Fabrication and In Vivo Testing of a Sub-mm Duckbill Valve for Hydrocephalus Treatment

Academic Background

Hydrocephalus is a complex pathological condition characterized by the accumulation of cerebrospinal fluid (CSF) in the cranium due to an imbalance between CSF production and absorption. This accumulation leads to increased intracranial pressure (ICP), which can cause damage to the brain. The standard treatment for hydrocephalus involves the implantation of a shunt to divert excess CSF to the peritoneal cavity. However, shunts have a high failure rate over time, often requiring multiple surgeries for repair or replacement. Common causes of shunt failure include obstruction, infection, over-drainage, or under-drainage. Therefore, developing a more reliable and effective alternative is a critical focus of current research.

This study proposes a miniaturized duckbill valve designed to mimic the natural one-way valve function of the arachnoid granulations (AGs), which are key structures for CSF drainage from the subarachnoid space (SAS) to the superior sagittal sinus (SSS). By designing a miniaturized valve that can be implanted within the cranium, the research team aims to reduce complications associated with traditional shunt systems and provide a more effective CSF drainage solution.

Source of the Paper

The paper was co-authored by Yuna Jung, Daniel Gulick, and Jennifer Blain Christen, all from the Department of Electrical, Computer, and Energy Engineering at Arizona State University, USA. The paper was published in 2024 in the journal Microsystems & Nanoengineering, titled “Fabrication and in vivo testing of a sub-mm duckbill valve for hydrocephalus treatment.”

Research Process and Results

1. Fabrication of the Duckbill Valve

The research team used polydimethylsiloxane (PDMS) as the material to design and fabricate a miniaturized duckbill valve. The fabrication process included the following steps:

• Photolithography: A layer of photoresist (PR) was spin-coated onto a silicon wafer, followed by spin-coating PDMS prepolymer, which was then cured. Oxygen plasma treatment was applied to enhance the adhesion between PDMS and the subsequent PR layer.
• Photolithographic Patterning: A second layer of PR was spin-coated onto the PDMS surface, and the fluid channel pattern was formed through UV exposure and development.
• PDMS Layering: Another layer of PDMS was spin-coated onto the patterned PDMS surface, cured, and then peeled off from the silicon wafer to form a double-layer PDMS structure.
• Fluid Channel Formation: The PR sandwiched between the two PDMS layers was dissolved using acetone to form the fluid channel.
• Silicone Tube Insertion: A silicone tube was inserted into the gap between the PDMS layers and sealed with silicone adhesive.

2. Benchtop Testing

The research team designed a benchtop testing system to evaluate the performance of the duckbill valve. The testing system included a programmable syringe pump, a pressure sensor, and a flow sensor. Through this system, the researchers measured the valve’s cracking pressure and outflow resistance. The experimental results showed that the valve exhibited excellent unidirectional flow with negligible reverse leakage. By adjusting the width of the fluid channel (w) and the bill length (l), the researchers were able to control the valve’s cracking pressure within the low-pressure range of conventional shunt valves (2.22 ± 0.07 mmHg).

3. Animal Testing

To assess the valve’s in vivo performance, the research team conducted experiments on a rat model. During the experiment, saline was injected into the lateral ventricle of the rat to simulate elevated ICP. The valve was then inserted into the cisterna magna (CM) to observe its effect on ICP regulation. The results showed that in the untreated state, the ICP increased by more than 20 mmHg from baseline to peak, whereas in the treated state, the ICP increase remained below 5 mmHg, indicating that the valve effectively drained excess CSF and reduced ICP.

Conclusions and Significance

This study successfully developed a miniaturized PDMS duckbill valve capable of regulating CSF flow and reducing ICP. Through benchtop testing and animal experiments, the research team validated the valve’s unidirectional flow characteristics and low leakage rate. The simplicity of the valve’s design allows for precise control of the cracking pressure by adjusting key parameters such as the width of the fluid channel and the bill length, making it adaptable to the needs of individual patients. Compared to traditional shunt systems, this miniaturized valve offers higher reliability and lower risk of complications.

Research Highlights

1. Innovative Design: This study proposes a novel miniaturized duckbill valve that can be implanted within the cranium, mimicking the function of arachnoid granulations to provide a more natural CSF drainage pathway.
2. Precise Control: By adjusting the geometric parameters of the valve, the researchers were able to precisely control the cracking pressure, making it adaptable to the physiological needs of different patients.
3. In Vivo Validation: Animal experiments demonstrated that the valve effectively reduced ICP, confirming its feasibility and effectiveness in vivo.

Future Research Directions

Although this study achieved initial success, several issues require further investigation. For example, the long-term implantation performance of the valve, material durability, and testing in larger animal models. Additionally, the research team plans to develop a wireless telemetry system for real-time monitoring of ICP changes to further optimize the valve’s design and performance.

Summary

This study provides a new solution for the treatment of hydrocephalus. Through the design and testing of a miniaturized duckbill valve, the research demonstrated its potential in regulating ICP. This research not only holds significant scientific value but also offers new insights for future clinical applications.