Cryo-EM Sample Grid With Dual GUIDs for Post-Vitrification Tracking
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Solution Overview
Problem
Current sample grids for cryogenic electron microscopy (cryo-EM) lack a reliable method for global identification after the vitrification process, leading to tracking issues and misidentifications due to thermal interference and location-based record-keeping systems becoming complex.
Innovation Solution
Cryo compatible sample grids with multi-modal GUIDs that include optical and electron-readable identifiers, allowing identification before and after vitrification, using a first identifier readable with an optical detector and a second identifier readable with an electron microscope, even when filled with ice.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current identification techniques are used on sample grids, then identification is possible before vitrification, but the techniques become unreliable or inoperative after vitrification and introduce excess thermal mass that interferes with the vitrification process
Solution Approach 1:
The identification system is segmented into two separate identifiers: a first identifier (optical barcode/QR code) on the outer support structure for pre-vitrification identification, and a second identifier (pattern of holes) within the sample region for post-vitrification identification. This segmentation allows each identifier to be optimized for its specific function without interfering with the vitrification process
Solution Approach 2:
The second identifier uses a pattern of holes that serve as an intermediary structure - these holes can be filled with vitrified sample solution to create a readable pattern after vitrification, without requiring additional thermal mass during the process. The holes act as a mediator between the physical grid structure and the identification function
2Ease of operation
If location-based record-keeping systems are used to track sample grids, then identification is possible through physical location tracking, but the systems rapidly become complex and prone to misidentifications when managing large numbers of grids
Solution Approach 1:
The sample grid itself carries its own unique identification codes (both optical and electron-readable) directly on its structure. This self-service approach eliminates the need for complex external tracking systems that map physical locations to sample identities. The grid identifies itself through the identifiers embedded in its structure, making the tracking system as simple as reading the code
Solution Approach 2:
The identification information is copied onto the sample grid structure itself in multiple formats (optical barcode/QR code and electron-readable hole pattern). This creates a permanent, portable copy of the identification data that travels with the grid regardless of location, eliminating the need for complex location-based record-keeping
3Duration of action of stationary object
If sample grids are vitrified for long periods and stored in large quantities, then cryo-EM workflows can be maintained, but tracking and identification become difficult due to grid swaps and loss of association between grids and samples
Solution Approach 1:
The identification system utilizes parameter changes during vitrification - the second identifier is designed so that the holes can be filled with vitrified sample solution, changing the physical state of the identifier region from air-filled to ice-filled. This parameter change allows the identifier to remain functional and readable after vitrification, maintaining identification capability throughout long-term storage
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 accurate and efficient tracking and identification of sample grids throughout cryo-EM workflows, reducing misidentifications and simplifying the management of large numbers of grids.
Implementation Method 1
The first identifier is readable with an optical detector
Implementation Method 2
using an electron microscope to generate an electron microscope image of a cryo compatible sample grid that has been subjected to a vitrification process
Implementation Method 3
the sample grid/solution(s) thereon are cooled so rapidly that water molecules in the aqueous solution do not have time to crystallize, forming an amorphous solid
Data Source
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AI summary
Cryo compatible sample grids having multi-modal cryo-EM compatible GUIDs, according to the present disclosure include an outer support structure that defines a region of the grid for holding one or more samples, and a plurality of inner support structures that define a plurality of apertures that are each configured to hold a sample. Cryo compatible sample grids further include a first identifier located on the outer support structure, and a second identifier located within the region of the grid for holding the one or more samples. The first identifier is readable with an optical detector, while the second identifier is readable with an electron detector (e.g., within an electron microscope). Specifically, the second identifier is readable with an electron detector when one or more teeth and/or holes that comprise the second identifier are filled with ice from a vitrification process.