Microfabricated Silicon CED Device for Brain Tissue Delivery
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Solution Overview
Problem
Convection-enhanced drug delivery (CED) techniques face challenges in controlling drug distribution due to tissue heterogeneity and backflow issues with conventional needles, particularly in delivering nanoparticles and achieving effective penetration in brain tissue, where the extracellular matrix restricts particle size and distribution.
Innovation Solution
A microfabricated silicon-based CED device with parylene channels and integrated sensors for precise drug delivery, capable of delivering drugs under positive pressure with reduced backflow and occlusion, and enzymatic digestion to enhance nanoparticle penetration by modifying the extracellular matrix, allowing for simultaneous or sequential delivery of multiple agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If conventional needles are used for CED, then drug infusion can be achieved, but backflow occurs and control over drug delivery is reduced
Solution Approach 1:
The delivery device is segmented into multiple components: a cannula for insertion, a receiver for fluid collection, and a pump for controlled delivery. This segmentation allows the system to address backflow by collecting and recycling fluid through the receiver while maintaining controlled delivery through the pump, thereby improving control over drug delivery.
Solution Approach 2:
The system incorporates a pump that can detect and respond to flow conditions, providing feedback control to prevent backflow. The pump monitors the infusion process and adjusts delivery parameters accordingly, ensuring precise control over drug delivery while eliminating the harmful backflow effect.
2Speed
If high flow rates are used to increase penetration distance, then convection rate increases, but backflow of infused solutions occurs
Solution Approach 1:
The system extracts and separates the backflow component from the forward delivery stream. By using a receiver to collect fluid and a pump to manage flow, the system can maintain high convection rates for penetration while extracting the backflow portion that would otherwise compromise delivery control.
Solution Approach 2:
The pump acts as an intermediary between the high flow rate requirement for penetration and the backflow prevention need. It mediates the flow dynamics, allowing high convection rates to achieve penetration distance while preventing backflow through controlled pressure regulation and flow management.
3Area of stationary object
If large tumor size is present, then treatment coverage requirement increases, but delivery into dense tissue becomes difficult
Solution Approach 1:
The system uses dynamic pump control to adapt delivery parameters to tissue density variations. The pump can adjust flow rate, pressure, and infusion characteristics in real-time based on tissue resistance, enabling effective delivery into dense tumor tissue while maintaining coverage of large tumor volumes.
Solution Approach 2:
The system changes delivery parameters such as flow rate, pressure, and infusion speed to optimize penetration into dense tissue. By dynamically adjusting these parameters, the system can overcome the barrier of dense tissue while maintaining sufficient treatment coverage for large tumor sizes.
4Power
If needle tip pressure is high, then infusion can be initiated, but needle tip occlusion is indicated
Solution Approach 1:
The system performs preliminary actions to prevent needle tip occlusion before infusion begins. By using a receiver to collect fluid and a pump to control pressure from the start, the system prevents the high pressure buildup that would indicate occlusion, ensuring reliable infusion initiation and continuous operation.
Solution Approach 2:
The system uses its own pump and receiver components to self-regulate pressure and prevent occlusion. The pump actively manages pressure to maintain patency, and the receiver collects fluid that might otherwise contribute to occlusion, allowing the system to serve itself in preventing needle tip blockage.
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 microfabricated device achieves higher drug delivery rates with reduced backflow and improved spatial resolution, enabling deeper tissue penetration and enhanced nanoparticle distribution, overcoming limitations of conventional CED methods.
Implementation Method 1
Convection-enhanced drug delivery (CED) uses direct infusion of a drug-containing liquid into tissue so that transport is dominated by convection.
Implementation Method 2
When diffusion is the dominant transport mechanism, the concentration of the drug decays exponentially with distance from the implant.
Implementation Method 3
enzymatic digestion to enhance nanoparticle penetration by modifying the extracellular matrix
Data Source
AI summary
An embodiment of the invention is directed to a microfabricated, silicon-based, Convection Enhanced Delivery (CED) device. The device comprises a silicon shank portion, at least one individual parylene channel disposed along at least a part of an entire length of the shank, wherein the channel has one or more dimensioned fluid exit ports disposed at one or more respective locations of the channel and a fluid (drug) input opening. The fluid input opening may be configured or adapted to be connected to a fluid reservoir and/or a pump and/or a meter and/or a valve or other suitable control device(s) or apparatus that supplies and/or delivers fluid (eg, a drug) to the microfabricated device. The device may have multiple channels disposed side by side or in different surfaces of the device.