Automated Cell Harvesting Probe for Blood Separation

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Solution Overview

Problem

The existing methods for separating and harvesting blood cells, particularly mononuclear cells, are labor-intensive, prone to variability, and result in cell loss due to manual handling and turbulence during the density gradient separation process.

Innovation Solution

An automated method using a programmable liquid-aspirating and dispensing device that underlays a density gradient solution at the bottom of a centrifugation tube, followed by controlled centrifugation and aspiration to harvest cells, minimizing turbulence and ensuring consistent results.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of substance

If manual layering of blood sample atop density gradient material is used, then cell separation can be achieved, but cell loss occurs due to turbulence during the layering process

Engineering Contradiction:
Improvecell lossVSAvoidmanual layering operation
Core Design Contradiction:
Loss of substanceVSEase of operation

Solution Approach 1:

The patent replaces manual mechanical layering operations with an automated dispenser system that injects density gradient material through a probe. This substitution eliminates human-induced turbulence and ensures consistent, controlled delivery of gradient material without cell loss, directly addressing the contradiction between preventing cell loss and maintaining operational simplicity.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The automated dispenser system performs the layering operation autonomously without requiring manual intervention. The system self-regulates the injection process, ensuring optimal delivery of density gradient material while minimizing cell loss, thereby resolving the contradiction between reducing cell loss and simplifying the operation.

Inventive Principle:
Principle #25Self-service

2Reliability

If manual harvesting of mononuclear cells is performed, then cell collection is achieved, but variability in results occurs between different operators and laboratories

Engineering Contradiction:
Improveuniformity of resultsVSAvoidautomation system complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent replaces manual harvesting operations with an automated aspiration system that uses a programmable dispenser. This substitution eliminates operator variability and ensures consistent harvesting results across different users and laboratories, directly improving reliability while the automated nature of the system manages the complexity through standardized protocols.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The automated system incorporates control mechanisms that monitor and regulate the harvesting process, ensuring consistent results. The programmable nature of the dispenser allows for feedback-based adjustment of aspiration parameters, thereby improving reliability of results while managing system complexity through automated control.

Inventive Principle:
Principle #23Feedback

3Loss of substance

If manual underlaying of density gradient material is used, then cell separation is achieved, but cell loss occurs due to turbulent disturbance during injection

Engineering Contradiction:
Improvecell lossVSAvoidtime-consuming process
Core Design Contradiction:
Loss of substanceVSProductivity

Solution Approach 1:

The patent replaces manual underlaying injection with an automated probe-based dispensing system. This substitution provides controlled, turbulence-free delivery of density gradient material to the bottom of the tube, preventing cell loss while maintaining efficient processing speed, thereby resolving the contradiction between preventing cell loss and maintaining productivity.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The automated system performs the underlaying action in a controlled preliminary step before cell separation, ensuring optimal positioning of density gradient material without causing turbulence. This preliminary automated action prevents cell loss while maintaining efficiency, resolving the contradiction between cell loss prevention and process time.

Inventive Principle:
Principle #10Preliminary action

4Productivity

If automated aspiration of cell layer is performed, then harvesting efficiency is improved, but precise positioning control is required to avoid disturbing the cell layer

Engineering Contradiction:
Improveharvesting efficiencyVSAvoidprobe positioning precision
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent replaces manual probe positioning with an automated programmable dispenser system that precisely controls probe location. This substitution achieves high harvesting efficiency through automated aspiration while ensuring precise positioning control through programmed coordinates, resolving the contradiction between improving productivity and maintaining positioning precision.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The automated system incorporates positioning feedback mechanisms that monitor and adjust probe location in real-time. This feedback control enables high-speed harvesting while maintaining precise positioning accuracy, resolving the contradiction between harvesting efficiency and positioning precision through automated feedback-based control.

Inventive Principle:
Principle #23Feedback

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The automated method significantly reduces variability and increases the efficiency of cell harvesting, achieving comparable or better results than manual methods in terms of cell recovery, viability, and phenotypic characterization.

Implementation Method 1

separating and harvesting blood cells on the basis of their respective densities

Methodology Applied
Scientific EffectDensity gradient separation: Density Gradient

Implementation Method 2

subjected to a relatively low speed (e.g., 200 to 400 g-force) centrifugation

Methodology Applied
Scientific EffectCentrifugal force: Centrifugal Force

Implementation Method 3

This centrifugation step causes differential movement of the different blood cell types within the tube until all of the cells reach a buoyant equilibrium

Methodology Applied
Scientific EffectBuoyant equilibrium: Archimedes' Principle (Buoyancy)

Data Source

PatentEP2129767B1Improved method and apparatus for separating and harvesting cells from a whole blood sample
Publication Date: 2018.09.26 BECKMAN COULTER INC
  • EP2129767B1 patent drawingFigure 1(a)~1(e)
  • EP2129767B1 patent drawingFigure 2(a)~2(f)
  • EP2129767B1 patent drawingFigure 3(a)~3(h)

AI summary

An automated method and apparatus for separating and harvesting cells of interest, e.g., mononuclear cells, in a whole blood sample. The method of the invention uses the aspirating/dispensing probe of an automated sample preparation instrument to underlay a density gradient medium beneath a whole blood sample in a centrifugation tube, and the same probe is used to harvest cells of interest from a cell layer formed in the tube as a result of a centrifugation step. In harvesting cells, the probe is advanced inside the tube by a fixed, predetermined distance at which the probe tip (i.e., its aspiration port) is known to be located at, or within a predetermined distance below, the bottom of the cell layer. A predetermined volume of liquid is then aspirated through the probe tip, whereby most cells of interest (and more than 90% of those cells that can be harvested by a flawless manual method) are removed from the cell layer and collected for analysis. Preferably, the probe is caused to move laterally with respect to the tube during the aspiration of the cell layer, whereby cells offset from the center of the container are readily harvested.