Implantable Enzyme Sensors With Internal NAD(P) Depot Control

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Solution Overview

Problem

Implantable analyte sensors face challenges with reduced sensitivity due to insufficient quantities of NAD or NADP, which can lead to reduced sensor performance, as these coenzymes are either not present in sufficient amounts or are too large to diffuse effectively to the enzyme site.

Innovation Solution

Incorporating an internal supply of NAD(P) within the sensor, overcoated with a permeable polymer to control diffusion and maintain sufficient NAD(P) concentration for extended monitoring periods.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If exogenous NAD or NADP is used to support enzyme activity in implantable sensors, then sensor operation can be maintained, but the molecules are too large to readily diffuse to the enzyme site, leading to reduced sensitivity

Engineering Contradiction:

Improvesensor operationVSAvoidsensor sensitivity

Core Design Contradiction:

ReliabilityVSMeasurement precision

Solution Approach 1:

The sensor is divided into distinct functional zones: an inner core containing the enzyme and a outer region containing the NAD(P) depot. This segmentation allows the large NAD(P) molecules to be stored in a dedicated reservoir rather than requiring diffusion through the entire sensor structure, resolving the contradiction between maintaining operation and preserving sensitivity.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The NAD(P) depot is nested within the sensor structure, with the depot containing the coenzyme molecules stored in an inner core region that is surrounded by a membrane. This nested arrangement allows direct access of NAD(P) to the enzyme while protecting the large molecules from needing to diffuse through external barriers.

Inventive Principle:

Principle #7Nested doll (Nesting)

2Duration of action of stationary object

If implantable sensors remain in tissue for extended periods, then continuous monitoring capability is achieved, but the sensors suffer from short life spans and reduced sensitivity

Engineering Contradiction:

Improvesensor lifespanVSAvoidsensor sensitivity

Core Design Contradiction:

Duration of action of stationary objectVSMeasurement precision

Solution Approach 1:

The NAD(P) depot is pre-loaded with sufficient coenzyme molecules before implantation to support enzyme activity throughout the entire intended lifespan of the sensor. This preliminary provisioning eliminates the need for ongoing external supply and ensures consistent sensitivity from implantation through the end of the sensor's operational life.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The sensor contains its own internal supply of NAD(P) molecules within the depot, making it self-sufficient for extended operation without requiring external replenishment. This self-service capability allows the sensor to maintain sensitivity and function independently for prolonged periods in the implantation site.

Inventive Principle:

Principle #25Self-service

3Quantity of substance

If sufficient quantities of exogenous NAD or NADP are provided, then enzyme activity can be supported, but the large molecular size prevents effective diffusion to the enzyme site

Engineering Contradiction:

ImproveNAD(P) availabilityVSAvoiddiffusion rate

Core Design Contradiction:

Quantity of substanceVSSpeed

Solution Approach 1:

The NAD(P) molecules are extracted from the external environment and placed into a dedicated internal depot within the sensor. This extraction eliminates the diffusion barrier by positioning the large molecules directly at the enzyme site rather than relying on their transport through tissue or sensor membranes.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

A membrane structure acts as an intermediary between the NAD(P) depot and the enzyme, controlling the release of coenzyme molecules. This intermediary mechanism ensures that sufficient quantities of NAD(P) are provided to the enzyme without requiring rapid diffusion through external barriers.

Inventive Principle:

Principle #24Intermediary (Mediator)

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 NAD(P)-dependent enzymes, enhancing the sensor's ability to accurately monitor analyte levels over time.

Implementation Method 1

a permeable polymer that overcoats the internal supply of NAD(P)... control diffusion and maintain sufficient NAD(P) concentration

Methodology Applied

Scientific EffectDiffusion: Diffusion

Data Source

PatentEP4262557B1NAD(p) depot for NAD(p)-dependent enzyme-based sensors

Publication Date: 2026.01.21 ABBOTT DIABETES CARE INC

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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.