Microfabricated Temperature-Sensing Devices Using a Microfluidic Chip for Biological Applications
Naoki Inomata†, Masaya Toda, and Takahito Ono
Graduate School of Engineering, Tohoku University
6-6-01 Aza-Aoba, Aramaki, Aoba, Sendai, Miyagi 980-8579, Japan
Microelectromechanical systems (MEMS) and micrototal analysis systems (μTAS) have been developed using microfabrication technologies. As MEMS and μTAS contribute to smaller, higher-performance, less expensive, and integrated sensing techniques, they have been applied in many fields. In this paper, we focus on microfabricated thermal detection devices, including a microthermistor fabricated using vanadium oxide (VOx) and a resonant thermal sensor integrated into a microfluidic chip, and we present the research work we have done into biological applications, applications using a unique material and detection method for liquid samples. The VOx thermistor, which has a high temperature coefficient of resistance at –1.3%/K, is mounted onto a thermally insulated membrane in the microfluidic chip. This device is used to detect glucose and cholesterol concentrations in solutions. The resonant thermal sensor is another candidate for obtaining highly sensitive thermal measurements; however, this sensor is difficult to use with liquids because of vibration damping and thermal loss. To solve these problems, we propose a partial vacuum packaging system for the sensor in the microfluidic chip. This technique, which involves silicon resonators, was used to successfully detect the heat from a single brown fat cell. Moreover, the possibility of using a VOx resonant thermal sensor is discussed. The future prospects for MEMS and automation technology are described, with a focus on the Internet of Things/big data for medical and healthcare applications.
-  E. A. Olson, M. Y. Efremov, A. T. Kwan, S. Lai, V. Petrova, F. Schiettekatte, J. T. Warren, M. Zhang, and L. H. Allen, “Scanning calorimeter for nanoliter-scale liquid samples,” Appl. Phys. Lett., Vol.77, pp. 2671-2673, 2000.
-  K. Verhaegen, K. Baert, J. Simaels, and W. V. Driessche, “A high-throughput silicon microphysiometer,” Sens. Act., Vol.82, pp. 186-190, 2000.
-  E. A. Johannessen, J. M. R. Weaver, L. Bourova, P. Svoboda, P. H. Cobbold, and J. M. Cooper, “Micromachined nanocalorimetric sensor for ultra-low-volume cell-based assays,” Anal. Chem., Vol.74, pp. 2190-2197, 2002.
-  J. L. Garden, E. Chateau, and J. Chaussy, “Highly sensitive ac nanocalorimeter for microliter-scale liquids or biological samples,” Appl. Phys. Lett., Vol.84, pp. 3597-3599, 2004.
-  Y. Zhang and S. Tadigadapa, “Calorimetric biosensors with integrated microfluidic channels,” Biosens. Bioelectron., Vol.19, pp. 1733-1743, 2004.
-  E. B. Chancellor, J. P. Wikswo, and F. Baudenbachera, “Heat conduction calorimeter for massively parallel high throughput measurements with picoliter sample volumes,” Appl. Phys. Lett., Vol.85, pp. 2408-2410, 2004.
-  Y. Zhang and S. Tadigadapa, “Thermal characterization of liquids and polymer thin films using a microcalorimeter,” Appl. Phys. Lett., Vol.86, pp. 034101, 2004.
-  J. Lee, C. M. Spadaccini, E. V. Mukerjee, and W. P. King, “Differential scanning calorimeter based on suspended Membrane single crystal silicon microhotplate,” J. Microelectromechs., Vol.17, pp. 1513-1523, 2008.
-  L. Wang, B. Wang, and Q. Lin, “Demonstration of MEMS-based differential scanning calorimetry for determining thermodynamic properties of biomolecules,” Sens. Act. B, Vol.134, pp. 953-958, 2008.
-  W. Lee, W. Fon, B. W. Axelrod, and M. L. Roukes, “High-sensitivity microfluidic calorimeters for biological and chemical applications,” PNAS, Vol.106, pp. 15225-15230, 2009.
