Noninvasive measurement of cerebrospinal fluid flow using an ultrasonic transit time flow sensor: a preliminary study.

OBJECT Mechanical failure-which is the primary cause of CSF shunt malfunction-is not readily diagnosed, and the specific reasons for mechanical failure are not easily discerned. Prior attempts to measure CSF flow noninvasively have lacked the ability to either quantitatively or qualitatively obtain data. To address these needs, this preliminary study evaluates an ultrasonic transit time flow sensor in pediatric and adult patients with external ventricular drains (EVDs). One goal was to confirm the stated accuracy of the sensor in a clinical setting. A second goal was to observe the sensor's capability to record real-time continuous CSF flow. The final goal was to observe recordings during instances of flow blockage or lack of flow in order to determine the sensor's ability to identify these changes. METHODS A total of 5 pediatric and 11 adult patients who had received EVDs for the treatment of hydrocephalus were studied in a hospital setting. The primary EVD was connected to a secondary study EVD that contained a fluid-filled pressure transducer and an in-line transit time flow sensor. Comparisons were made between the weight of the drainage bag and the flow measured via the sensor in order to confirm its accuracy. Data from the pressure transducer and the flow sensor were recorded continuously at 100 Hz for a period of 24 hours by a data acquisition system, while the hourly CSF flow into the drip chamber was recorded manually. Changes in the patient's neurological status and their time points were noted. RESULTS The flow sensor demonstrated a proven accuracy of ± 15% or ± 2 ml/hr. The flow sensor allowed real-time continuous flow waveform data recordings. Dynamic analysis of CSF flow waveforms allowed the calculation of the pressure-volume index. Lastly, the sensor was able to diagnose a blocked catheter and distinguish between the blockage and lack of flow. CONCLUSIONS The Transonic flow sensor accurately measures CSF output within ± 15% or ± 2 ml/hr, diagnoses the blockage or lack of flow, and records real-time continuous flow data in patients with EVDs. Calculations of a wide variety of diagnostic parameters can be made from the waveform recordings, including resistance and compliance of the ventricular catheters and the compliance of the brain. The sensor's clinical applications may be of particular importance to the noninvasive diagnosis of shunt malfunctions with the development of an implantable device.

A microfluidic chip for real-time studies of the volume of single cells.

We report a microfluidic chip that is capable of measuring volume changes in single cells in real-time. Single eukaryotic cells were immobilized in the sensing area and changes in volume in response to hypotonic challenges and drugs were measured using the electrical impedance method. Experiments on MDCK cells showed that the maximum swelling and the time course of swelling vary between individual cells following hypotonic stimulation. The microfluidic chip allows, rapid and convenient change of solutions, enabling detailed studies of various drugs and chemicals that may play important role in cell physiology at the single cell level.

Microfluidic chip to produce temperature jumps for electrophysiology.

We developed a microfluidic chip that provides rapid temperature changes and accurate temperature control of the perfusing solution to facilitate patch-clamp studies. The device consists of a fluid channel connected to an accessible reservoir for cell culture and patch-clamp measurements. A thin-film platinum heater was placed in the flow channel to generate rapid temperature change, and the temperature was monitored using a thin-film resistor. We constructed the thermal chip using SU-8 on a glass wafer to minimize the heat loss. The chip is capable of increasing the solution temperature from bath temperature (20 degrees C) to 80 degrees C at an optimum heating rate of 0.5 degrees C/ms. To demonstrate the ability of the thermal chip, we have conducted on-chip patch-clamp recordings of temperature-sensitive ion channels (TRPV1) transfected HEK293 cells. The heat-stimulated currents were observed using whole-cell and cell-attached patch configurations. The results demonstrated that the chip can provide rapid temperature jumps at the resolution of single-ion channels.