STEM Stitching for Polymer Sequencing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Conventional transmission electron microscopy for polymer sequencing faces challenges such as low signal-to-noise ratio, poor focusing, and low throughput, making it inefficient for sequencing long polymers like the human genome.
Innovation Solution
A scanning transmission electron microscope (STEM) is designed with an electron beam source, beam optics, a stage, and detectors to generate and scan an electron beam across a specimen, allowing for the creation of stitched-together images that enable accurate sequencing by identifying labels on polymer strands.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional transmission electron microscopy is used for polymer sequencing, then the imaging process can be performed, but the signal-to-noise ratio is low making label identification difficult
Solution Approach 1:
The imaging process is divided into multiple scanning passes over different regions of interest along the polymer strand. Each pass generates a sub-image that is later stitched with other sub-images, allowing the system to concentrate scanning resources on areas containing labels rather than uniformly scanning the entire strand, thereby improving signal-to-noise ratio for label detection.
Solution Approach 2:
The beam scanner and stage are dynamically coordinated to perform selective scanning. The system adjusts scanning parameters and positions based on real-time feedback and pre-acquired information about label locations, enabling adaptive optimization of the signal-to-noise ratio for detecting structural units with labels.
2Manufacturing precision
If conventional transmission electron microscopy is used, then imaging can be performed, but the images are not optimally focused at every portion of the polymer strand
Solution Approach 1:
The polymer strand is divided into multiple scanning areas along its length. The beam scanner and stage are controlled to systematically scan through each scanning area, ensuring that each segment receives optimized focusing conditions. This segmented approach allows the system to maintain optimal focus across the entire extended polymer strand.
Solution Approach 2:
The system uses feedback mechanisms to monitor and adjust focusing conditions during scanning. By continuously evaluating image quality and making real-time adjustments to beam parameters and stage positioning, the system ensures optimal focus is maintained across all portions of the polymer strand being imaged.
3Productivity
If conventional transmission electron microscopy is used for sequencing, then the process can be completed, but it takes an undesirably long time especially for long polymers
Solution Approach 1:
The sequencing task is segmented into multiple parallel scanning operations across different regions of the polymer strand. While one region is being scanned, the system can simultaneously prepare or process data from other regions, enabling parallel processing that dramatically reduces total sequencing time for long polymers like the human genome.
Solution Approach 2:
The system performs preliminary scanning to identify locations of structural units with labels before conducting detailed analysis. This preliminary action allows the system to pre-plan the scanning path and prioritize regions containing labels, eliminating unnecessary scanning of empty regions and significantly reducing overall sequencing time.
4Area of stationary object
If the electron beam is scanned across the entire specimen at once, then complete coverage is achieved, but the throughput is reduced due to the large area requiring scanning
Solution Approach 1:
The large scanning area is divided into multiple smaller scanning areas or regions of interest. The beam scanner systematically moves through each sub-region, generating sub-images that are later stitched together. This segmentation allows the system to maintain high throughput by processing smaller areas efficiently while still achieving complete coverage of the entire specimen.
Solution Approach 2:
The system performs scanning with a focus on partial coverage of specific regions containing labels rather than uniformly scanning the entire available area. By concentrating scanning resources on regions of interest where labels are located, the system achieves sufficient coverage for sequencing purposes while dramatically improving throughput by avoiding unnecessary scanning of empty regions.
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
The STEM improves the signal-to-noise ratio, ensures focused imaging across the entire polymer strand, and significantly increases sequencing throughput, making it practical for sequencing long polymers like the human genome.
Implementation Method 1
an electron beam source to generate an electron beam
Implementation Method 2
beam optics to converge the electron beam
Implementation Method 3
a beam scanner to scan the electron beam across the specimen
Implementation Method 4
a detector to detect electrons transmitted through the specimen to generate an image
Data Source
AI summary
A scanning transmission electron microscope for imaging a specimen includes an electron beam source to generate an electron beam. Beam optics are provided to converge the electron beam. A stage is provided to hold a specimen in the path of the electron beam. A beam scanner scans the electron beam across the specimen. A controller may define one or more scanning areas corresponding to locations of the specimen, and control one or more of the beam scanner and stage to selectively scan the electron beam in the scanning areas. A detector is provided to detect electrons transmitted through the specimen to generate an image. The controller may generate a sub-image for each of the scanning areas, and stitch together the sub-images for the scanning areas to generate a stitched-together image. The controller may also analyze the stitched-together image to determine information regarding the specimen.