-  B. Davaji and C. H. Lee, “A paper-based calorimetric microfluidics platform for bio-chemical sensing,” Biosens Bioelectron., Vol.59, pp. 120-126, 2014.
-  B. Davaji, H. J. Bak, W. J. Chang, and C. H. Lee, “A novel on-chip three-dimensional micromachined calorimeter with fully enclosed and suspended thin-film chamber for thermal characterization of liquid samples,” Biomicrofluidics, Vol.8, pp. 034101, 2014.
-  A. K. Vutha, B. Davaji, C. H. Lee, and G. M. Walker, “A microfluidic device for thermal particle detection,” Microfluid Nanofluid., Vol.17, pp. 871-878, 2014.
-  A. Zylbersztejn and N. F. Mott, “Metal-insulator transition in vanadium dioxide,” Phys. Rev. B, Vol.11, pp. 4383-4395, 1975.
-  T. M. Rice, H. Launois, and J. P. Pouget, “Comment on” VO2: Peierls or Mott-Hubbard? A view from band theory,” Phys. Rev. Lett., Vol.73, pp. 3042, 1994.
-  S. Biermann, A. Poteryaev, A. I. Lichtenstein, and A. Georges, “Dynamical singlets and correlation-assisted Peierls transition in VO2,” Phys. Rev. Lett., Vol.94, pp. 026404, 2005.
-  V. Eyert, “VO2: A novel view from band theory,” Phys. Rev. Lett., Vol.107, pp. 016401, 2011.
-  J. F. De Natale, P. J. Hood, and A. B. Harker, “Formation and characterization of grain-oriented VO2 thin films,” J. Appl. Phys., Vol.66, pp. 5844-5850, 1989.
-  S. J. Jiang, C. B. Ye, M. S. R. Khan, and C. G. Granqvist, “Evolution of thermochromism during oxidation of evaporated vanadium films,” Appl. Opt., Vol.30, pp. 847-851, 1991.
-  E. E. Chain, “The influence of deposition temperature on the structure and optical properties of vanadium oxide films,” J. Vac. Sci. Technol. A, Vol.4, pp. 432-435, 1986.
-  M. Gurvitch, S. Luryi, A. Polyakov, A. Shabalov, M. Dudley, G. Wang, S. Ge, and V. Yakovlev, “VO2 films with strong semiconductor to metal phase transition prepared by the precursor oxidation process,” J. Appl. Phys., Vol.102, pp. 033504, 2007.
-  C. Chen, X. Yi, X. Zhao, and B. Xiong, “Characterizations of VO2-based uncooled microbolometer linear array,” Sens. Act. A, Vol.90, pp. 212-214, 2001.
-  M. Kohin and N. R. Butler, “Performance limits of uncooled VOx microbolometer focal plane arrays,” Proc. SPIE 2004, Vol.5406, pp. 447-453, 2004.
-  Y. H. Han, K. T. Kim, H. J. Shin, S. Moon, and I. H. Choi, “Enhanced characteristics of an uncooled microbolometer using vanadium-tungsten oxide as a thermometric material,” Appl. Phys. Lett., Vol.86, pp. 254101, 2005.
-  N. Chi-Anh, H. J. Shin, K. Kim, Y. H. Han, and S. Moon, “Characterization of uncooled bolometer with vanadium tungsten oxide infrared active layer,” Sens. Act. A, Vol.123-124, pp. 87-91, 2005.
-  N. Chi-Anh and S. Moon, “Excess noise in vanadium tungsten oxide bolometric material,” Infrared Physics & Technology, Vol.50, pp. 38-41, 2007.
-  H. Wada, M. Nagashima, T. Shima, M. Hijikawa, and N. Oda, “256×256 uncooled microbolometer focal plane array,” T. IEE Japan, Vol.117-E, No.12, pp. 612-616, 1997.
