Hematocrit Control in Mononuclear Cell Collection for Photopheresis

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Solution Overview

Problem

Current therapies for diseases involving mononuclear cells, such as cutaneous T-cell lymphoma and graft-versus-host disease, face challenges with side effects and inefficiencies in delivering targeted treatments, particularly in maintaining optimal hematocrit levels during extracorporeal photopheresis to ensure effective UV irradiation of mononuclear cells.

Innovation Solution

A system utilizing a microprocessor-based controller to adjust and maintain the hematocrit of mononuclear cell products by separating whole blood into red blood cells, plasma, and mononuclear cells, allowing for precise control and adjustment of red blood cell volumes to achieve a target hematocrit, thereby optimizing UV irradiation and minimizing over-irradiation during photopheresis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If whole blood is separated into components and mononuclear cells are collected for photopheresis treatment, then the therapeutic effectiveness is improved, but the hematocrit level becomes difficult to control, leading to suboptimal UV irradiation

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidhematocrit control
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The system incorporates a hematocrit sensor that continuously monitors the hematocrit level of the mononuclear cell product and provides feedback to the controller. The controller automatically adjusts the collection parameters to maintain the hematocrit within the target range of 1-5%, ensuring optimal UV irradiation conditions throughout the photopheresis treatment process.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The system dynamically adjusts collection parameters including flow rate, collection volume, and separation settings based on real-time hematocrit measurements. By changing these parameters adaptively, the system maintains precise hematocrit control while efficiently collecting mononuclear cells for treatment.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If the hematocrit is not precisely controlled during mononuclear cell collection, then the collection process is simpler and faster, but the UV irradiation dosage becomes inconsistent, causing premature apoptosis or under-treatment

Engineering Contradiction:
Improvecollection speedVSAvoidirradiation dosage consistency
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The system pre-establishes target hematocrit ranges (1-5%) and automated control algorithms before the collection process begins. The hematocrit sensor and controller are configured in advance to automatically adjust collection parameters, eliminating the need for manual intervention and ensuring consistent irradiation dosage from the start of treatment.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

Real-time hematocrit monitoring with automated feedback control maintains the hematocrit within the optimal range throughout the collection process. This ensures that the mononuclear cell product receives consistent and appropriate UV irradiation dosage, preventing both premature apoptosis and under-treatment while maintaining efficient collection speed.

Inventive Principle:
Principle #23Feedback

3Device complexity

If manual methods are used to adjust hematocrit levels, then the system complexity is reduced, but the time required to achieve target hematocrit increases and treatment efficiency decreases

Engineering Contradiction:
Improvesystem simplicityVSAvoidtime to achieve target hematocrit
Core Design Contradiction:
Device complexityVSLoss of time

Solution Approach 1:

The system performs self-adjustment of hematocrit levels through automated feedback control. The hematocrit sensor continuously monitors the product, and the controller automatically modifies collection parameters without requiring manual intervention. This self-regulating mechanism rapidly achieves and maintains target hematocrit levels while keeping the operational interface simple for the user.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The automated feedback loop continuously monitors hematocrit and adjusts collection parameters in real-time, eliminating the time-consuming manual adjustment process. The system independently optimizes the collection parameters to achieve target hematocrit quickly, reducing treatment time while maintaining simplicity in operation through automated 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

This approach ensures that mononuclear cells receive the appropriate dose of UV light, preventing premature apoptosis and enhancing the immune response, thereby improving the therapeutic efficacy of the treatment while minimizing side effects.

Implementation Method 1

conveying a volume of whole blood into an inlet region of the chamber for separation into a red blood cell constituent, a plasma constituent, and an interface carrying mononuclear cells

Methodology Applied
Scientific EffectCentrifugal separation: Centrifugal Separation

Data Source

PatentEP3354300B1Systems for collecting mononuclear cells having a suitable hematocrit for extracorporeal photopheresis
Publication Date: 2020.08.05 FENWAL INC
  • EP3354300B1 patent drawingFigure 1
  • EP3354300B1 patent drawingFigure 2
  • EP3354300B1 patent drawingFigure 3

AI summary

A system for collecting MNCs to be treated with irradiation comprises a fluid circuit comprising a product container for receiving a MNC product. The system comprises a separator to work in association with the fluid circuit, the separator comprising a chamber for separation into RBCs, plasma, and an interface carrying MNCs between the RBCs and the plasma. A microprocessor-based controller is in communication with the separator, wherein the controller receives input of a target hematocrit for the MNC product. The controller also receives input for a total volume of whole blood and a number of cycles, and directs the interface and a portion of the RBCs into the product container for a resulting product volume comprising a volume of MNCs and a volume of RBCs. The controller automatically adjusts a RBC volume so that a ratio of RBCs within the MNC product to MNC product equals the target hematocrit.