Microfluidic Sweeping-Gas Membrane Distillation for PET Tracer Concentration

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Solution Overview

Problem

Current methods for concentrating and formulating positron emission tomography (PET) tracers are hindered by the use of bulky and slow rotary evaporation systems, which require manual intervention and have low evaporation rates, making them unsuitable for time-sensitive applications like preclinical imaging.

Innovation Solution

A microfluidic device with a multi-layer construction, including a sample layer, porous membrane, and gas flow layer, that uses sweeping-gas membrane distillation to achieve rapid and automated concentration of PET tracers, allowing for evaporation rates exceeding 3 mL/min and efficient solvent removal.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of energy

If rotary evaporation systems are used for concentration, then evaporation can be achieved, but the systems are bulky and occupy large space in hot cells

Engineering Contradiction:
Improveevaporation capabilityVSAvoidsystem size
Core Design Contradiction:
Loss of energyVSVolume of stationary object

Solution Approach 1:

The patent replaces the mechanical rotary evaporation system with a microfluidic-based evaporation system that uses capillary forces and controlled fluid flow through porous membranes to achieve solvent removal, eliminating the need for bulky mechanical rotating components and vacuum systems

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

Solution Approach 2:

The invention uses thin porous membrane films as the core evaporation component, allowing large surface area for evaporation in a very compact form factor, replacing the large mechanical evaporator chambers with thin-film-based microfluidic structures

Inventive Principle:
Principle #30Flexible shells and thin films

2Loss of energy

If rotary evaporation is used for concentration, then solvent removal can be achieved, but the process is slow and requires manual intervention

Engineering Contradiction:
Improvesolvent removal capabilityVSAvoidevaporation rate
Core Design Contradiction:
Loss of energyVSProductivity

Solution Approach 1:

The microfluidic system enables continuous flow of sample through the evaporation channel with continuous solvent removal, eliminating the batch-processing nature of rotary evaporation and enabling uninterrupted concentration operations at high speed

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The system uses self-regulating capillary flow through the porous membrane that automatically controls the evaporation rate based on the sample flow rate and solvent vapor pressure, eliminating the need for manual vacuum level assessment and intervention

Inventive Principle:
Principle #25Self-service

3Loss of energy

If solid phase extraction is used for formulation, then solvent removal can be achieved, but dilution with saline makes the probe unusable for preclinical imaging

Engineering Contradiction:
Improvesolvent removal capabilityVSAvoidfinal volume
Core Design Contradiction:
Loss of energyVSQuantity of substance

Solution Approach 1:

The microfluidic device performs localized evaporation directly in the sample channel, concentrating the tracer in situ without requiring subsequent dilution steps, maintaining the ability to deliver precise small volumes suitable for preclinical injection

Inventive Principle:
Principle #3Local quality

4Loss of energy

If direct evaporation of the original sample is used, then formulation can be achieved, but bulky apparatus and manual intervention are required

Engineering Contradiction:
Improveevaporation capabilityVSAvoidapparatus complexity
Core Design Contradiction:
Loss of energyVSDevice complexity

Solution Approach 1:

The patent replaces complex mechanical evaporation apparatus with a simple microfluidic chip that uses inherent capillary forces and controlled fluid dynamics to achieve evaporation, dramatically simplifying the system architecture

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

Solution Approach 2:

The porous membrane acts as an intermediary structure that enables evaporation through its controlled porosity and surface properties, replacing the need for complex vacuum systems and mechanical agitation devices

Inventive Principle:
Principle #24Intermediary (Mediator)

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 microfluidic device enables rapid, automated, and efficient concentration of PET tracers with high recovery rates and the ability to handle a wide range of solvents, significantly reducing the volume of organic solvents to safe levels for injection, thus streamlining the production process and reducing the need for manual handling of radioactive materials.

Implementation Method 1

A microfluidic device with a multi-layer construction, including a sample layer, porous membrane, and gas flow layer, that uses sweeping-gas membrane distillation

Methodology Applied
Scientific EffectMembrane distillation: Semipermeable Membrane

Implementation Method 2

rapid evaporation rates and efficient solvent removal

Methodology Applied
Scientific EffectEvaporation: Evaporation

Implementation Method 3

uses sweeping-gas membrane distillation to achieve rapid and automated concentration

Methodology Applied
Scientific EffectSweeping-gas membrane distillation: Distillation

Data Source

PatentEP3510393B1Method and device for concentration and formulation of radiopharmaceuticals
Publication Date: 2020.11.04 RGT UNIV OF CALIFORNIA
  • EP3510393B1 patent drawingFigure 1~2B
  • EP3510393B1 patent drawingFigure 3
  • EP3510393B1 patent drawingFigure 4

AI summary

A method of formulating or concentrating a radiolabeled molecule or compound includes providing a microfluidic device having a sample layer containing a microfluidic channel formed therein, a porous membrane having a pore size of less than 0.5 µm disposed on the sample layer and covering the microfluidic channel, and a gas flow layer having a gas-carrying channel formed therein, wherein the porous membrane is interposed between the sample layer and the gas flow layer. A fluid containing the radiolabeled molecule or compound is delivered into the microfluidic channel. Heat is applied to evaporate the fluid. A gas is passed through gas-carrying channel to remove evaporated fluid from the microfluidic device.