Aptamer-Based Protein Sequencing Platform for High-Throughput Analysis
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Solution Overview
Problem
Current methods for protein sequencing are not cost-effective or efficient for large-scale, high-throughput sequencing across the entire dynamic range of protein expression, and they struggle to sequence untargeted lowly expressed proteins, including antibodies and proteins from other organisms present in a host's bloodstream.
Innovation Solution
A protein sequencing platform utilizing aptamers that bind specifically to N-terminal amino acids, generated using novel methods like RCHT-SELEX and NTAA-SELEX, which allow for the recognition and identification of amino acids through DNA barcoding and visual signals, enabling simultaneous selection and screening of multiple targets.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If current protein sequencing methods are used, then sequencing can be performed, but the process is not cost-effective and inefficient for large-scale, high-throughput sequencing
Solution Approach 1:
The patent segments the protein sequencing process into distinct functional modules: aptamer binding to specific amino acid residues, barcode attachment to captured aptamers, and sequential processing of multiple protein targets. This modular segmentation enables parallel processing and optimization of each step, significantly improving throughput while reducing overall costs through standardized protocols.
Solution Approach 2:
The patent introduces aptamers as intermediary molecules that bind specifically to target amino acid residues, serving as mediators between the protein sample and the detection system. These aptamers are coupled with barcodes that enable identification, creating an efficient intermediary layer that amplifies signal and enables high-throughput processing without requiring direct, complex protein-protein interactions.
2Adaptability or versatility
If current sequencing methods are used, then some proteins can be sequenced, but untargeted lowly expressed proteins including antibodies cannot be effectively sequenced
Solution Approach 1:
The patent creates a universal sequencing platform where a single aptamer library can be used to detect and sequence diverse protein targets including lowly expressed proteins and antibodies. The system uses universal barcode structures and standardized processing protocols that work across different protein types, enabling the same platform to adaptively sequence any protein in the sample without requiring target-specific optimization.
Solution Approach 2:
The patent performs preliminary enrichment and capture of target proteins using aptamer binding before detection. By pre-concentrating lowly expressed proteins through specific aptamer-antigen interactions and attaching barcodes in advance, the system amplifies the signal from rare proteins, making them detectable alongside highly abundant proteins in the same sample.
3Measurement precision
If aptamers are used for specific amino acid recognition, then identification accuracy improves, but the complexity of generating and managing aptamer libraries increases
Solution Approach 1:
The patent uses barcode sequences as informational copies that represent the identity of bound aptamers. Instead of directly analyzing complex aptamer structures, the system attaches simplified barcode copies to captured aptamers, which can then be readily sequenced and decoded to identify the original amino acid targets. This copying approach maintains high identification accuracy while dramatically simplifying the management and analysis of aptamer library data.
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 approach enables efficient and cost-effective large-scale protein sequencing, including lowly expressed proteins, by generating specific aptamers that can identify and convert amino acids into DNA sequences, facilitating deeper understanding of protein presence and modifications, and aiding in therapeutic efficacy monitoring.
Implementation Method 1
aptamers that bind specifically to N-terminal amino acids
Data Source
AI summary
This disclosure describes methods and compositions for protein and peptide sequencing.