Functionalized Nanopipette Biosensor for Label-Free Biomolecule Detection
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Solution Overview
Problem
Current biomolecule detection methods require multiple copies of analytes and involve complex labeling and pretreatment processes, limiting their sensitivity and efficiency in detecting specific molecules such as cancer biomarkers and pathogens.
Innovation Solution
A nanopipette device with a nanoscale opening and chemically attached peptide-binding molecules that can detect analytes by blocking ionic current flow, allowing for specific detection of molecules without labeling or pretreatment, using a voltage clamp circuit to measure current changes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional biomolecule detection methods are used, then multiple copies of analytes can be detected, but the detection sensitivity and efficiency are limited due to complex labeling and pretreatment processes
Solution Approach 1:
The invention extracts and eliminates the complex labeling and pretreatment steps from the detection process by using a nanopipette-based system that directly detects analytes through ionic current blockage, achieving single-molecule sensitivity without requiring multiple copies or complex sample preparation
Solution Approach 2:
The invention replaces the mechanical and chemical complexity of labeling procedures with an electrical measurement system where analytes are detected through their physical blockage of ionic current flow through the nanopipette, simplifying the detection process while maintaining high sensitivity
2Ease of operation
If nanopipette with chemically attached peptide-binding molecules is used, then individual molecules can be detected without labeling, but the device structure becomes more complex
Solution Approach 1:
The nanopipette is pre-functionalized with chemically attached peptide-binding molecules during manufacturing, allowing the device to be used directly for detection without requiring labeling or complex sample preparation steps during operation
Solution Approach 2:
The functionalized nanopipette performs self-detection by utilizing the natural binding interaction between the attached peptide-binding molecules and target analytes, where the binding event itself generates the detectable ionic current blockage signal without requiring external labeling reagents
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 sensitive and real-time detection of individual molecules, including cancer biomarkers and pathogens, with potential for multiplexed analysis and low detection limits, improving diagnostic capabilities and reducing costs compared to existing techniques.
Implementation Method 1
The internal volume will contain electrolyte, and the sample will contain electrolyte. The purpose of the electrolyte is to provide a source of ions for ionic current flow
Implementation Method 2
Blocking by specific binding of an analyte causes a reduction of ionic current flow through the electrolyte solution
Data Source
AI summary
Disclosed are methods and devices for biomolecular detection, comprising a nanopipette, exemplified as a hollow inert, non-biological structure with a conical tip opening of nanoscale dimensions, suitable for holding an electrolyte solution which may contain an analyte such as a protein biomolecule to be detected as it is passed through the tip opening. Biomolecules are detected by specific reaction with peptide ligands chemically immobilized in the vicinity of the tip. Analytes which bind to the ligands cause a detectible change in ionic current. A sensitive detection circuit, using a feedback amplifier circuit, and alternating voltages is further disclosed. Detection of IL-10 at a concentration of 4 ng/ml is also disclosed, as is detection of VEGF.