Parallel pulse processing and data acquisition for high speed, low error flow cytometry

• US 5,150,313 A
• Filed: 04/12/1990
• Issued: 09/22/1992
• Est. Priority Date: 04/12/1990
• Status: Expired due to Term

• Current Assignee: Lawrence Livermore National Security LLC (Government of the United States of America)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: van den Engh, Gerrit J., Stokdijk, Willem
• Primary Examiner(s): Lall, Parshotam S.
• Assistant Examiner(s): AUCHTERLONIE, THOMAS
• Application Number:
  US07/508,226
• Time in Patent Office: 894 Days
• Field of Search: 364/486, 364/569, 364/555, 364/178, 364/179, 364/200, 364/900, 364/550, 395/250, 395/275, 395/550, 395/725, 395/800
• US Class Current: 702/79
• CPC Class Codes: G01N 15/1456 without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals
• CPC Class Codes: G01N 2015/1477 Multiparameters
• CPC Class Codes: G06F 5/06 for changing the speed of data flow, i.e. speed regularising or timing, e.g. delay lines, FIFO buffers; over- or underrun control therefor G06F7/78 takes precedence

Abstract

A digitally synchronized parallel pulse processing and data acquisition system for a flow cytometer has multiple parallel input channels with independent pulse digitization and FIFO storage buffer. A trigger circuit controls the pulse digitization on all channels. After an event has been stored in each FIFO, a bus controller moves the oldest entry from each FIFO buffer onto a common data bus. The trigger circuit generates an ID number for each FIFO entry, which is checked by an error detection circuit. The system has high speed and low error rate.

Claims

1. Apparatus for pulse processing and data acquisition from a plurality of detectors generating asynchronous event pulses from a single event, comprising:

a plurality of parallel input channels, each of which receives one of the event pulses from a respective detector;

pulse digitization means in each channel for digitizing the event pulse received in the channel;

a channel FIFO buffer in each channel connected to the respective pulse digitization means;

a common data bus connected to all the FIFO buffers;

central control means external to the channels connected to each channel for providing a synchronizing timing signal to the respective pulse digitization means in each channel in response to a start signal from at least one of the channels to synchronize pulse digitization in each channel with detection of the event by the respective detector and to digitize each pulse on each channel substantially immediately after the pulse is input on the channel;

a bus controller connected to the data bus and to the control means for transferring correlated data from the FIFO buffers to the data bus following an actuation signal from the control means, the transferred data being correlated to the event.

2. The apparatus of claim 1 wherein the pulse digitization means in each channel comprises:

a pulse sample/hold module;

an analog-to-digital converter (ADC) connected to the pulse sample/hold module and having a track/hold input section;

wherein the pulse sample/hold module and ADC are operated in a staggered timing relationship by triggering the pulse sample/hold module on a gate pulse and triggering the track/hold input section of the ADC substantially immediately following the gate pulse to the pulse/sample hold module.

3. The apparatus of claim 2 wherein the control means further comprises an event ID number generation means for providing an event ID number for each event stored in the FIFO buffers.

4. The apparatus of claim 3 wherein the pulse sample/hold modules and analog-to-digital converters each further comprise a local FIFO buffer to transfer the event ID number from the control means to the channel FIFO buffer.

5. The apparatus of claim 1 wherein the control means further comprises:

minimum event separation generation means;

minimum event width generation means.

6. The apparatus of claim 5 wherein the control means further comprises minimum trigger width generation means.

7. The apparatus of claim 1 wherein the control means further comprises an event ID number generation means for providing an event ID number for each event stored in the FIFO buffers.

8. The apparatus of claim 7 further comprising error detection means connected to the data bus for detecting the event ID numbers in the FIFO buffers.

9. The apparatus of claim 1 wherein the control means further comprises a reset timer.

10. The apparatus of claim 1 wherein the control means further comprises blocking means for disabling the control means when a data correlation error signal is received by the blocking means and until a restart signal is received.

11. The apparatus of claim 1 wherein the control means comprises:

a comparator having its input connected to a start signal from the channels;

a leading edge detector having its input connected to the output of the comparator;

an input gate having an input connected to the output of the leading edge detector and another input connected to a blocking signal;

a first flip/flop having its set input connected to the output of the input gate;

a second flip/flop having its set input connected to the output of the first flip/flop and its clear input connected to the output of the comparator;

a minimum event separation timer connected to the clear input of the first flip/flop;

a minimum event width timer having an input connected to the output of the second flip/flop;

an OR gate having a first input connected to the output of the second flip/flop and a second input connected to the output of the minimum event timer and its output connected to the input of the minimum event separation timer.

12. The apparatus of claim 11 further comprising:

a minimum trigger width timer connected to the output of the first flip/flop;

an OR gate having an input connected to the comparator and a second input to the output of the minimum trigger width timer and its output to the clear input of the second flip/flop.

13. The apparatus of claim 1 further comprising error detection means connected to the data bus for detecting correlation errors in data transferred from the FIFO buffers to the data bus.

14. The apparatus of claim 13 wherein the error detection means further comprises a reset means connected to the control means and bus controller.

15. The apparatus of claim 1 wherein the FIFO buffer comprises a first buffer for storing the event ID number and a second buffer in parallel with the first buffer for storing digitization event data.

16. The apparatus of claim 1 wherein the control means further comprises:

trigger signal generation means;

a digital delay line connected to the trigger signal generation means for providing measured time delays to gating signals to the channels.

17. The apparatus of claim 1 further comprising an address bus connected from the bus controller to each FIFO buffer.

18. A method for pulse processing and data acquisition from a plurality of asynchronous pulses generated by a single event from a plurality of detectors comprising:

inputting an event pulse onto each of a plurality of parallel input channels;

digitizing each event pulse on each channel substantially immediately after inputting the pulse on the channel and synchronously with detection of the event by an associated detector;

storing the digitized event in a FIFO buffer on each channel;

transferring correlated stored digitized event data about a single event from all the FIFO buffers onto a common data bus.

19. The method of claim 18 further comprising generating an event ID number for each event pulse and storing the event ID number in the FIFO buffer.

20. The method of claim 19 further comprising comparing all event ID numbers from a single event on the data bus.

21. The method of claim 18 further comprising checking that a single event data entry is transferred to the data bus from every channel.

22. The method of claim 18 further comprising generating a minimum event separation and a minimum event width.

23. The method of claim 22 further comprising generating a minimum trigger width.

24. The method of claim 18 further comprising digitizing successive event pulses on each channel by initiating pulse sample and holding of a succeeding pulse while performing analog-to-digital conversion of a preceding pulse when the succeeding pulse occurs prior to completion of analog-to-digital conversion of the preceding pulse.

25. Apparatus for generating a trigger pulse, comprising:

a comparator having its input connected to a start signal;

a leading edge detector having its input connected to the output of the comparator;

an input gate having an input connected to the output of the leading edge detector and another input connected to a block signal;

a first flip-flop having its set input connected to the output of the input gate;

a second flip-flop having its set input connected to the output of the first flip/flop and is clear input connected to the output of the comparator;

a minimum event separation timer connected to the clear input of the first flip/flop;

a minimum event width timer having an input connected to the output of the second flip/flop;

an OR gate having a first input connected to the output of the second flip/flop and a second input connected to the output of the minimum event timer and its output connected to the input of the minimum event separation timer;

wherein the outputs of the second flip/flop, the OR gate, and the minimum event width timer can be used as trigger pulses.