Microfluidic Sample Probe for Intracellular Material Isolation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for sampling biological cells are prone to damaging the cells and are unable to independently inject and extract materials while maintaining sample isolation, especially for multiplex measurements within complex samples from multiple cells.
Innovation Solution
A sample probe with a distal end configured for penetrating cellular membranes and featuring multiple microchannels for injecting and extracting materials, using isolator fluids to form plugs of intracellular material that are immiscible with the cellular content, allowing for precise and isolated sampling from individual cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If capillaries and pipettes are used to inject materials into cells, then material injection is enabled, but cell damage increases and positioning accuracy decreases
Solution Approach 1:
The patent replaces traditional mechanical pipettes and capillaries with an AFM-based probe system that uses force spectroscopy and controlled mechanical indentation to penetrate cell membranes. This substitution enables precise material injection while minimizing cell damage through controlled force application and accurate positioning feedback.
Solution Approach 2:
The patent uses AFM probe tips that can be repeatedly inserted and withdrawn from cells without significant wear or damage accumulation. The probe tip serves as a reusable copying tool that can perform multiple injection operations on different cells while maintaining consistent performance and minimal cell damage.
2Measurement precision
If AFM probe tips are used for cell penetration, then positioning accuracy improves, but the ability to independently inject and extract materials simultaneously is lost
Solution Approach 1:
The AFM probe is segmented into multiple independent microfluidic channels within its structure. Each channel can independently deliver or extract materials from the cell, allowing simultaneous injection and extraction operations while maintaining the precise positioning capabilities of the AFM system.
Solution Approach 2:
The AFM probe is designed with multi-functionality to perform both injection and extraction operations through its integrated microfluidic channel system. The same probe structure that provides accurate positioning also enables versatile material manipulation functions including simultaneous injection into and extraction from cells.
3Productivity
If multiple samples are extracted from cells, then multiplex measurements are enabled, but sample isolation from other samples is lost
Solution Approach 1:
The patent introduces isolator fluid as an intermediary substance that forms plugs between extracted cell samples in the microfluidic channels. This isolator fluid prevents cross-contamination between samples while allowing multiple samples to be processed simultaneously through the same probe and channel system.
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 minimally invasive sampling and extraction of intracellular material with reduced stress to the cells, allowing for independent injection and extraction of materials from individual cells while maintaining each sample's integrity and isolation from others.
Implementation Method 1
an AFM probe tip or a needle formed from an AFM probe tip has been utilized to extract cell components from cells by inserting the AFM probe tip into the cell
Implementation Method 2
aspirating a sample from the cell, through an opening of the tip, and into a microchannel of the tip
Implementation Method 3
flowing isolator fluid from a second microchannel of the tip into the first microchannel to form a plug of intracellular material defined in part by a boundary between the intracellular material and the isolator fluid
Data Source
AI summary
A sample probe includes a tip including a distal end for penetrating a cellular membrane, an opening located at or proximal to the distal end, and tip microchannels extending through the tip and communicating with the opening; and a body adjoining the tip and including body microchannels, wherein at least one of the body microchannels communicates with at least one of the tip microchannels. A method for sampling intracellular material includes inserting a probe tip through a cellular membrane; aspirating intracellular material from the cell, through an opening of the tip, and into a first microchannel of the tip; flowing isolator fluid from a second microchannel of the tip into the first microchannel to form a plug of intracellular material; and aspirating the plug and the isolator fluid through the first microchannel.