Internal NAD(P) Depot for Sustained Enzyme Sensor Sensitivity
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Solution Overview
Problem
Implantable analyte sensors face challenges with reduced sensitivity due to insufficient quantities of NAD or NADP, which are essential for enzyme activity, and the large molecular size of these coenzymes hinders their diffusion to the sensing chemistry layer.
Innovation Solution
Incorporating an internal supply of NAD(P) within the sensor, coated with a permeable polymer to control diffusion and maintain sufficient NAD(P) concentration for extended analyte monitoring.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If exogenous NAD or NADP is used to support enzyme activity in implantable sensors, then sensor sensitivity can be maintained, but the large molecular size of these coenzymes hinders their diffusion to the sensing chemistry layer, reducing effectiveness
Solution Approach 1:
The sensor is divided into distinct functional layers: a sensing chemistry layer containing the enzyme and a separate NAD(P) depot layer. This segmentation allows the NAD(P) to be stored in high concentration in the depot and diffuse controllably to the sensing layer, overcoming the diffusion limitation while maintaining enzyme activity and sensor sensitivity.
Solution Approach 2:
NAD(P) is pre-loaded into the sensor device at high concentration in the depot before implantation. This preliminary action ensures that sufficient NAD(P) is available at the sensing chemistry layer from the start, eliminating the need for continuous exogenous supply and ensuring immediate enzyme activity upon implantation.
2Duration of action of moving object
If implantable sensors are designed for extended monitoring periods, then continuous analyte data can be collected, but the sensors face reduced sensitivity and short life spans due to insufficient NAD or NADP availability
Solution Approach 1:
The sensor is pre-loaded with a reservoir of NAD(P) at high concentration before implantation. This preliminary action ensures that the enzyme has sufficient coenzyme available throughout the extended operational period, maintaining sensor sensitivity and preventing the decline that would otherwise occur over time.
Solution Approach 2:
The NAD(P) depot is nested within the sensor device structure, with the sensing chemistry layer positioned to receive NAD(P) from the internal depot. This nested configuration allows the sensor to be self-sufficient, containing its own NAD(P) supply internally, thereby extending operational lifespan while maintaining sensitivity without requiring external NAD(P) supply.
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 internal NAD(P) depot ensures sustained sensor sensitivity by providing a consistent supply of NAD(P) to the NAD(P)-dependent enzymes, enhancing the sensor's ability to accurately monitor analyte levels over an extended period.
Implementation Method 1
a permeable polymer that overcoats the internal supply of NAD(P)... providing a consistent supply of NAD(P) to the NAD(P)-dependent enzymes
Data Source
Figure 1A
Figure 1B
Figure 2A
AI summary
The present disclosure provides analyte sensors including one or more NAD(P)-dependent enzymes and an internal supply of NAD(P) for the detection of an analyte. The present disclosure further provides methods of using such analyte sensors for detecting one or more analytes present in a biological sample of a subject, and methods of manufacturing said analyte sensors.