Development of microfluidic calorimeter for radiation dosimetry

Abstract

Cancer is the greatest disease humanity has to overcome in this generation. The number of domestic cancer patients who visited the hospital for cancer treatment until 2016 was about 1.6 million and the number of registered cancer patients has steadily increased to about 220,000 as of 2016 (National Cancer Information Center). The increase in medical care expenditure related to cancer treatment is remarkable and it is growing more than 20% annually. The cost directly or indirectly related to cancer treatment by 2016 was 16.7 trillion won, which is 34.6 % of the total socio-economic cost of top ten diseases causing death. Radiation therapy, one of the three cancer treatment methods along with surgery and chemotherapy, utilizes strong permeability of X-ray, gamma ray, and particle beam to destroy the DNA and membrane of cancer cells. Since radiation has non-invasive nature of the lesions, there is fewer side effects and fewer sequelae than other treatments. However, since radiation therapy uses a high dose of more than 20 Gy, which is much higher than the fatal dose of 7 Gy in the human body, the delivery dose has to be accurately matched with the doctor’s prescription dose. This accurate match protects normal tissue from adverse side effects caused by overexposure of high doses which increases the success rate of radiation therapy. In particular, as the demand for medical diagnosis and treatment of diseases using radiation has increased recently, it is necessary to develop a base technology and a dose evaluation technology for measuring the absorbed dose of the therapeutic radiation to the human body more accurately. Internationally, the World Health Organization (WHO) has recommended a dose accuracy of less than 5% for radiation therapy and the American Association of Physicist in Medicine (AAPM) reports that the measurement uncertainty of absorbed dose should be less than 3% for this treatment accuracy. Therefore, to achieve such precision in the medical field, it is necessary to establish a direct measurement method using a calorimeter, in which the measurement uncertainty of the absorbed dose is less than 1%, and to use this to measure the absorbed dose in water. The absorbed dose in the human body can alternatively evaluate the absorbed dose to water which accounts for more than 70% of the human body. TRS-398 of the International Atomic Energy Agency (IAEA) or TG-51 of the American Association of Physicist in Medicine (AAPM) are international protocols based on water absorbed dose measurements. These are the standards to decide water absorbed dose against therapeutic radiation using ionization chamber calibrated by $^{60}Co$ gamma-ray standards. National standards institutions in some developed countries (15 countries) have developed graphite or water calorimeters to establish national standards for water absorbed dose and, based on these, supply water absorbed dose values to the agencies by accordance with IAEA TRS-398 or AAPM TG-51. However, in radiotherapy equipment, the treatment dosimetric conditions are very different from the standard calibration conditions. Furthermore, for precise radiation therapy with small beam size (less than $2 \times 2 cm^2$), such as a pencil beam, the ionization chamber calibrated in standard radiation field is not accurate enough to determine the water-absorbed dose (R. Alfonso et. al., “A new formalism for reference dosimetry of small and nonstandard fields”, Med. Phys. 35 (11)). Therefore, it is necessary to establish an international standard and an absolute dosimeter for measuring the absorbed dose for such a small radiation field. In this study, a microfluidic calorimeter was firstly fabricated with a water volume of $0.5 \times 0.5 \times 0.1 mm^3$, to measure the water absorbed dose in small field radiation accurately. The selection of the temperature sensor is very important since the absorbed dose using a calorimeter can be determined by measuring the temperature change of the medium. In this study, vanadium oxide ($VO_x$) was used as a temperature sensor material. In particular, vanadium dioxide ($VO_2$) and vanadium pentoxide ($V_2O_5$), which are representative materials, are one of the materials used in microbolometer applications due to their small 1/f noise and large TCR. The deposition and crystallization processes were optimized to obtain the desired vanadium oxide property for radiation dose measurement. As a result, it was confirmed by XRD, SEM and TCR measurement that $V_2O_5$ was well formed under sputter deposition conditions of gas flow rate ratio, Ar:$O_2$=4:1, and annealing temperature, 400 $^\circ C$. Especially, it was confirmed that TCR had a high-temperature sensitivity of -3.4 %/K. In this study, a heat conduction MEMS calorimeter was developed using an optimized temperature sensor. The SU-8 photoresist absorber is designed to be integrated on one of the two membranes in the chip calorimeter. When the radiation is irradiated, the $V_2O_5$ temperature sensor measures the temperature change as a result of the radiation energy absorbed by the SU-8 absorber. We confirmed the change of the calorimeter signals according to the various dose rates by using the linear accelerator, which is the therapeutic X-ray generator. The temperature change versus dose rate curve is fitted to be linear, which demonstrates the feasibility of a MEMS calorimeter as a radiation sensor. In this study, we developed a heat compensation microfluidic calorimeter for absorbed dose measurement against small field radiation. The area of the small radiation field is ~ mm scale, and the size of the water absorber on the microfluidic calorimeter is $500 \mu$m \times 500 \mum$, which is small enough to increase the measurement accuracy. Also, the heat compensation system was applied on the microfluidic chip by referring to the conventional large-scale graphite calorimeter measurement system. Joule heating and visible light irradiation experiments confirmed the heat compensation and succeeded in measuring the dose of 4 mm diameter radiation beam by Gamma knife radiotherapy machine. Although the radiation dose measurements demonstrated in this study did not reach the level of portable absolute dosimetry devices to replace large-scale graphite calorimeters or water calorimeters, it was the world's first attempt to develop a small radiation dose measurement platform using MEMS process. There is great significance in that point of view. If this is improved in the future, and if the calorimeter is manufactured in the form of a cantilever, it is expected to contribute to cost reduction and improvement of treatment accuracy in radiotherapy.