Flow cytometer

Claim 2

A flow cytometer for detecting and identifying particles in a fluid, said flow cytometer having means for moving said particles to a detection station, means for directing energy at said detection station so that said particles intersect said energy when at said detection station, and a plurality of detectors for providing analog electric signals manifesting different results of each particle intersecting said energy, said flow cytometer comprising: a plurality of analog signal processors, each responsive to only one detector signal for processing, delaying and storing analog data manifesting the signal provided thereto; first controller means responsive to a trigger signal from a selected one of said analog signal processors for determining that a particle is intersecting said energy, said trigger signal being time related to the signals from said detectors, said first controller means providing signals to each of said analog signal processors for causing the storage of a delayed version of the signal applied thereto; second controller means for polling each of said plurality of analog signal processors to receive and digitize said delayed signal stored thereby and to further process said received and digitized signals in order to identify said detected particle and each analog signal processor stores a signal related to the signal provided thereto, and provides a data signal to said second controller means in response to a poll signal therefrom, each analog processor including amplifying means for amplifying each stored signal to provide said data signal, said amplifying means amplifying said stored signal with one of a first gain or a second gain, said second gain being greater than said first gain, said amplifying means amplifying said stored signal with said second gain unless the signal value amplified with said second gain exceeds a certain value.

Claim 3

The flow cytometer according to claim 1 wherein each of said analog signal processors has first and second analog signal storage means, said first storage means storing data related to said delayed signal and said second storage means storing data related to the data stored by said first storage means during the time said second controller means polls each analog signal processor.

Claim 4

The flow cytometer according to claim 2 wherein said first storage means is enabled to store data from a newly detected particle after the data previously stored thereby has been stored in said second storage means.

Claim 5

The flow cytometer according to claim 1 wherein each analog signal processor provides an associated control signal to said second controller means manifesting the one gain of said amplifying means for the data signal being provided.

Claim 6

The flow cytometer according to claim 4 wherein said second controller means includes an analog to digital converter for converting the analog signal provided thereto to a digital signal, said second controller means digital signal being limited to N bits, at least one of which is said control signal and the remaining ones of which contain the digital signal from said analog to digital converter.

Claim 7

The flow cytometer according to claim 5 wherein each of said analog signal processors has first and second analog signal storage means, said first storage means storing data related to said delayed signal and said second storage means storing data related to the data stored by said first storage means during the time said second controller means polls each analog signal processor.

Claim 8

The flow cytometer according to claim 6 wherein said signal provided for storage to said second storage means is amplified by said amplified means.

Claim 9

The flow cytometer according to claim 1 wherein each of said analog signal processors has first and second analog signal storage means, said first storage means storing data related to said delayed signal and said second storage means storing data related to the data stored by said first storage means during the time said second controller means polls each analog signal processor.

Claim 10

The flow cytometer according to claim 8 wherein said signal provided for storage to said second storage means is amplified by said amplified means.

Claim 11

A flow cytometer for detecting particles in a fluid and determining information regarding said particles, said flow cytometer having means for moving said particles to a detection station, means for directing energy at said detection station so that said particles intersect said energy when at said detection station, and detector means for providing an electric signal manifesting the result of each particle intersecting said energy, said flow cytometer further having a detection circuit comprising: means for detecting the presence of a particle in said detection station and providing an electric signal manifesting a parameter of said detected particle; first storage means for storing an electric signal related to said detector means signal after said means for detecting has detected a particle in said detection station; second storage means for storing, on command, an electric signal related to the signal stored by said first storage means; processor means responsive to the electric signal stored by said second storage means for processing the electric signal stored by said second storage means to obtain the information regarding each particle; command means for enabling said second storage means to store said electric signal related to the signal stored by said first storage means after said processor means has completed processing the electric signal previously stored by said second storage means and said means for detecting has detected the presence of another particle in said detection station, said command means further resets said first storage means after enabling said second storage means to store said electric signal related to the signal stored by said first storage means and said command means detects the time of occurrence of a particle entering said detection station in response to said detector means signal applied thereto; and said flow cytometer further includes delay means for delaying said detector means signal by a delay time prior to said first storage means.

