Microfluidic calorimeter for absolute dosimetry Jonghyun Kim1 and Wonhee Lee1* 1Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology (KAIST), Korea

ABSTRACT For radiation treatments, the accurate measurement of an absorbed dose of radiation is essential to reduce side effects. Herein, we present a microfluidic chip calorimeter integrated with water medium and vanadium oxide (VOx) thermistor. Microfluidic chip calorimeter can be a novel candidate for absolute dosimetry, providing high spatial resolution with small detector size and self-calibration capability. VOx thermistor provides high temperature resolution of 42 µK. The device thermal insulation is enhanced with vacuum thermal insulation and the resulting thermal conductance was 23 µW/K.

KEYWORDS: Chip calorimeter, Absolute dosimetry, Vanadium oxide thermistor

INTRODUCTION A radiation dosimeter is a tool for measuring the dose of ionizing radiation. To treat cancer patients, external radiation therapies have been developed for several years and they require the radiation dosimeters to plan the dose accurately to deposit optimal quantity of radiation over cancer cells. Among multiple radiation dosimeters, the calorimetry-based dosimeter is an international standard designated by Bureau International des Poids et Mesures (BIPM). Calorimetric dosimeters measure the temperature variation of absorbing media, in which the radiation energy is imparted, therefore enables absolute dosimetry. Recently, a small field radiation therapy facilitates precise treatment of tumors, utilizing a steep dose gradient at an interface, to reduce damages to the normal cells surrounding the target tumor cells. Unfortunately, the dose measurement for the small field radiation has a high measurement uncertainty due to volume averaging, which can be minimized by reducing the detector size[1,2]. Several groups demonstrated calorimeters with millimeter-sized detectors. Duane et al. designed the calorimetric dosimeter employing graphite media size with 2.5 mm diameter[3]. Renaud et al. also showed cylindrical graphite detector with 6 mm diameter and 10 mm height[4]. In this study, we fabricated a water calorimeter[5] and miniaturized detector size as small as 500 µm × 500 µm. Vanadium oxide (VOx) thermistor is adopted for the temperature sensor, which provides high sensitivity with high temperature coefficient of resistance (TCR) as well as low 1/f noise. Vacuum insulated parylene microfluidics provides high thermal insulation and reliable water reservoir.

EXPERIMENTAL Multiple microelectromechanical system(MEMS) fabrication processes were employed for calorimeter fabrication (Figure 1). The fabrication processes are mostly adopted from a previous realization of microfluidic calorimeter[5], except that the thermocouple is replaced with a thermistor. On a silicon nitride wafer, gold and VOx thin film were sputtered to form electrodes and thermistors in sequence. The deposited VOx was annealed in the furnace over 240℃ for crystallization. The parylene microfluidic channel was constructed by a conventional method using photoresist sacrificial layer. The parylene on the sides of sensing region was etched away by Reactive ion etching (RIE) to improve thermal insulation by making suspended bridge shape. Then the backside of Si was released, and SiN exposed at the previous parylene etch step was removed forming two bridge holes. The water as absorbing medium was injected and sealed inside the parylene channel. Figure 1(b) shows the calorimeter device. The device consists of four thermistors, measurement and control microfluidic chambers on separate suspended membranes. The parylene chambers for absorbing media are 500 μm × 500 μm × 20 μm (width × length × height) and located directly above the thermistors. The thermal insulation was enhanced by adopting vacuum insulated parylene microfluidics and the bridge

th 978-0-9798064-8-3/µTAS 2015/$20©15CBMS-0001 1867 19 International Conference on Miniaturized Systems for Chemistry and Life Sciences October 25-29, 2015, Gyeongju, KOREA structure. In Figure 1(d), the distorted shape at the sensor region was caused by intrinsic stress mismatch between parylene and SiN. The water was filled inside the parylene channel as shown in Figure 1(e).

