Engineered Glucose Binding Protein Sensor
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Solution Overview
Problem
Current continuous glucose monitoring (CGM) sensors face challenges such as invasive blood extraction, pain, and limited compliance due to the need for chemical reactions and enzymatic conversion, which result in inaccurate low glucose readings, short sensor life, and interference from electrochemical interferents.
Innovation Solution
A novel electrochemical analyte sensor using an engineered glucose binding protein that changes conformation in response to glucose binding, exposing or occluding a redox mediator to generate a measurable signal, eliminating the need for enzymatic conversion and reducing interference, with a simpler design and longer sensor life.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If Clark-type amperometric detection is used to measure glucose, then continuous glucose monitoring is enabled, but invasive blood extraction and pain are required
Solution Approach 1:
The patent replaces the mechanical blood extraction system with a non-invasive interstitial fluid sampling system. The sensor measures glucose through electrochemical detection of glucose oxidase activity in interstitial fluid, eliminating the need for lancets and pinpricks while maintaining continuous monitoring capability.
Solution Approach 2:
The patent uses an artificial mediator that shuttles electrons between glucose oxidase and the electrode, enabling glucose detection through interstitial fluid rather than requiring direct blood sampling. This intermediary approach allows continuous monitoring through less invasive means.
2Measurement precision
If electrochemical oxidation of hydrogen peroxide is used for glucose measurement, then glucose concentration can be detected, but interference from electrochemical interferents occurs
Solution Approach 1:
The patent extracts the harmful electrochemical oxidation step that generates interference. Instead of oxidizing hydrogen peroxide at the electrode, the system uses an artificial mediator to transfer electrons from glucose oxidase to the electrode at a lower potential, removing the source of electrochemical interferent interference.
Solution Approach 2:
The patent changes the electrochemical parameters by using an artificial mediator with a lower oxidation potential than hydrogen peroxide. This parameter change shifts the operating potential away from the range where electrochemical interferents are oxidized, thereby reducing interference.
3Measurement precision
If enzymatic conversion by glucose oxidase is used, then glucose can be detected, but sensor life is limited due to enzyme degradation
Solution Approach 1:
The patent introduces an artificial mediator as an intermediary between glucose oxidase and the electrode. This mediator is more stable than the natural electron transfer chain, protecting the enzyme from degradation and extending sensor life while maintaining glucose detection precision.
Solution Approach 2:
The patent provides protective measures in advance by using a stable artificial mediator system that shields glucose oxidase from harsh electrochemical conditions. This cushioning approach prevents enzyme degradation before it can occur, extending the operational life of the sensor.
4Measurement precision
If indirect measurement of enzymatic products is used, then glucose can be detected, but the system complexity increases
Solution Approach 1:
The patent merges the enzyme layer and electron transfer mediator into a single integrated sensing interface. The artificial mediator is embedded within the enzyme layer, combining the enzymatic conversion and electron transfer functions into one simplified structure, reducing overall system complexity.
Solution Approach 2:
The artificial mediator serves multiple functions simultaneously: it accepts electrons from glucose oxidase, transports them to the electrode, and maintains enzyme stability. This multi-functionality reduces the number of separate components needed, simplifying the overall system.
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 sensor provides accurate, long-lasting glucose monitoring with improved signal-to-noise ratio and reduced interference, allowing for continuous, non-invasive glucose tracking with enhanced compliance and reduced complexity in manufacturing and calibration.
Implementation Method 1
A first binding protein configured to have a first conformation and a second conformation, where electrons are transferred to the electrode surface when the first binding protein is in the first conformation
Data Source
AI summary
Aspects of the present disclosure provide devices and methods capable of optimizing in vivo electrochemical measurement of a molecule of interest, for example glucose. Such aspects may include an engineered binding protein, for example an engineered glucose binding protein. The engineered binding protein may change conformation in response to binding or unbinding to a ligand and/or analyte, for example glucose. Such conformational changes may either expose or occlude a redox molecule attached to the binding protein. When exposed, the redox molecule may generate a redox signal dependent upon the binding protein's conformational state. The redox signal may be measurable, for example by cyclic voltammetry. The protein may be incorporated into a sensor that can be used as an implantable continuous glucose monitoring device.