Claim 12

A flow cytometer for detecting particles in a fluid and determining information regarding said particles, said flow cytometer having means for moving said particles to a detection station, means for directing energy at said detection station so that said particles intersect said energy when at said detection station, and detector means for providing an electric signal manifesting the result of each particle intersecting said energy, said flow cytometer further having a detection circuit comprising: means for detecting the presence of a particle in said detection station and providing an electric signal manifesting a parameter of said detected particle; first storage means for storing an electric signal related to said detector means signal after said means for detecting has detected a particle in said detection station; second storage means for storing, on command, an electric signal related to the signal stored by said first storage means; processor means responsive to the electric signal stored by said second storage means for processing the electric signal stored by said second storage means to obtain the information regarding each particle; command means for enabling said second storage means to store said electric signal related to the signal stored by said first storage means after said processor means has completed processing the electric signal previously stored by said second storage means and said means for detecting has detected the presence of another particle in said detection station, said command means further resets said first storage means after enabling said second storage means to store said electric signal related to the signal stored by said first storage means and said command means detects the time of occurrence of a particle entering said detection station in response to said detector means signal applied thereto; and said flow cytometer further includes delay means for delaying said detector means signal by a delay time prior to said first storage means.

Claim 13

The flow cytometer according to claim 10 wherein said delay means signal is processed and provided to said first storage means at a first time, less than said delay time, after detecting the time of occurrence of a particle entering said detection station.

Claim 14

The flow cytometer according to claim 11 wherein said command means detects the time of occurrence of a particle leaving said detection station in response to said detector means signal applied thereto, and enables said first storage means to store said processed delay means signal at a second time, greater than said delay time, following the detection of said particle leaving said detection station.

Claim 15

The flow cytometer according to claim 12 wherein said delay means signal is processed such that the time domain integral is stored in said first storage means.

Claim 16

The flow cytometer according to claim 12 wherein said delay means signal is processed such that the peak value thereof is stored in said first storage means.

Claim 17

The flow cytometer according to claim 10 wherein said command means includes threshold means to which said detector means signal is provided, said threshold means providing a first signal after said detector means signal exceeds a threshold value and a second signal after said detector means signal falls below said threshold value, said first signal being provided to permit further processing of said delay means signal prior to storage in said first storage means and said second signal being provided to enable said first storage means to store said processed delay means signal.

Claim 18

The flow cytometer according to claim 15 wherein said delay means signal occurs between said first and second signals.

Claim 19

The flow cytometer according to claim 15 wherein said threshold means determines the time that said detector means signal is above said threshold, said first signal being provided at a time, related to said delay time, after said detector means signal exceeds said threshold if said time that said detector means signal is above said threshold exceeds a certain minimum time and said first signal being provided at a time related to the time said detector means signal falls below said threshold if said time that said detector means signal is above said threshold does not exceed said certain minimum time.

Claim 20

The flow cytometer according to claim 15 wherein said threshold means provides said second signal a fixed time after said detector means signal falls below said threshold, said delay means signal occurring between said first and second signals.

Claim 21

The flow cytometer according to claim 18 wherein said delay means signal is processed such that the time domain integral is stored in said first storage means.

Claim 22

The flow cytometer according to claim 18 wherein said delay means signal is processed such that the peak value thereof is stored in said first storage means.

Claim 23

The flow cytometer according to claim 10, wherein said processor means includes a plurality of analog signal processors and each analog signal processor stores a signal related to the signal provided thereto, and provides a data signal to said second controller means in response to a poll signal therefrom, each analog processor including amplifying means for amplifying each stored signal to provide said data signal, said amplifying means amplifying said stored signal with one of a first gain or a second gain, said second gain being greater than said first gain, said amplifying means amplifying said stored signal with said second gain unless the signal value amplified with said second gain exceeds a certain value.

Claim 24

The flow cytometer according to claim 21 wherein each analog signal processor provides an associated control signal to said second controller means manifesting the one gain of said amplifying means for the data signal being provided.

Claim 25

The flow cytometer according to claim 22 wherein said second controller means includes an analog to digital converter for converting the analog signal provided thereto to a digital signal, said second controller means digital signal being limited to N bits, at least one of which is said control signal and the remaining ones of which contain the digital signal from said analog to digital converter.

Claim 26

The flow cytometer according to claim 23 wherein each of said analog signal processors has first and second analog signal storage means, said first storage means storing data related to said delayed signal and said second storage means storing data related to the data stored by said first storage means during the time said second controller means polls each analog signal processor.

Claim 27

The flow cytometer according to claim 24 wherein said signal provided for storage to said second storage means is amplified by said amplified means.

Claim 28

The flow cytometer according to claim 21 wherein each of said analog signal processors has first and second analog signal storage means, said first storage means storing data related to said delayed signal and said second storage means storing data related to the data stored by said first storage means during the time said second controller means polls each analog signal processor.

