Implantable Brain Drug Delivery With Biomarker Feedback

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Solution Overview

Problem

Current methods for treating central nervous system (CNS) diseases such as glioma, traumatic brain injury, and Alzheimer's face challenges including the inaccessibility of the brain, the blood-brain barrier, and the lack of effective biomarkers for therapeutic efficacy, leading to slow drug development and ineffective clinical trials.

Innovation Solution

An implantable drug delivery and biomarker access device with a system of reservoirs and catheters that allows for long-term drug delivery and biomarker access within the brain parenchyma, utilizing one-way valves and microdialysis to collect and analyze extracellular biomarkers, enabling real-time feedback on drug efficacy and toxicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If current methods for treating CNS diseases are used, then treatment is provided, but the brain remains inaccessible and biomarker access is limited

Engineering Contradiction:
Improveaccess to brainVSAvoidtherapeutic efficacy assessment
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The device is segmented into multiple functional components: reservoirs for drug storage, catheters for delivery and sampling, one-way valves for directional control, and microdialysis membranes for biomarker access. This segmentation allows each component to perform its specific function efficiently while collectively providing comprehensive brain access and monitoring capability.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The implantable device acts as an intermediary between the external world and the brain parenchyma. It provides a controlled interface for drug delivery and biomarker sampling without requiring repeated surgical interventions, thereby improving both ease of operation and reliability of therapeutic assessment.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Duration of action of moving object

If long-term drug delivery to brain parenchyma is implemented, then therapeutic coverage is improved, but device complexity increases

Engineering Contradiction:
Improvedrug delivery durationVSAvoidimplantable device structure
Core Design Contradiction:
Duration of action of moving objectVSDevice complexity

Solution Approach 1:

The device merges multiple functions into a single implantable system: drug storage (reservoirs), delivery (catheters), directional control (one-way valves), and biomarker sampling (microdialysis). This consolidation enables long-term therapy while managing complexity through integrated design rather than separate components.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The implantable device is designed with multi-functionality to perform drug delivery, biomarker sampling, and therapeutic monitoring simultaneously. This universal approach allows long-term intervention with a single device rather than multiple separate systems, balancing duration of action with acceptable complexity.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Loss of information

If real-time biomarker monitoring is implemented, then therapeutic feedback is improved, but device complexity and measurement requirements increase

Engineering Contradiction:
Improvebiomarker feedbackVSAvoidbiomarker detection
Core Design Contradiction:
Loss of informationVSDifficulty of detecting and measuring

Solution Approach 1:

The device implements feedback by continuously sampling biomarkers from the brain parenchyma through microdialysis and returning samples to the reservoir. This closed-loop system provides real-time information on therapeutic response and toxicity, enabling dynamic adjustment of treatment while managing measurement complexity through automated sampling.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The microdialysis system operates autonomously to sample and concentrate biomarkers from the extracellular fluid. The device performs self-service by automatically drawing samples through pressure differentials and concentrating analytes without requiring external intervention, thereby improving feedback quality while reducing operational complexity.

Inventive Principle:
Principle #25Self-service

4Productivity

If multiple drugs are tested concurrently, then drug development efficiency is improved, but fluid flow control complexity increases

Engineering Contradiction:
Improvedrug testing throughputVSAvoidfluid flow control
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The device uses segmented reservoirs and separate catheter pathways for different drug formulations. Each reservoir-catheter pair can be independently controlled with one-way valves, allowing concurrent testing of multiple drugs while managing fluid flow complexity through modular, independent control sections rather than a single complex system.

Inventive Principle:
Principle #1Segmentation

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

This approach accelerates the discovery and translation of CNS therapies by providing patient-specific, real-time biological feedback, allowing for the concurrent testing of multiple drugs and the identification of biomarkers for therapeutic response and toxicity, thereby overcoming the limitations of existing methods.

Implementation Method 1

a first one-way valve disposed along a fluid connection between the first and second reservoirs, the first one-way valve oriented to allow fluid to flow from the first reservoir to the second reservoir and to prevent fluid from flowing from the second reservoir to the first reservoir

Methodology Applied
Scientific EffectOne-way valve mechanism: Valve

Implementation Method 2

a second one-way valve disposed along the return catheter, the second one-way valve oriented to allow fluid to flow from the return catheter to the first reservoir and to prevent fluid from flowing from the first reservoir to the return catheter

Methodology Applied
Scientific EffectOne-way valve mechanism: Valve

Implementation Method 3

a first reservoir configured to be implanted between a scalp and skull of a patient, the first reservoir being naturally biased to be in an expanded configuration; a second reservoir configured to be implanted between the scalp and the skull of the patient, the first reservoir being naturally biased to be in an unexpanded configuration

Methodology Applied
Scientific EffectElastic recovery: Elasticity

Data Source

PatentEP3887685B1Drug delivery and biomarker access devices
Publication Date: 2023.08.16 MAYO FOUNDATION FOR MEDICAL EDUCATION & RESEARCH
  • EP3887685B1 patent drawingFigure 1
  • EP3887685B1 patent drawingFigure 2~3
  • EP3887685B1 patent drawingFigure 4

AI summary

This document describes devices for in vivo drug testing in the brain. This document also describes implantable devices for long-term drug delivery to the brain parenchyma, and for access to biomarkers from the parenchyma.