(K-435) Ultrasound-Interrogated Microfluidic for Diagnosis of Shunt Failure

Introduction:: Intracranial pressure (ICP) monitoring is essential for a wide variety of neurological conditions. For instance, ICP monitoring can be used to detect critically elevated pressure in hydrocephalus patients or be used to inform treatment decisions for patients with traumatic brain injuries or cancerous brain tumors. Unfortunately, measuring ICP is challenging and symptoms of elevated ICP are nonspecific (e.g., headache, nausea, fatigue), making the condition difficult to verify.

Existing diagnostic approaches include using MRI/CT scans to look for enlarged ventricles; however, these methods lack accuracy, are costly and time consuming, or expose patients to unnecessary radiation. Alternatively, deep probes can be used to measure pressure, but require an invasive surgical procedure that poses additional health risks to patients. To address these issues, we propose to interrogate a passive pressure sensor “target” with ultrasound to measure ICP and monitor for shunt failure.

Here we report on a completely redesigned readout approach that transduces increasing pressure into an easy to visualize series of bright “dots” that consecutively disappear in a B-mode ultrasound image. Our sensor consists of a fluid-filled, pressure-sensitive diaphragm that will be implanted into a burr hole in the skull. As intracranial pressure increases, fluid is displaced out of the diaphragm and into a serpentine microfluidic channel. When imaged with ultrasound, channel cross sections appear as bright signals (ON) when initially filled with air and disappear (OFF) when the channel is filled with water (Figure 1A).


Materials and Methods:: We tested the pressure sensitivity of our design using prototypes constructed from three bonded layers of poly-dimethyl-siloxane (PDMS). The PDMS was cast in molds fabricated with a Boston microfabrication printer (BMF microArch S140) and the smallest features, the channels visualized by the ultrasound, had a cross-section of 200 mm by 200 mm. As PDMS is clear, we filled the diaphragm layer with water that was dyed red for visibility (Figure 1A). Testing was performed by modulating the diaphragm pressure across physiologic values (0-55 mmHg) using an air-filled syringe pump with an inline pressure sensor. Our testing revealed that the sensitivity of the device could be increased by adding an air reservoir that allows for the air within the serpentine channel to be compressed as fluid is displaced at higher pressures.

To test the ultrasound visualization and readout, the prototype was placed within a burr hole in a model human skull with tissue mimicking phantom covering the top and bottom of the device (to reflect in-vivo conditions). Fluid displacement through the serpentine channel was imaged using a programable ultrasound system (Vantage 256, Verasonics) equipped with a linear array probe (L11-5, ATL) at 5 MHz transmitting frequency (Figure 1B). The diaphragm pressure was again modulated across physiological values (0-55 mmHg) using the same air-filled syringe pump setup (Figure 1C and D). The diaphragm pressure was modulated repeatedly ten times to ensure consistency, and critical displacements were recorded.


Results, Conclusions, and Discussions:: RESULTS

Our data confirms that the device operates as expected, and thereby confirms the viability of our new approach. Our B-mode images show clear, bright signals through tissue-mimicking phantoms, supporting our device’s ability to be imaged in-vivo. Additionally, our pressure to fluid displacement readings also support that our device produces consistent, repeatable readings. We were able to record the expected fluid displacement at critical physiological pressures. Future testing will include further calibration of fluid displacement at relevant pressures and lifetime testing of the device in in-vivo conditions.



DISCUSSION & CONCLUSION

The experimental results show that intracranial pressure can be monitored continuously in-vitro and provide strong feasibility data for later in-vivo work. On a broader scale, these results support a new paradigm of sound-interrogated physiological sensors, which solve RF-based telemetry, radiation, and invasiveness issues of prior devices. The traditional challenge with RF based devices is that increasing the stability and robustness of the device comes at the expense of sensitivity and reduces the ability of the device to transmit radiofrequency signals. Our novel approach solves these challenges by creating a topology that can be made thick enough to limit long-term diffusion in and out of the device for long-term stability, yet still be easily measured with standard tools available in the clinical setting.


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