Nanogap Electrode Biomolecule Sequencing with Reference Substance
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Solution Overview
Problem
Current methods for identifying monomers in biomolecules using nano current measurements with nanogap electrode pairs are limited by variability in measurement results and require additional steps like separation and refinement, especially when dealing with unknown molecules, and lack standardization for samples with varying molecular species.
Innovation Solution
A method utilizing standardized nano current measurements with nanogap electrode pairs that includes a reference substance to stabilize signals, allowing for the identification of monomers without separation or refinement steps, by using a reference substance with known signal characteristics to normalize measurements across different conditions and distances between electrodes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional standardization methods are applied to nano current measurement using nanogap electrode pairs, then measurement results can be standardized, but samples and conditions are limited and additional separation or refinement steps are required
Solution Approach 1:
The patent introduces a reference substance as an intermediary that mediates between the nanogap electrode measurement system and the sample molecules. This reference substance, with known molecular weight and structure, serves as a calibration standard that enables direct measurement without separation steps. The reference substance translates the complex measurement conditions into standardized, comparable data across different samples and instruments.
2Measurement precision
If measurement time is extended to sufficiently measure the internal reference substance, then standardization can be achieved, but measurement efficiency decreases
Solution Approach 1:
The reference substance is pre-selected and pre-characterized with known molecular weight, structure, and expected signal characteristics. This preliminary preparation allows the measurement system to be pre-calibrated, eliminating the need for extended measurement times during actual sample analysis. The system is prepared in advance to quickly process samples while maintaining standardization accuracy.
3Measurement precision
If conventional methods are used to detect specific chemical species, then specific monomers can be identified, but the method cannot be applied to biomolecule sequencing with various molecular species
Solution Approach 1:
The patent employs a universal measurement approach based on tunneling current that can detect all types of molecules regardless of their chemical structure. Unlike conventional methods that require specific chemical modifications for different monomer types, this system uses a single measurement principle (tunneling current through nanogap electrodes) that universally applies to proteins, nucleic acids, and other biomolecules, enabling both specific identification and broad versatility.
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 precise and efficient identification of monomers in biomolecules by stabilizing signals and standardizing measurements, allowing for accurate sequencing of biomolecules without the need for additional processing steps, even with unknown molecules, and optimizing signal detection to prevent noise interference.
Implementation Method 1
measuring signals corresponding to nano currents (e.g., tunneling currents) that flow when a reference substance and at least one or more kinds of monomer to be identified
Data Source
AI summary
Devices, systems and methods for sequencing protein samples are provided. In some examples, currents generated when a monomer passes through between electrodes of a nanogap electrode pair are measured for each of several different distances, so that monomers are identified when compared to a reference physical quantity of a known monomer, which may be obtained from a current measured with a similar inter-electrode distance(s) at which each of plural kinds of monomers are identifiable and ordered with predetermined accuracy and based on a detected physical quantity obtained from a tunneling current, which may be further normalized by the use of one or more reference substances.