System for flexibly sorting particles

• US 5,199,576 A
• Filed: 04/05/1991
• Issued: 04/06/1993
• Est. Priority Date: 04/05/1991
• Status: Expired due to Term

• Current Assignee: University of Rochester The 518 Hylan BLDG University of Rochester
• Original Assignee: University of Rochester
• Inventors: Leary, James F., Corio, Mark A.
• Primary Examiner(s): Valenza, Joseph E.
• Application Number:
  US07/681,559
• Time in Patent Office: 732 Days
• Field of Search: 209/3.1, 209/564, 209/579, 209/906
• US Class Current: 209/564
• CPC Class Codes: G01N 15/1427 with the synchronisation of components, a time gate for operation of components, or suppression of particle coincidences
• CPC Class Codes: G01N 15/1429 Signal processing
• CPC Class Codes: G01N 15/1459 the analysis being performed on a sample stream
• CPC Class Codes: G01N 15/149 specially adapted for sorting particles, e.g. by their size or optical properties
• CPC Class Codes: G01N 2015/1488 Methods for deciding
• CPC Class Codes: Y10S 209/906 Pneumatic or liquid stream feeding item

Abstract

This invention relates to a method and apparatus for flexibly controlling sorting decisions for a flow cytometer or similar instrument at a purity vs. yield ratio of sorted particles, particularly at high event rates. The system monitors distances between sequential objects to determine if they are in close enough proximity to be within a single resolution unit of the sorting device. The "friend" or "foe" status of neighboring events is considered by this system in dealing with detected "coincident" events. The system operates on information of the desirability to sort the object, i.e. droplet, based upon the properties of the individual object. A storage and retrieval method is provided for making the information available at the time a sort operation based on a sorting logic condition is performed. Accordingly, an easily reconfigurable mode of operation control is provided to allow customized sorting strategies, based on the needs of individual applications or experiments. This system may be included as an integral part of a flow cytometer/cell sorter or similar instrument and may also be provided as an outboard module to such systems.

Claims

1. A system for sorting particles comprising:

a measurement unit which measures selected parameters of moving particles and generates a respective trigger signal in response to the passage of selected particles by a selected point and respective detector signals pertaining to selected parameters of the particles;

an overlap detection circuit responsive to successive trigger signals to generate respective overlap signals in response to time separation of trigger signals by less than selected intervals; and

a sorter responsive to the trigger, detector and overlap signals to generate respective sorting signals for sorting the particles at a selected yield/purity ratio which includes intermediate values between maximum yield and maximum purity.

2. A system as in claim 1 further comprising:

an event timing unit responsive to the trigger signal to measure a predetermined time delay interval pertaining to the time for passage of the particles from said selected point to a selected sorting point and to generate an event timing signal at the end of the predetermined time delay interval; and

a sort pulse timing control unit responsive to said event timing signal for applying the respective sorting signals to the particles.

3. A system for sorting particles as in claim 2 in which the sorter comprises sort value storage means for receiving the detector and overlap signals and for storing the detector and overlap signals received before and during the predetermined time delay interval;

sort value storage control means controlling the storing of the detector and overlap signals in the sort value storage means by updating an availability level counter; and

sort pulse decision logic means receiving the detector, overlap signals and availability level counter from the sort value storage means and producing the logic signal whenever a selected combination of the detector, overlap and availability level counter correspond to the selected yield/purity ratio during said predetermined delay interval.

4. A system as in claim 3 further comprising:

a sort pulse definition unit for generating the shape of the respective sorting signal to be applied to the particles.

5. A system for sorting particles comprising:

a source of detection signals for respective particles generated in response to the respective particle passing a selected point;

measurement means for measuring selected parameters of the respective particles to generate respective individual sort decisions and for generating a respective trigger signal in response to said detection signals;

overlap detecting means responsive to successive trigger signals for generating a respective overlap signal in response to time separation between the successive trigger signals of less than selected intervals;

event timing means responsive to the trigger signal to measure a predetermined delay in time pertaining to the passage of the respective particles from the selected point to a selected sorting point and to generate an event timing signal after the determined delay in time; and

sort means for sorting the respective particles responsive to the respective individual sort decisions, respective overlap signals and event timing signal to apply a sort pulse to the respective particle whenever a selected combination of individual sorting decisions and overlap signal occurs during said predetermined delay in time.

6. A system as in claim 5 in which said sort means further comprises:

sort value storage means for storing successive respective individual sort decisions and successive respective overlap signals before and during the predetermined delay in time; and

sort control means for controlling the successive respective individual sort decisions and the successive respective overlap signals in the sort value storage means and for retrieving the successive respective individual sort decisions and overlap signals from the sort value storage means.

7. A system as in claim 6 further comprising:

a sort pulse definition means for generating a value of the sort pulse.