Figure 1: (a) The fabrication procedure of the calorimeter. (b-d) The optical microscope images of the calorimeter. (b) Top view. (c) VOx thermistor. (d) Bridge structure for vacuum thermal insulation. Etched region is indicated with white arrow. (e) Parylene microfluidic channel filled with water.

RESULTS AND DISCUSSION To make V2O5 thin film thermistor, sputter and annealing condition was investigated. VOx thin film was sputter-deposited at 1 mTorr chamber pressure with Ar (20sccm) and O2 (5sccm) flow. At this stage, VOx atoms were randomly distributed amorphous phase, showing electrically insulating characteristic. Crystallization at 400℃ in air environment was followed directly after the deposition providing the nature of thermometer. The VOx crystalline structure was analyzed via X-ray diffractometer (XRD) and the thermistor resistance was measured on the heating stage. In Figure 2(a), the XRD result of the crystallized VOx phase was indicated by blue peaks, which perfectly matches with the peaks of reference V2O5. Also, the highest intensity peak at 2θ=20° represents (001) direction of orthorhombic V2O5 crystal structure, which is the preferred orientation of V2O5. The negative temperature coefficient of resistance (TCR) of the device was -2.9% (Figure 2b). With the resistance of 300 kΩ at room temperature, the temperature resolution was 42 µK assuming the noise is limited by thermal noise of the thermistor.

Figure 2: (a) XRD result of the fabricated V2O5 thin film. (b) Resistance v.s. temperature graph. TCR: -2.9%.

In figure 3(a), the calorimeter was calibrated using two out of four thermistors, one acting as a sensor and the other as a heater. The heating was on for an enough time and the applied voltage on the heater was off after the temperature was fully stabilized, which ensures that the thermistor resistance does not change and the applied power can be calculated accurately. 89 µW and 98 µW of the power was applied for air and vacuum condition respectively, inducing 0.84 K and 4.3 K of the temperature change. The thermal conductance of device was 23 µW/K at 40 mTorr, which was less than quarter of the thermal conductance in air environment (100 µW/K, Figure 3a). Figure 3(b) represents radiation measurement setup. The water is filled in the microfluidic chamber only at the measurement region, and not at the control region. Using a Wheatstone bridge circuit, output

1868 voltage difference between measurement and control is measured. The radiation absorbed dose (Dm) can be calculated by equation (1), where cm is the specific heat of the water, or absorbing media, and kHD is the heat defect.

= /(1 ) (1)

𝐷𝐷𝑚𝑚 𝑐𝑐𝑚𝑚∆𝑇𝑇 − 𝑘𝑘𝐻𝐻𝐻𝐻

Figure 3: Wheatstone bridge circuit for device calibration and sensor response to electrical heating. Schematic rep- resentation of radiation dose measurement.

CONCLUSION The V2O5 thermistor integrated water calorimeter was fabricated to utilize in dose measurement for small field radiation. MEMS fabrication facilitated detector miniaturization to micrometer scale by integrating water medium with parylene microfluidic chamber and high-sensitivity thermistor. VOx thermistor provides high temperature resolution of 42 µK. The device thermal insulation is enhanced with vacuum insulation and the thermal conductance was 23 µW/K.

ACKNOWLEDGEMENTS This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIP) (No. NRF-2012R1A2A2A03046642).

REFERENCES [1] J.U. Wuerfel, “Dose measurement in small fields,” Medical physics international journal, 1, 81-90, 2013. [2] Das, Ding, and Ahnesjö, “Small fields: Nonequilibrium radiation dosimetry,” Med. Phys., 35, 206- 215, 2008. [3] S. Duane et al., “An absorbed dose calorimeter for IMRT dosimetry,” Metrologia, 49, S168-S173, 2012. [4] Renaud et al., “Development of a graphite probe calorimeter for absolute clinical dosimetry,” Med. Phys., 40, 020701-1-6, 2013. [5] Lee, W., et al., “High-sensitivity microfluidic calorimeters for biological and chemical applications,” PNAS., 106, 15225-15230, 2009.

CONTACT * W. Lee ; phone: +82-42-350-1117; [email protected]

1869