Nanobody Functionalized OECT Biosensors for Rapid Pathogen Detection
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Solution Overview
Problem
Current diagnostic methods for detecting pathogens like HIV, Ebola, and SARS-CoV-2 are either labor-intensive and require specialized equipment or lack sensitivity and quantification, hindering rapid and accurate point-of-care diagnostics.
Innovation Solution
Development of organic electrochemical transistors (OECTs) with a biorecognition layer comprising self-assembled monolayers (SAMs) and nanobodies for specific antigen detection, enabling stable and sensitive biosensing without the need for labels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If PCR or RT-PCR methods are used for pathogen detection, then detection accuracy and sensitivity are improved, but device complexity and operational difficulty increase due to requiring specialized equipment and specialist labor
Solution Approach 1:
The patent replaces complex mechanical and chemical PCR amplification systems with an electrochemical detection system using OECTs. The OECT transduces binding events between nanobodies and viral antigens directly into electrical signals, eliminating the need for thermal cycling equipment, reagents, and specialized laboratory infrastructure while maintaining high detection sensitivity.
Solution Approach 2:
The patent introduces nanobodies as intermediary recognition elements that specifically bind to viral antigens (such as SARS-CoV-2 spike protein). These nanobodies are integrated into the OECT gate structure, serving as a bridge between the target analyte and the electrical detection system, enabling specific and sensitive detection without complex amplification procedures.
2Ease of operation
If lateral-flow ELISA rapid tests are used for on-spot detection, then operational ease and speed are improved, but detection sensitivity deteriorates to approximately 1 million particles per mL
Solution Approach 1:
The patent changes the detection parameter from optical signal measurement in lateral-flow assays to electrical signal measurement using OECTs. The OECT's high transconductance amplifies the electrical signal from nanobody-antigen binding events, enabling detection at femtomolar concentrations (1.8 x 10^-17 M), which is several orders of magnitude more sensitive than lateral-flow tests while maintaining operational simplicity.
Solution Approach 2:
The patent employs a dynamic two-step functionalization process where nanobodies are first immobilized on the OECT gate via a self-assembled monolayer, creating an active biosensing surface. This dynamic preparation enables the device to transition from a passive electronic component to an active biosensor capable of real-time electrical detection with high sensitivity.
3Loss of time
If lateral-flow ELISA rapid tests are used for pathogen detection, then detection speed is improved with results in about 15 minutes, but the ability to provide quantitative information on pathogen load deteriorates
Solution Approach 1:
The patent implements a quantitative feedback mechanism where the electrical current output of the OECT is directly proportional to the concentration of bound viral antigens. By measuring the change in drain current or threshold voltage shift, the system provides real-time quantitative information on pathogen load, enabling not only detection but also monitoring of viral concentration dynamics during the 15-minute assay period.
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 OECT-based biosensors provide high sensitivity (1.8 x 10^-17 M for SARS-CoV-2 Spike protein), selectivity, and rapid detection (15 minutes) with a low limit of detection, suitable for point-of-care use and compatible with smartphone-based readouts.
Implementation Method 1
The biorecognition layer comprises self-assembled monolayers (SAMs) and nanobodies for specific antigen detection
Implementation Method 2
The biorecognition layer comprises self-assembled monolayers (SAMs) and nanobodies
Implementation Method 3
Organic electrochemical transistors (OECTs) have attracted attention as a promising alternative biosensing technology
Data Source
Figure 1A~1C
Figure 1D
Figure 2A~2B
AI summary
Organic electrochemical transistor (OECT)-based immunosensors, methods of making and methods of use thereof are provided herein. The immunosensor includes an OECT and a biorecognition layer. The biorecognition layer is preferably integrated on the gate electrode of the OECT. The biorecognition layer includes a self-assembled monolayer (SAM) of organic molecules, a linker, and a biorecognition element preferably, a nanobody. In a preferred embodiment, the organic molecules forming the SAM include thiols. The disclosed methods can be used to make OECT devices containing a nanobody whose binding partner is any analyte of interest, such as SARS-2 RBD, S1 or the virus itself.