Well-Plate Expansion Microscopy With Tapered Tips for High Throughput
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Solution Overview
Problem
Current expansion microscopy (ExM) techniques are limited in throughput, allowing processing and imaging of few samples at a time, making them inaccessible for high-throughput applications.
Innovation Solution
A device and method for high-throughput Expansion Microscopy (hiExM) that enables parallel processing and imaging of samples in multi-well cell culture plates, using a device with tapered tips to deliver small volumes of solutions and facilitate gel expansion, compatible with conventional fluorescence microscopes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional expansion microscopy techniques are used, then high-resolution imaging of samples is achieved, but throughput remains low with only few samples processed at a time
Solution Approach 1:
The device segments the sample processing function into multiple independent posts (e.g., 96 posts for 96-well plates), allowing parallel processing of multiple samples simultaneously. Each post acts as an independent unit that can be inserted into individual wells, enabling high-throughput expansion microscopy while maintaining the simplicity of individual post operation.
Solution Approach 2:
The device is designed as a universal platform that can accommodate different well plate formats (6-well, 12-well, 24-well, 48-well, 96-well plates) using the same basic post structure. The posts can perform multiple functions including sample expansion, gel formation, and imaging preparation across various sample types and plate configurations.
2Productivity
If multiple samples are processed in parallel, then throughput increases, but solution delivery precision to each sample becomes more challenging
Solution Approach 1:
Each post is equipped with localized solution reservoirs and delivery mechanisms tailored to its specific well position. The tapered tip geometry varies locally to optimize solution delivery to the gel at the post tip, ensuring precise and consistent solution delivery to each sample while maintaining parallel processing capability across all posts.
3Loss of substance
If small volumes of solutions are delivered to each sample, then reagent consumption decreases, but delivery accuracy and consistency become more difficult to maintain
Solution Approach 1:
The device utilizes parameter changes in the post structure, particularly the tapered tip geometry, to control solution delivery. The tapering from base to tip creates capillary forces and surface tension effects that automatically regulate solution flow, ensuring consistent and accurate delivery of small volumes to each sample without requiring complex active control mechanisms.
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-resolution imaging of multiple samples simultaneously, improving throughput and accessibility for biological discovery and drug screening, with cost-effective and scalable solutions for diverse cell types.
Implementation Method 1
Expansion microscopy (ExM) involves the physical, isotropic expansion of biological samples
Implementation Method 2
allows for nanoscale resolution imaging using a diffraction limited microscope
Data Source
AI summary
Aspects of the present disclosure are directed to a device configured to be inserted into a well plate. The device may include a main body having a top side and a bottom side, and a plurality of posts extending downwardly from the bottom side of the main body, where the plurality of posts is sized to be inserted into a well plate. The device may further include a plurality of post passageways extending through the plurality of posts. The plurality of posts each have a terminus end opposite the main body, where the terminus ends of the plurality of posts further include a plurality of tapered tips. The present disclosure is also directed to methods of processing a plurality of samples in a well plate using the above-described device.