Pipette Tip With Orifice Membrane for Single-Cell Impedance Analysis
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Solution Overview
Problem
Current pipette systems cannot effectively detect and analyze particles, such as cells, within fluids, especially at the single-cell level, due to limitations in design and sensor placement, which affects the accuracy and sensitivity of impedance measurements.
Innovation Solution
A pipette tip system with a restricted tip design featuring a thin membrane with a small orifice, optimized for single-cell dispensing and analysis, incorporating electrodes outside and inside the tip to establish an electric field for impedance-based detection using a time-resolved impedance analyser, allowing for precise measurement of particle characteristics without requiring precise sensor placement.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a standard pipette tip design is used, then fluid handling precision is maintained, but particle detection capability is lost
Solution Approach 1:
The patent combines a pipette tip with a Coulter counter sensor system into an integrated device. The tip incorporates an orifice with electrodes positioned to detect particles passing through, merging fluid handling with particle analysis capabilities in a single tool.
Solution Approach 2:
The pipette tip is designed to perform multiple functions: fluid aspiration and dispensing like a standard pipette, plus particle detection and analysis through the integrated impedance sensor system, making it a multi-functional laboratory tool.
2Measurement precision
If electrodes are placed close to the orifice for sensitive detection, then measurement sensitivity improves, but device complexity and manufacturing difficulty increase
Solution Approach 1:
The patent positions electrodes at specific locations relative to the orifice - one electrode inside the tip and one outside - creating localized sensing zones that optimize detection sensitivity while maintaining manufacturable geometry.
Solution Approach 2:
The sensor design uses asymmetric electrode placement with different electrode configurations inside versus outside the tip, optimizing the electric field distribution for particle detection while simplifying manufacturing compared to symmetric designs.
3Productivity
If the orifice is made small for single-cell dispensing, then cell isolation capability improves, but particle detection sensitivity decreases
Solution Approach 1:
The patent compensates for the weak signal from small orifice passage by using a high-impedance measurement system with sensitive electronics that can detect the small impedance changes caused by particles passing through the restricted orifice.
Solution Approach 2:
The system performs preliminary impedance measurements to characterize particles before dispensing, allowing selection and verification of single cells for isolation and dispensing through the small orifice.
4Productivity
If a restricted tip design with thin membrane is used, then single-cell isolation capability improves, but dead volume increases
Solution Approach 1:
The tip design segments the internal volume with a restricted orifice section, creating a defined sensing zone that minimizes dead volume while maintaining single-cell isolation capability through the membrane structure.
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 system enables reliable and accurate single-cell dispensing and analysis, improving signal-to-noise ratio and sensitivity, making it suitable for applications in cell biology and medicine by minimizing dead volume and allowing for flexible electrode placement.
Implementation Method 1
characterizing dielectric particles in a fluid in term of number and size... When an electrical current is applied between the two electrodes, most of the electrical resistance or impedance is in the orifice. If a cell passes through the orifice, it displaces an equivalent volume of saline resulting in an increase in impedance.
Implementation Method 2
Means to detect particles in a fluid were first described in the Coulter counter principle (US2656508A). This principle allows for characterizing dielectric particles in a fluid in term of number and size.
Data Source
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AI summary
The present invention relates to a pipette tip comprising a thin holed membrane at its distal end, which is designed to be adapted with a system comprising at least an impedance analyser and a fluidic actuator to perform the dispensing and analysis of particles comprised within a conductive medium by exploiting the Coulter counter principle. The pipette tip can comprise attached or floating electrodes at its internal or external side for creating an electrical circuit. Also disclosed therein is a dispensing and analysis system, methods of using thereof and pipette tip's manufacturing methods.