Claim 29

The flow cytometer according to claim 26 wherein said signal provided for storage to said second storage means is amplified by said amplified means.

Claim 30

A flow cytometer for detecting and identifying particles in a fluid, said flow cytometer having means for moving said particles to a detection station means for directing energy at said detection station so that said particles intersect said energy when at said detection station, and a plurality of detectors for providing analog electric signals manifesting different results of each particle intersecting said energy, said flow cytometer comprising: a plurality of analog signal processors, each responsive to one detector signal, each analog signal processor having delay means for providing a delayed signal, which is delayed version of that one detector means signal, first storage means for storing a processed version of said delayed signal, and second storage means for storing, on command, an electric signal related to the signal stored by said first storage means; first controller means responsive to the detector means signal from a selected one of said analog signal processors for determining that a particle is intersecting said energy, said first controller means providing signals to each of said analog signal processors for causing the further processing of said delayed signal and the storage in said first storage means of a value related to said processed delayed signal, and second controller means for providing signals to each of said analog signal processors to cause a value related to the value stored in said first storage means to be stored in said second storage means, said second controller polling each of said analog signal processors to receive, digitize and further process signals related to the values stored in each of said second storage means in order to identify said detected particle, said second controller means providing signals to each of said analog signal processors to cause said value related to the value stored in said first storage means to be stored in said second storage means after completing the polling each of said analog signal processors, said first controller means being disabled from determining that a particle is intersecting said energy until said second controller means provides said signals to each of said analog signal processors causing said value related to the value stored in said first storage means to be stored in said second storage means.

Claim 31

A flow cytometer for detecting and identifying particles in a fluid, said flow cytometer having means for moving said particles to a detection station means for directing energy at said detection station so that said particles intersect said energy when at said detection station, and a plurality of detectors for providing analog electric signals manifesting different results of each particle intersecting said energy, said flow cytometer comprising: a plurality of analog signal processors, each responsive to one detector signal, each analog signal processor having delay means for providing a delayed signal, which is delayed version of that one detector means signal, first storage means for storing a processed version of said delayed signal, and second storage means for storing, on command, an electric signal related to the signal stored by said first storage means; first controller means responsive to the detector means signal from a selected one of said analog signal processors for determining that a particle is intersecting said energy, said first controller means providing signals to each of said analog signal processors for causing the further processing of said delayed signal and the storage in said first storage means of a value related to said processed delayed signal, and second controller means for providing signals to each of said analog signal processors to cause a value related to the value stored in said first storage means to be stored in said second storage means, said second controller polling each of said analog signal processors to receive, digitize and further process signals related to the values stored in each of said second storage means in order to identify said detected particle, said second controller means providing signals to each of said analog signal processors to cause said value related to the value stored in said first storage means to be stored in said second storage means after completing the polling each of said analog signal processors, said first controller means being disabled from determining that a particle is intersecting said energy until said second controller means provides said signals to each of said analog signal processors causing said value related to the value stored in said first storage means to be stored in said second storage means.

Claim 32

The flow cytometer according to claim 28 wherein said first controller means is enabled to detect a detector means signal during the time said second controller means is polling each of said analog signal processors.

Claim 33

The flow cytometer according to claim 29 wherein the further processing of said delayed signal is determining the time domain integral thereof.

Claim 34

The flow cytometer according to claim 30 wherein the further processing of said delayed signal is determining the maximum value thereof.

Claim 35

The flow cytometer according to claim 29 wherein said second controller means provides signals to each of said analog signal processors to cause said value related to the value stored in said first storage means to be stored in said second storage means after completing the polling each of said analog signal processors, said first controller means being disabled from determining that a particle is intersecting said energy until said second controller means provides said signals to each of said analog signal processors causing said value related to the value stored in said first storage means to be stored in said second storage means.

Claim 36

The flow cytometer according to claim 28 wherein said first controller means includes threshold detector means for determining when and how long said detector means signal from said selected one of said analog signal processors exceeds a threshold value.

Claim 39

The improvement according to claim 34 wherein m equals one.

Claim 40

The improvement according to claim 34 wherein said means for determining is a comparator.

Claim 41

The improvement according to claim 36 wherein said comparator has a reference input and a data input, the output of said second amplifier means being coupled to said data input and a signal having a magnitude varying with time being coupled to said reference input.

Claim 42

The improvement according to claim 37 wherein said switch means output signal and switch signal are stored and thereafter provided to said convertor means upon request of said converter means.

