Tissue sample processing system and associated methods
Inventors
Gale, Bruce K. • Carrell, Douglas T. • Murphy, Kristin • Hotaling, Jim • Son, Jiyoung
Assignees
University of Utah • University of Utah Research Foundation Inc
Publication Number
US-11708556-B2
Publication Date
2023-07-25
Expiration Date
2035-10-20
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Abstract
A tissue sample processing system and associated methods is disclosed and described. The tissue sample processing system (100) can include a microfluidic separating system (110). The microfluidic separating system (110) can include a fluid channel to receive a carrier fluid (104) and a tissue sample (102), and a plurality of outlets. Flow of the carrier fluid (104) and the tissue sample (102) in the fluid channel can facilitate segregation of materials in the tissue sample (102) based on size into a plurality of size fractions, such that each one of the plurality of outlets receives a different size fraction of the materials in the tissue sample. In addition, the sample processing system (100) can comprise a cryopreservation system (120) associated with at least one of the plurality of outlets to freeze the material in the tissue sample (102) associated with the at least one of the plurality of outlets.
Core Innovation
The invention concerns a tissue sample processing system that incorporates a microfluidic separating system with a fluid channel and multiple outlets. This microfluidic system receives a carrier fluid and a tissue sample, such as a sperm or semen sample, and uses controlled flow within the channel to segregate materials in the sample by size into a variety of size fractions, with each outlet collecting a different fraction. The system is specifically designed to enable separation of sperm cells, including non-motile sperm, from other cells and debris based on physical characteristics such as size and shape, using principles like inertial lift and Dean drag in spiral or straight microfluidic channel configurations.
A key feature of the system is its compatibility with downstream processing, notably sorting and concentrating subsystems. These components can further separate or concentrate specific cell types from each outlet and sort selected aliquots of sperm, including as few as a single non-motile sperm cell per aliquot. The system may also integrate a cryopreservation unit to freeze specific material (such as enriched sperm fractions) directly from the sorting or concentrating systems or from individual outlets, allowing multiple aliquots to be stored and thawed independently.
The problem addressed is the inefficiency and inaccuracy of current manual and bulk tissue-based methods for isolating and recovering sperm, particularly non-motile sperm from men with non-obstructive azoospermia undergoing procedures like mTESE. Existing methods often result in sperm being lost after cryopreservation, require labor-intensive manual searches, allow only one thawing event for therapeutic use, and lack the capability to efficiently separate non-motile sperm from tissue and blood cell contaminants. The disclosed system overcomes these limitations with automated, size and shape-based segregation, and improved aliquoting and preservation steps that do not depend on sperm motility or reagents.
Claims Coverage
There is one independent inventive feature, with several dependent features, covering the main concepts of the microfluidic separation system and associated sample processing.
Microfluidic separation of sperm sample into size and shape fractions via a fluid channel with multiple outlets
The core inventive feature is a method of separating sperm cells by obtaining a microfluidic separating system comprising a fluid channel and a plurality of outlets. The sperm sample is disposed in the fluid channel, and flow of the sample within the channel facilitates segregation of materials within the sperm sample based on both size and shape into multiple size and shape fractions. Each individual outlet collects a different size and shape fraction, allowing for physical separation of cell populations, such as non-motile sperm, motile sperm, red blood cells, or other specific cell types, without reliance on motility or labeling.
The claims protect a method for separating sperm cells within a microfluidic separating system configured to distinguish material based on size and shape, enabling independent collection of different cell fractions at distinct outlets. Additional dependent claims specify features like spiral-configured channels, cross-flows, sorting and aliquoting of non-motile sperm, cryopreservation steps, and the option to operate without added reagents.
Stated Advantages
Automated and microscale flow reduces human error, time, and required skill compared to manual microscopic sperm separation.
Multiple aliquots can be created, stored, and thawed individually, enhancing IVF outcomes over bulk cryopreservation.
The system increases recovery rates of sperm cells compared to current cryopreservation methods.
Sperm cell quality is preserved, as no labeling, enzymes, or lysis are involved in the process.
The closed microfluidic system promotes sterility, minimizes sample loss, and prevents contamination.
The system does not rely on sperm motility, allowing for isolation of non-motile sperm not possible with previous technologies.
Automation enables efficiency, consistency, and time savings for clinicians in sample processing.
Documented Applications
Isolation and enrichment of sperm from testicular tissue, particularly for patients with male infertility, including non-obstructive azoospermia.
Preparing and aliquoting sperm samples for use in assisted reproductive technologies (ART), such as in vitro fertilization (IVF).
Cryopreservation of sperm or other isolated cell types in discrete aliquots for future use in fertility procedures.
Isolation of other rare or sparse cell types from testicular tissue, such as spermatogonial stem cells and sperm precursor cells, for research or therapeutic purposes.
Purification and separation of normal (euploid) sperm cells from abnormal (aneuploid) sperm cells for reproductive selection.
Use in reproductive research, including molecular analysis and gene expression studies on isolated cell populations from testicular tissue.
Separation of sperm and removal of white blood cells or red blood cells from semen samples, improving sample quality for ART.
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