a signal from multiplexer 46 and multivibrator 34, provides an output pulse to OR gate 38 which provides a correction pulse for addition to the then count.

Read-only memory 44 is typically a semiconductor memory programmed in accordance with the corrections needed for a particular aperture size and sample liquid dilution and which in the illustrated embodiment -has stored data for both red cell and white cell coincidence correction. The multiplexer 46 will decode the memory output codes provided for both red cell and white cell coincidence correction, but, as described above, only the intended correction information is employed as determined by the enablement of

gate

40 or 42 depending upon whether red or white cells are being counted.

The novel circuitry is typically implemented in integrated circuit form and with the read-only memory programmed in accordance with the configuration of a particular metering aperture employed in the transducer ofa particle counting system and the dilution ratios of the sample liquid.

A preferred implementation of the novel circuit is shown in FIG. 3 wherein the address register 36 is comprised of three integrated circuit binary counters 50, 52 and 54, such as Texas Instrument type 7493 counters. The clock signal from multivibrator 32 is applied to the clock input of counter 50 and the D output is coupled to the clock input of counter 52 while the D output thereof is, in turn, coupled to the input of counter 54. The A and B outputs of counter 50 are coupled to the respective control inputs of multiplexing

gates

56 and 58 which gates comprise the multiplexer 46 of FIG. 2.

Gates

56 and 58 are typically Texas Instruments type 74153 multiplexers. The C and D outputs of counter 50 are applied as inputs to read-only memory 44 while the four outputs of counter 52 and the A and B outputs of counter 54 are also applied as inputs to memory 44.

From the foregoing, it will be appreciated that the invention provides correction for coincidence error in accordance with the actual error accumulating throughout a particle counting run and on an effectively continuous basis. The invention in actual implementation may take a variety of forms to suit specific constructional and operational requirements without departing from the spirit and true scope of the invention. Accordingly, it is not intended to limit the invention by what has been particularly shown and described, except as indicated in the appended claims.

What is claimed is:

1. In a particle counting system including a transducer having an aperture through which particlecontaining liquid is caused to flow and means for generating electrical pulses in response to particles passing through said aperture, circuitry for providing correction for the coincident passage of multiple particles through said aperture, said circuitry comprising:

means for providing first pulses in response to said electrical pulses and representative of measured particle count;

means for providing second pulses in response to said electrical pulses;

memory means containing data representing predetermined particle counts at which correction is to occur; address means operative in response to said first pulses to address said memory means to cause the provision of parallel output codes therefrom;

multiplexer means operative in response to said parallel output codes to provide at least one gating signal;

first gate means operative in response to said at least one gating signal and to said second pulses to provide a correction pulse; and

second gate means operative in response to said first pulses and said correction pulse to provide output pulses representative of a corrected particle count.

2. The invention according to claim 1 wherein said first pulse and second pulse providing means each include a multivibrator operative to provide an output pulse in response to a corresponding input pulse thereto.

3. The invention according to claim 2 wherein said multivibrator providing said first pulses is triggered on the trailing edge of said electrical pulses and said multivibrator providing said second pulses is triggered on the leading edge of said electrical pulses, thereby to provide a predetermined time delay between respective first and second pulses sufficient for coincidence correction processing.

4. The invention according to claim 1 wherein said memory means includes a read-only memory programmed with said data representing predetermined particle counts at which correction is to occur for a particularly configured metering aperture and dilution ratio of the partical-containing liquid.

5. The invention according to claim 4 wherein said address means includes an address register providing successive address codes in response to successive first pulses for addressing said read-only memory in accordance with the number of first pulses received.

6. The invention according to claim 4 wherein said first gate means includes a NAND gate coupled to said multiplexer means and to said second pulse providing means;

and wherein said second gate means includes an OR gate coupled to said NAND gate and to said first pulse providing means.

7. The invention according to claim 1 wherein said memory means is a read-only memory containing data representative of said predetermined particle counts for different types of particles;

and wherein said first gate means includes first and second NAND gates operative to receive said second pulses and gating signals from said multiplexer means; and

enabling means coupled to said NAND gates and operative to enable a selected one thereof in accordance with the type of particles being counted.

8. The invention according to claim I wherein said memory means is a read-only memory containing data representative of said predetermined particle counts for different types of particles;

said multiplexer means is operative-in response to said output codes from said read-only memory to provide at least one gating signal for each of said different types of particles; and said first gate means includes first and second gates operative to receive respective ones of said gating signals and said second pulses; and

enabling means coupled to said first and second gates and operative to enable a selected one thereof in accordance with the type of particles being counted.

9. The invention according to claim 8 wherein said second gate means includes an OR gate coupled to said first and second gates and to said first pulse providing means.

10. The invention according to claim 9 wherein said enabling means includes:

a source of control signals;

means coupling said source to said first gate; and

inverter means coupling said source to said second gate.

ll. The invention according to claim 1 wherein said memory means includes a read-only memory programmed with said data representing predetermined particle counts at which correction is to occur, said data being statistically determined in accordance with the dilution ratio of the particle-containing liquid and the transducer aperture size.

Claims

1. In a particle counting system including a transducer having an aperture through which particle-containing liquid is caused to flow and means for generating electrical pulses in response to particles passing through said aperture, circuitry for providing correction for the coincident passage of multiple particles through said aperture, said circuitry comprising: means for providing first pulses in response to said electrical pulses and representative of measured particle count; means for providing second pulses in response to said electrical pulses; memory means containing data representing predetermined particle counts at which correction is to occur; address means operative in response to said first pulses to address said memory means to cause the provision of parallel output codes therefrom; multiplexer means operative in response to said parallel output codes to provide at least one gating signal; first gate means operative in response to said at least one gating signal and to said second pulses to provide a correction pulse; and second gate means operative in response to said first pulses and said correction pulse to provide output pulses representative of a corrected particle count.

6. The invention according to clAim 4 wherein said first gate means includes a NAND gate coupled to said multiplexer means and to said second pulse providing means; and wherein said second gate means includes an OR gate coupled to said NAND gate and to said first pulse providing means.

7. The invention according to claim 1 wherein said memory means is a read-only memory containing data representative of said predetermined particle counts for different types of particles; and wherein said first gate means includes first and second NAND gates operative to receive said second pulses and gating signals from said multiplexer means; and enabling means coupled to said NAND gates and operative to enable a selected one thereof in accordance with the type of particles being counted.

8. The invention according to claim 1 wherein said memory means is a read-only memory containing data representative of said predetermined particle counts for different types of particles; said multiplexer means is operative in response to said output codes from said read-only memory to provide at least one gating signal for each of said different types of particles; and said first gate means includes first and second gates operative to receive respective ones of said gating signals and said second pulses; and enabling means coupled to said first and second gates and operative to enable a selected one thereof in accordance with the type of particles being counted.

10. The invention according to claim 9 wherein said enabling means includes: a source of control signals; means coupling said source to said first gate; and inverter means coupling said source to said second gate.

11. The invention according to claim 1 wherein said memory means includes a read-only memory programmed with said data representing predetermined particle counts at which correction is to occur, said data being statistically determined in accordance with the dilution ratio of the particle-containing liquid and the transducer aperture size.