Single-sheath microfluidic chip

Inventors

Xia, Zheng • Kamalakshakurup, Gopakumar

Assignees

ABS Global Inc

Abstract

Microfluidic devices and methods for focusing components in a fluid sample are described herein. The microfluidic devices feature a microfluidic chip having a micro-channel having a constricting portion that narrows in width, and a flow focusing region downstream of the micro-channel. The flow focusing region includes a positively sloping bottom surface that reduces a height of the flow focusing region and sidewalls that taper to reduce a width of the flow focusing region, thereby geometrically constricting the flow focusing region. The devices and methods can be utilized in sex-sorting of sperm cells to improve performance and increase eligibility.

Core Innovation

The disclosed invention is a microfluidic chip for flowing a sample fluid mixture comprising sperm cells through a sample micro-channel and a downstream micro-channel having an intersection region for introducing sheath fluid, followed by a constricting portion and a second straight portion configured to provide laminar flow. The constricting portion narrows in width only and only geometrically compresses the sample fluid mixture. A downstream flow focusing region includes a positively sloping bottom surface and tapering sidewalls that reduce a height and reduce a width of the flow focusing region, thereby geometrically constricting the flow focusing region.

In operation as described, sheath fluid compresses the sample fluid mixture so that the sperm cells become surrounded by sheath fluid and compressed into a thin, centrally located stream within the downstream micro-channel. The geometry is arranged so that sperm cells are uniformly orienting and positioned for interrogation and selective action, including centralization/focusing at or near the center of the downstream micro-channel. This creates a focused thin stream in which sperm are aligned for downstream interrogation/sorting.

For producing gender-skewed sperm cells, the chip is used with downstream determination of a chromosome type of sperm cells, where each sperm cell is either a Y-chromosome-bearing sperm cell or an X-chromosome-bearing sperm cell. Based on the determination, the method sorts Y-chromosome-bearing sperm cells from X-chromosome-bearing sperm cells to produce a fluid comprising gender-skewed sperm cells that are predominantly Y-chromosome-bearing. The document further describes an interrogation region and optional interrogation/sorting mechanisms, including radiation-based detection and laser kill/ablation of X-bearing sperm cells, and notes broader applicability to other particle/cell separations.

Claims Coverage

The partial content includes three independent claims (microfluidic chip for focusing/orienting sperm; method of focusing particles; method of producing gender-skewed sperm). Across these independent claims, the core inventive features are centered on a dual-stage flow-focusing architecture with sheath-fluid intersection compression, a downstream width-only constricting portion providing laminar flow, and a positively sloping bottom surface with tapering sidewalls for geometric constriction and re-orientation/focusing.

The independent claims cover a microfluidic chip architecture that uses an intersection-based sheath-fluid introduction to compress and position sperm cells, followed by a downstream width-only constricting portion under laminar flow, and a second flow focusing region defined by a positively sloping bottom surface and tapering sidewalls to further geometrically constrict and re-orient/focus sperm. The method claim extends this focused, thin stream to chromosome-type determination of sperm cells and sorting to produce gender-skewed sperm predominantly containing Y-chromosome-bearing cells.

Stated Advantages

Documented Applications