Mononuclear Cell Collection Reducing Plasma Interference
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Solution Overview
Problem
During photopheresis, the presence of residual plasma interferes with the delivery of UV-A light to mononuclear cells, as it absorbs or attenuates the light energy, especially in cases with elevated bilirubin levels or medications like mycophenolate mofetil and cyclosporine, which cause hyperlipidemia, reducing the effectiveness of the treatment.
Innovation Solution
A method and system for collecting mononuclear cells with a reduced volume of residual plasma by concentrating the cells and adding a crystalloid solution, such as saline, to achieve a plasma volume of less than or equal to 25% and a hematocrit of less than or equal to 2%, thereby minimizing plasma interference and ensuring effective light delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If whole blood is separated into constituent components and MNCs are collected, then mononuclear cells can be obtained for photopheresis treatment, but residual plasma remains in the MNC product which interferes with UV-A light delivery
Solution Approach 1:
The patent applies extraction by removing plasma from the MNC product through a washing step. The system separates and removes plasma containing interfering substances (proteins, lipids, bilirubin) while retaining the mononuclear cells, thereby eliminating the harmful interference with UV-A light delivery during photopheresis treatment
Solution Approach 2:
The patent uses a crystalloid solution as an intermediary medium to replace plasma in the MNC product. This crystalloid suspension serves as a mediator that does not absorb UV-A light, allowing effective light delivery while maintaining cell suspension and transport functionality
2Illumination intensity
If plasma volume is reduced in the MNC product, then UV-A light delivery is improved, but the concentration of mononuclear cells increases requiring dilution
Solution Approach 1:
The patent applies parameter changes by adjusting the plasma volume parameter in the MNC product to less than 50 mL through removal, and then adjusting the crystalloid volume to achieve optimal cell concentration. This dual parameter adjustment ensures both improved light penetration and appropriate cell dosage for treatment
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 reduced plasma volume allows for increased UV-A light dose delivery to mononuclear cells, enhancing the treatment efficacy by achieving at least twice the intended UV-A light dose, as demonstrated by increased lymphocyte apoptosis levels post-treatment.
Implementation Method 1
separating mononuclear cells from whole blood by introducing the whole blood into a centrifuge chamber wherein the whole blood is separated into its constituent components based on the size and densities of the different components
Implementation Method 2
exposed to ultraviolet light, and returned to the patient. The activated 8-methoxypsoralen crosslinks with the DNA in the exposed MNCs
Implementation Method 3
adding a crystalloid solution to the concentrated mononuclear cells so that the volume% of plasma is less than or equal to 25%
Data Source
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AI summary
A method for obtaining MNCs is set forth. The method includes: separating mononuclear cells from a biological fluid that includes red blood cells, plasma and platelets and collecting a targeted number of mononuclear cells in a suspension including plasma and residual red blood cells and platelets; concentrating the separated mononuclear cells; removing plasma from the concentrated mononuclear cells until the amount of residual plasma remaining with the concentrated mononuclear cells reaches a pre-determined volume; and adding a crystalloid solution to the concentrated mononuclear cells. Related apparatus and resultant MNC products are also disclosed.