SPME Micro-Syringe Plunger for In Vivo Non-Polar Analyte Extraction
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Solution Overview
Problem
Existing techniques for determining in vivo concentrations of analytes, such as microdialysis and push-pull, are limited in sensitivity for non-polar compounds due to bonding to tissue matrices, leading to reduced sensitivity and quantitative analysis issues.
Innovation Solution
A micro-syringe with a plunger coated by solid-phase micro-extraction (SPME) coating, allowing for in vivo extraction of analytes without solvent activation, using hydrophilic-lipophilic balance (HLB) microparticles in a polyacrylonitrile (PAN) binder, which can be inserted into a sample matrix to adsorb and withdraw analytes for analysis by LC-MS/MS or MOI-MS/MS.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If microdialysis or push-pull techniques are used to extract analytes from tissue, then the technique can measure compounds in free form, but the sensitivity for non-polar compounds is reduced due to bonding to tissue matrices
Solution Approach 1:
The patent introduces an SPME coating as an intermediary phase between the tissue matrix and the analysis system. This coating selectively binds non-polar compounds through adsorption, preventing them from bonding to the tissue matrix while still allowing extraction. The SPME phase acts as a mediator that captures non-polar analytes that would otherwise be lost to tissue binding, thereby improving sensitivity without compromising the ability to measure free compounds.
Solution Approach 2:
The patent changes the extraction mechanism from liquid-phase extraction (microdialysis/push-pull) to solid-phase extraction (SPME). This parameter change in the extraction phase state allows for selective adsorption of non-polar compounds onto the SPME coating, significantly improving sensitivity for these analytes while maintaining compatibility with tissue sampling.
2Productivity
If SPME coating is exposed to solvent for activation, then the extraction efficiency is improved, but solvent exposure increases which may cause tissue damage or contamination
Solution Approach 1:
The patent performs solvent activation of the SPME coating as a preliminary action during device manufacturing, before the device is used for tissue sampling. The SPME coating is exposed to solvent in a controlled manufacturing environment to activate and condition the extraction phase, then the device is ready for use without requiring further solvent exposure during actual tissue analysis. This eliminates the need for solvent exposure at the tissue sampling site, preventing tissue damage while maintaining extraction efficiency.
Solution Approach 2:
The patent separates the SPME coating activation process from the tissue sampling process. The activation step is performed as a separate preliminary operation during device preparation, while the tissue sampling step uses the pre-activated coating without additional solvent. This segmentation allows the harmful solvent exposure to be confined to manufacturing rather than clinical use.
3Object-affected harmful factors
If fine-needle aspiration biopsy is used to reduce sampling site trauma, then the area of infection-prone site is reduced, but the technique can only extract small tissue portions limiting metabolomics analysis
Solution Approach 1:
The patent creates a multi-functional device that combines fine-needle aspiration capability with SPME extraction capability. The same minimally invasive needle can both extract tissue samples and simultaneously perform metabolite extraction via the SPME coating. This universal device achieves both goals: minimal tissue trauma from the fine needle while providing sufficient analyte quantity through the SPME enrichment capability for comprehensive metabolomics analysis.
Solution Approach 2:
The patent changes the extraction mechanism from relying on large tissue volume to relying on SPME enrichment. Instead of needing large tissue samples, the SPME coating concentrates analytes from small tissue portions, enabling metabolomics analysis with minimal tissue input. This parameter change in the extraction approach allows small fine-needle samples to provide sufficient analyte quantity.
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
Enables high selectivity and sensitivity for both polar and non-polar compounds, minimizing tissue damage and solvent exposure, facilitating untargeted metabolomics and targeted analyte monitoring with minimal invasiveness.
Implementation Method 1
The extraction coating includes adsorptive particles. Exposure of the SPME device directly into a matrix or into its headspace, for a certain period of time, extracts and enriches analytes contained in the sample matrix. The SPME process is governed by the partitioning of analytes from the matrix onto or into the extraction phase, and extraction efficiency of an analyte depends on the analyte's affinity toward the adsorptive particles present in the extraction coating.
Implementation Method 2
The plunger is sized to fit the internal diameter of the micro-syringe body to draw a liquid into the micro-syringe body when the plunger is moved from the extended position to the internal position.
Data Source
AI summary
A micro-syringe for inserting into a sample matrix. The micro-syringe includes a micro-syringe body having an orifice at an insertion end; and a plunger at least partially coated with a solid-phase micro-extraction (SPME) coating. The plunger is longitudinally movable between an internal position and an extended position. When the syringe is inserted into the sample matrix, the extraction phase is shielded from the sample matrix by the micro-syringe body when the plunger is in the internal position, and at least a portion of the extraction phase extends past the orifice and is exposed to the sample matrix when the plunger is in the extended position. The plunger is sized to fit the internal diameter of the micro-syringe body to draw a liquid into the micro-syringe body when the plunger is moved from the extended position to the internal position.