Cryo-EM Sample Blotting with Optical Feedback Control
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Solution Overview
Problem
Current sample preparation methods for electron microscopy, particularly cryo-electron microscopy, face challenges in achieving reproducible and automated blotting of liquid films, leading to inconsistent sample quality and potential mechanical damage to sensitive biological samples due to manual and semi-automated processes.
Innovation Solution
A device equipped with an optical sensor device and a controller that detects changes in optical properties of the blotting medium, allowing for automatic and precise control of the blotting process, ensuring reliable and reproducible sample preparation by moving the blotting device away from the carrier upon detection of excess liquid absorption.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If manual or semi-automated blotting processes are used, then sample preparation can be performed, but reproducibility and consistency of sample quality deteriorate
Solution Approach 1:
The patent implements an optical sensor device that detects changes in optical properties of the blotting medium during the blotting process. This feedback mechanism allows the controller to automatically determine when excess liquid has been sufficiently removed and stop the blotting process at the optimal moment, ensuring consistent and reproducible sample preparation without requiring complex manual control systems.
Solution Approach 2:
The patent replaces manual mechanical blotting operations with an automated system that uses optical detection to control the process. The optical sensor device monitors the blotting medium's optical properties and provides signals to the controller, substituting human judgment and manual operation with objective optical measurement and automated control for improved reproducibility.
2Manufacturing precision
If extended optimization tests are performed to improve sample quality, then sample consistency improves, but time consumption increases
Solution Approach 1:
The patent enables the blotting device to self-regulate the blotting process through optical detection. The optical sensor automatically detects when the blotting medium has absorbed sufficient excess liquid and the optimal liquid film thickness is achieved, allowing the system to self-optimize without requiring external intervention or extensive manual testing, thereby reducing time consumption while maintaining sample consistency.
3Object-affected harmful factors
If manual blotting is used, then device complexity is low, but mechanical damage to sensitive biological samples increases
Solution Approach 1:
The optical sensor device provides real-time feedback to the controller about the blotting process status, allowing the system to apply and release pressure at precise moments. This feedback control prevents excessive or prolonged pressure application that could cause mechanical damage, while the automated system manages the complexity of pressure control more reliably than manual operation.
Solution Approach 2:
The patent replaces manual mechanical pressure application with an automated system controlled by optical detection. The controller receives signals from the optical sensor and automatically manages the blotting device's pressure application, substituting human manual control with automated mechanical control that reduces variability and minimizes mechanical damage to sensitive biological samples.
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
This solution enables the production of a large number of samples with consistent thickness and uniformity, reducing the need for lengthy optimization tests and minimizing mechanical damage, thus improving the reproducibility and reliability of the sample preparation process.
Implementation Method 1
detecting a change in optical properties of the blotting medium resulting from absorption of excess sample liquid in the blotting medium
Data Source
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AI summary
The invention relates to a device (100) for preparing samples for an electron microscope, in particular for a cryo-electron microscope, comprising a holding means (3) for holding a carrier (4), a movable blotting device (5) for draining excess sample liquid applied to the carrier by means of a substantially planar draining means (8), a control (17) configured to move the blotting device (5) towards the carrier (4), and a climate-controlled chamber (101) in which the holding means (3) and the blotting device (5) are arranged, wherein the device (100) further comprises an optical sensor device (12) with a light source (9) and a receiver (10), and the optical sensor device (12) is configuredThe invention relates to the illumination of the blotting medium (8) by means of the light source (9) and the detection of any change in the optical properties of the blotting medium (8) by means of the receiver (10) and the transmission of this information to the control unit (17), the control unit (17) being configured to move the blotting device (5) away from the support (4) when the optical properties of the blotting medium (8) change. The invention further relates to a method in which the device (100) is used.