Nozzle and Dispenser for Time-Resolved Electron Microscopy
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Solution Overview
Problem
Conventional scanning electron microscopy (SEM) and transmission electron microscopy (TEM) lack the capability to analyze biological and chemical structures at strict timescales, limiting the temporal resolution in time-resolved electron microscopy (EM) studies of protein structures and reaction mechanisms.
Innovation Solution
A nozzle and dispenser design that rapidly mixes substrates with a protein sample just before dispensing on an EM grid, utilizing a microfluidic device with a piezoelectric droplet generator and a 3D printed nozzle with specific channel diameters to facilitate rapid mixing and time-resolved EM studies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of time
If conventional microfluidic mixers are used to mix substrates with protein samples before dispensing, then mixing is achieved, but the mixing time is too long for time-resolved EM experiments
Solution Approach 1:
The nozzle performs preliminary mixing action just before dispensing, combining substrates and protein samples at the point of ejection rather than mixing them in advance in a separate chamber. This eliminates the time delay between mixing and dispensing, enabling time-resolved EM experiments to capture early reaction events.
Solution Approach 2:
The mixing function is extracted from the traditional pre-dispensing location and moved to the nozzle tip itself. The nozzle incorporates internal mixing channels that combine substrates and samples only milliseconds before ejection, separating the mixing operation from the dispensing operation in space and time.
2Measurement precision
If substrates and protein samples are mixed before entering the dispensing nozzle, then mixing is achieved, but the temporal resolution for capturing early reaction events is lost
Solution Approach 1:
The mixing and dispensing functions are merged into a single integrated nozzle assembly. The nozzle contains internal channels that bring substrate and sample streams together and mix them just before ejection, combining two operations that were previously separate into one unified device component.
Solution Approach 2:
The nozzle is segmented into distinct functional zones: separate inlet channels for substrate and sample, a mixing region where the streams combine, and an ejection aperture. This segmentation allows independent optimization of each function while maintaining compact integration.
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 time-resolved EM studies with improved temporal resolution, allowing for insights into protein structure and reaction mechanisms by ensuring rapid and efficient mixing of protein samples with substrates before EM analysis.
Implementation Method 1
The piezoelectric droplet generator is coupled to the first channel and to a sample source, the piezo-electric droplet generator configured to generate and provide droplets of the sample to the chamber
Data Source
AI summary
A device for time-resolved electron microscopy includes a nozzle and a piezoelectric droplet generator. The nozzle includes a chamber defining an inlet and an outlet, a first channel in fluid communication with the inlet of the chamber, and a second channel in fluid communication with the chamber. The piezoelectric droplet generator is coupled to the first channel and to a sample source. The piezo-electric droplet generator is configured to generate and provide droplets of the sample to the chamber. The second channel is configured to provide a substrate solution to the chamber, and the droplets of the sample and the substrate solution mix in the chamber and form a fluid stream when exiting the outlet for capture on an EM slide for study.