Nanoneedle Flow Channel for Continuous Intracellular Probing
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Solution Overview
Problem
Current methods for in-vitro cell probing are limited in throughput and efficiency, particularly in facilitating continuous communication with cell interiors for diagnostic and therapeutic applications.
Innovation Solution
A nanoneedle-based apparatus and method that incorporates a flow channel with a constriction to facilitate cell penetration, allowing continuous circulation and controlled delivery or extraction of fluids and reagents within cells, utilizing a nanoneedle formed by depositing material over a sacrificial template and connected to a second flow channel for fluid communication.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a probe such as a patch clamp is inserted into the interior of a cell for in-vitro probing, then cell interior communication is achieved, but throughput and efficiency are limited
Solution Approach 1:
The invention segments the cell processing function into multiple parallel flow channels, each containing nanoneedles. Instead of processing one cell at a time with a single probe, the system divides the workflow into concurrent channels that can handle multiple cells simultaneously, thereby maintaining reliable cell interior communication while dramatically improving throughput.
Solution Approach 2:
The invention replaces the traditional mechanical patch clamp system with a nanoneedle-based system integrated into a fluidic flow environment. This substitution enables automated, high-throughput cell probing by replacing manual or semi-automated mechanical insertion with a streamlined nanoneedle penetration mechanism that operates within a continuous flow system.
2Stability of the object's composition
If cells are immobilized on a substrate for probing, then stable cell positioning is achieved, but continuous circulation and high-throughput operations are hindered
Solution Approach 1:
The invention transitions from a static immobilized cell model to a dynamic circulating cell model. Cells flow continuously through the flow channel and are temporarily positioned near nanoneedles during the probing process, then continue circulating. This dynamic approach maintains adequate positioning stability during measurement while enabling continuous operation and high-throughput processing.
Solution Approach 2:
The flow channel acts as an intermediary that mediates between cell circulation and nanoneedle probing. It provides a controlled environment where circulating cells can be temporarily positioned for interaction with nanoneedles without requiring permanent immobilization, thus maintaining both circulation continuity and probing effectiveness.
3Device complexity
If traditional probing methods are used, then simple apparatus structure is maintained, but controlled delivery and extraction of substances at cellular level is limited
Solution Approach 1:
The nanoneedle system serves multiple functions: it penetrates cell membranes for probing, delivers substances into cells, and extracts substances from cells. This multi-functionality is achieved while maintaining a relatively simple overall apparatus structure, as the same nanoneedle and flow channel infrastructure supports all these operations without requiring separate dedicated systems for each function.
Data Source
AI summary
Disclosed herein are apparatus and methods to perform in-vitro probing of cell interior using a nanoneedle. Some aspects of the present application relate to an apparatus with a vertical nanoneedle disposed in a flow channel, wherein the flow channel is shaped to facilitate immobilization of a cell recirculating in a fluid in the flow channel with the nanoneedle and penetration of the cell membrane with the nanoneedle. Aspects of the present application also provide an integration between the flow channel and a cell sorter to form a medical system that selectively and continuously communicates intracellularly with screened cells of interests.