Pulsatile Microdialysis Probe for Rapid Drug Concentration Detection

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Solution Overview

Problem

Conventional continuous flow microdialysis methods suffer from poor time resolution and low sampling efficiency, making it difficult to accurately measure rapidly changing drug concentrations and recover drugs in short time frames, especially in biological systems where processes can occur during sample preparation.

Innovation Solution

The implementation of pulsatile microdialysis, where the dialysate is pumped into a microdialysis probe, allowed to rest for a specified time, and then flushed out in a single pulse for analysis, allowing for improved time resolution and increased recovery fraction of the drug by optimizing the resting time and sample volume.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If continuous flow microdialysis is used to sample drug concentrations, then a continuous stream of dialysate is obtained for analysis, but the time resolution is poor and sampling efficiency is low

Engineering Contradiction:
Improvetime resolutionVSAvoidsampling efficiency
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent applies periodic action by switching from continuous flow to pulsatile flow, where dialysate is pumped into the probe in discrete pulses followed by rest periods. This periodic pumping pattern allows the dialysate to remain stationary in the probe during the rest period, enabling diffusion of drug molecules into the dialysate without being continuously washed away, thereby improving both time resolution and sampling efficiency

Inventive Principle:
Principle #19Periodic action

2Quantity of substance

If high perfusion flow rates are used in continuous flow microdialysis, then sample volume is increased for analysis, but the recovery fraction of drug decreases and time resolution worsens

Engineering Contradiction:
Improvesample volumeVSAvoidrecovery fraction
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The pulsatile flow method uses periodic pumping with distinct pump and rest phases. During the rest period, the dialysate remains stationary allowing efficient drug diffusion and high recovery fraction. During the pump phase, the dialysate is rapidly flushed to collect sufficient sample volume. This temporal separation resolves the contradiction between sample volume and recovery fraction

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The method performs preliminary action by allowing drug molecules to diffuse into the stationary dialysate during the rest period before the pump phase begins. This pre-loading of the dialysate with drug molecules ensures high recovery fraction, while the subsequent rapid pumping ensures sufficient sample volume is collected for analysis

Inventive Principle:
Principle #10Preliminary action

3Quantity of substance

If long sampling times are used in continuous flow microdialysis, then sufficient sample volume is obtained, but the ability to capture rapid concentration changes is lost

Engineering Contradiction:
Improvesample volumeVSAvoidtime resolution
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The pulsatile flow method uses short rest periods followed by rapid pumping phases. The rest period allows drug diffusion into the dialysate, while the subsequent rapid pump phase quickly collects the sample. This creates a short total sampling cycle that captures rapid concentration changes while still obtaining sufficient sample volume through the high-flow pump phase

Inventive Principle:
Principle #19Periodic action

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

Pulsatile microdialysis provides enhanced time resolution and increased sampling efficiency, enabling the detection of low concentrations and rapid changes in drug concentrations, and allows for the determination of free drug concentrations and permeability through the probe wall, overcoming the limitations of continuous flow microdialysis.

Implementation Method 1

a drug or other material of interest passively diffuses into the dialysate from the surrounding medium

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentUS8679052B2Method for accurately determining concentrations of diffusible materials
Publication Date: 2014.03.25 PHYSICAL PHARMACEUTICA LLC
  • US8679052B2 patent drawing
  • US8679052B2 patent drawing
  • US8679052B2 patent drawing

AI summary

The invention provides an improved microdialysis method for determining the free concentration of an agent or drug (defined as the concentration of agent that is dissolved and free to diffuse, and not undissolved or precipitated, complexed, bound, included in micelles or microemulsions, etc.).In addition. the invention provides such a method under conditions in which the properties of the microdialysis probe may change.Further, the invention provides a method for determining the permeability of a diffusible agent through the probe wall.The invention also provides a method for determining the rate of change of concentration of an agent in a medium.