Kill event optimization

Inventors

SAVAGE, Frederick • Ebersole, Matthew D. • McAda, Daniel • Appleyard, David • Xia, Zheng

Assignees

ABS Global Inc

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Publication Number

US-12092632-B2

Patent

Publication Date

2024-09-17

Expiration Date


Abstract

A method of choosing which undesired cell to destroy in a multi-cell fluorescent event includes detecting fluorescence of cells, converting photons detected in the fluorescence into an analog voltage output signal, and identifying at least two discernable peaks associated with the cells. By looking solely at properties measured within the multi-cell fluorescent event, a decision of which cell to target for elimination can be made. Using this method with large population sizes can result in an effective sex skewed product. The sex skewed product can, for example, be formed from bull semen which is then later used to inseminate cows which results in an increased likelihood of giving birth to female cattle.

Core Innovation

The invention relates to a sexed-semen approach for monitoring and classifying a multi-cell fluorescent event by identifying multiple discernable peaks from a digitized fluorescence signal. Photons detected in the fluorescence of the plurality of cells are converted into an analog voltage output signal, which is digitized so that a raw ADC value can be monitored. The ADC value is used to classify each cell of the plurality as desirable or undesirable, enabling a kill decision tied to the multi-cell event.

An FPGA ADC tracker state machine monitors the raw ADC value and follows a sequence of ADC tracker states including IDLE, RISING, PEAK, FALLING, and VALLEY. A background threshold value gates state transitions, including keeping the tracker in IDLE when the raw ADC value is less than or equal to the background threshold value, and moving between states based on whether the raw ADC value rises above threshold, falls below threshold, or compares to preceding raw ADC values including a recorded peak and valley value.

In a sexed semen system, fluorescence is generated by a fluorescent dye that bounds DNA of the cell, and fluorescence emission events are detected and processed for sex determination. Multi-cell events are detected by the ADC state tracker machine, which classifies each sperm cell as desirable or undesirable, and a kill laser is used for destroying an undesirable sperm cell. Performance modeling and performance testing indicate improvements in purity and product yield relative to a baseline, including purity improvements at the same throughput and further gains at higher throughput.

Claims Coverage

The independent claims cover two inventive features: monitoring a multi-cell fluorescent event using photon-to-analog voltage conversion, FPGA-based ADC state tracking, and cell classification; and a sexed semen system that combines detection optics, fluorescence detection with ADC digitization, multi-cell event classification using an ADC state tracker machine, and a kill laser with kill optics. Across the independent claims, the inventive features repeatedly use the ADC state tracker machine for multi-cell detection and for classifying cells as desirable or undesirable.

Monitoring multi-cell fluorescent events with an FPGA ADC state tracker

Detecting fluorescence in a plurality of cells; converting photons detected in the fluorescence of the plurality of cells into an analog voltage output signal; sending the analog voltage output signal to a field programmable gate array with an analog to digital converter (ADC) state tracker machine; monitoring a raw ADC value of the analog voltage output signal with the ADC state tracker machine; and classifying each cell of the plurality of cells based upon the analog voltage output signal.

Sexed semen system with fluorescence detection, ADC state tracking, and kill laser destruction

A detection laser capable of exciting a sperm cell; a first detection laser lens steering a detection pulse into a sample flow to illuminate the sperm cell; a fluorescent dye that bounds DNA of the cell and produces a fluorescent emission event; a second detection laser lens directing the fluorescent emission event onto a surface of a fluorescence detector; a computer processing unit for determining the sex of the sperm cell based on an output of the fluorescence detector; an ADC converting an analog voltage output signal into a digital output signal; an ADC state tracker machine monitoring a raw ADC value to determine if a multi-cell fluorescent event has occurred and, if so, classifying each sperm cell as desirable or undesirable; and a kill laser for destroying an undesirable sperm cell.

Sexed semen system with ADC state tracking and kill laser with kill lens to a kill spot

A detection laser capable of exciting a sperm cell; a fluorescence detector; a computer processing unit for determining the sex of the sperm cell based on an output of the fluorescence detector; an ADC converting an analog voltage output signal from the fluorescence detector into a digital output signal; an ADC state tracker machine monitoring a raw ADC value to determine if a multi-cell fluorescent event has occurred and, if so, classifying each sperm cell as desirable or undesirable; a kill laser for destroying an undesirable sperm cell; and a kill laser lens to direct a kill beam from the kill laser to a kill spot.

Overall, claim coverage centers on using digitized fluorescence detector outputs with an ADC state tracker machine to detect multi-cell fluorescent events and to classify cells as desirable or undesirable. The system claims additionally require sexed semen detection components and a kill laser, with kill optics in one independent claim, for destroying undesirable sperm cells.

Stated Advantages

Purity improvements, including approximately 2% purity at the same throughput.

Product yield and purity increases at higher throughput.

Documented Applications

Sexed semen product processing, including insemination of cows/female cattle.

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