Claim 43

The improvement according to claim 38 wherein m equals one.

Claim 44

The improvement according to claim 38 wherein said apparatus for detecting particles further identifies the detected particles and displays information regarding said identified particles as a histogram.

Claim 45

The improvement according to claim 34 wherein said certain value varies in magnitude with respect to time.

Claim 46

A flow cytometer for detecting and identifying various types of particles in a particle containing flowing fluid comprising: means for causing said fluid to flow through a detection station through which is directed energy; a plurality of detector means, each for detecting a different responses of each particle to said energy, each of said detector means providing an electric signal manifesting one response, and each electric signal having an amplitude which varies as a result of the particle type; analog to digital converter means for responding to signals provided thereto for providing a digital signal of n bits manifesting the digital value of an analog signal provided thereto; and a signal processor for each detector means responsive to that detector means signal for making available an analog signal for provision to said analog to digital converter means, each processor including, first and second amplifiers each responsive to the detector means signal provided to that signal processor, said first amplifier having a first gain and said second amplifier having a second gain; said second gain being greater than said first gain; means for determining whether or not said second amplifier signal exceeds a certain value and for providing a switch signal manifesting that said second amplifier signal exceeds said certain value, said means for determining is an analog comparator having a reference voltage input to which a reference voltage is applied to manifest said certain value, said analog comparator further having a signal input coupled to said second input of said switch means, said analog comparator providing a signal manifesting whether or not the voltage at said signal input is greater than said reference voltage and said reference voltage is time varying between a first and second amplitude; and switch means having a pair of inputs, each connected to a different one of said first and second amplifiers, and an output switchably connected with said first input in response to said switch signal manifesting that said second amplifier signal exceeds said certain value, and with said second input in response to said switch signal manifesting that said second amplifier signal does not exceed said certain value, a switch means output signal appearing at said output; means for coupling said switch means output signal and said switch signal from each signal processor, one at a time, to said analog to digital converter means, said analog to digital converter means converting each coupled switch means output signal to a digital signal manifested in n-1 bits, said analog to digital converter means further including the manifestation of said switch signal as the remaining bit of each analog to digital converter means digital signal; and means responsive to said analog to digital converter means digital signals for identifying each detected particle.

Claim 47

A flow cytometer for detecting and identifying various types of particles in a particle containing flowing fluid comprising: means for causing said fluid to flow through a detection station through which is directed energy; a plurality of detector means, each for detecting a different responses of each particle to said energy, each of said detector means providing an electric signal manifesting one response, and each electric signal having an amplitude which varies as a result of the particle type; analog to digital converter means for responding to signals provided thereto for providing a digital signal of n bits manifesting the digital value of an analog signal provided thereto; and a signal processor for each detector means responsive to that detector means signal for making available an analog signal for provision to said analog to digital converter means, each processor including, first and second amplifiers each responsive to the detector means signal provided to that signal processor, said first amplifier having a first gain and said second amplifier having a second gain; said second gain being greater than said first gain; means for determining whether or not said second amplifier signal exceeds a certain value and for providing a switch signal manifesting that said second amplifier signal exceeds said certain value, said means for determining is an analog comparator having a reference voltage input to which a reference voltage is applied to manifest said certain value, said analog comparator further having a signal input coupled to said second input of said switch means, said analog comparator providing a signal manifesting whether or not the voltage at said signal input is greater than said reference voltage and said reference voltage is time varying between a first and second amplitude; and switch means having a pair of inputs, each connected to a different one of said first and second amplifiers, and an output switchably connected with said first input in response to said switch signal manifesting that said second amplifier signal exceeds said certain value, and with said second input in response to said switch signal manifesting that said second amplifier signal does not exceed said certain value, a switch means output signal appearing at said output; means for coupling said switch means output signal and said switch signal from each signal processor, one at a time, to said analog to digital converter means, said analog to digital converter means converting each coupled switch means output signal to a digital signal manifested in n-1 bits, said analog to digital converter means further including the manifestation of said switch signal as the remaining bit of each analog to digital converter means digital signal; and means responsive to said analog to digital converter means digital signals for identifying each detected particle.

Claim 48

The flow cytometer according to claim 42 wherein said reference voltage is a sawtooth wave.

Claim 49

The flow cytometer according to claim 43 wherein means for identifying includes displaying each identified cell in a histogram format.

Claim 50

The flow cytometer according to claim 42 wherein said certain value varies with time.

Claim 51

The flow cytometer according to claim 45 wherein means for identifying includes displaying each identified cell in a histogram format.