-  N. Inomata, L. Pan, Z. Wang, M. Kimura, and T. Ono, “Vanadium oxide thermal microsensor integrated in a microfluidic chip for detecting cholesterol and glucose concentrations,” Microsyst Technol, Vol.23, pp. 2873-2879, 2016.
-  A. Kumar, R. Malhotra, B. D. Malhotra, and S. K. Grover, “Co-immobilization of cholesterol oxidase and horseradish peroxidase in a sol-gel film,” Analytica. Chimica. Acta., Vol.414, pp. 30-50, 2000.
-  J. R. Barnes, R. J. Stephenson, C. N. Woodburn, S. J. O’Shea, M. E. Welland, T. Rayment, J. K. Gimzewski, and C. Gerber, “A femtojoule calorimeter using micromechanical sensors,” Rev. Sci. Instrum., Vol.65, pp. 3793-3798, 1994.
-  S. J. Kim, T. Ono, and M. Esashi, “Thermal imaging with tapping mode using a bimetal oscillator formed at the end of a cantilever,” Rev. Sci. Instrum., Vol.80, pp. 033703, 2009.
-  N. Inomata, M. Toda, M. Sato, A. Ishijima, and T. Ono, “Pico calorimeter for detection of heat produced in an individual brown fat cell,” Appl. Phys. Lett., Vol.100, pp. 154104, 2012.
-  M. Toda, N. Inomata, and T. Ono, “Bimorph cantilevers actuated by focused laser from side,” IEEJ Trans. on Sensors and Micromachines, Vol.131, pp. 327-331, 2011.
-  M. Toda, T. Ono, F. Liu, and I. Voiculescu, “Evaluation of bimaterial cantilever beam for heat sensing at atmospheric pressure,” Rev. Sci. Instrum., Vol.81, pp. 055104, 2010.
-  N. Inomata, M. Toda, and T. Ono, “Highly sensitive thermometer using a vacuum packed Si resonator in a microfluidic chip for the thermal measurement of single cells,” Lab chip, Vol.16, pp. 3597-3603, 2016.
-  D. W. Allan, “Time and frequency (time-domain) characterization, estimation, and prediction of precision clocks and oscillators,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control, Vol.34, pp. 647-654, 1987.
-  J. Nedergaard, B. Cannon, and O. Lindberg, “Microcalorimetry of isolated mammalian cells,” Nature, Vol.267, pp. 518-520, 1997.
-  T. Yahata and A. Kuroshima, “Influence of endocrine and chemical factors on glucagoninduced thermogenesis in brown adipocytes,” Jpn J. Physiol., Vol.32, pp. 303-307, 1982.
-  D. G. Clark, M. Brinkman, and S. D. Neville, “Microcalorimetric measurements of heat production in brown adipocytes from control and cafeteria-fed rats,” Biochem. J., Vol.235, pp. 337-342, 1986.
-  B. Pettersson, “CO2-mediated control of fatty acid metabolism in isolated hamster brown-fat cells during norepinephrine stimulation,” Eur. J. Biochem., Vol.72, pp. 235-240, 1977.
-  M. Sato, M. Toda, N. Inomata, H. Maruyama, Y. Okamatsu-Ogura, F. Arai, T. Ono, A. Ishijima, and Y. Inoue, “Temperature changes in brown adipocytes detected with a biomaterial microcantilever,” Biophys. J., Vol.106, pp. 2458-2464, 2014.
-  C. Gota, K. Okabe, T. Funatsu, Y. Harada, and S. Uchiyama, “Hydrophilic fluorescent nanogel thermometer for intracellular thermometry,” J. Am. Chem. Soc., Vol.131, pp. 2766-2767, 2009.
-  K. Okabe, N. Inada, C. Gota, Y. Harada, T. Funatsu, and S. Uchiyama, “Intracellular temperature mapping with a fluorescent polymeric thermometer and fluorescence lifetime imaging microscopy,” Nat. Commun., Vol.3, pp. 705-712, 2012.
-  M. Suzuki, V. Tseeb, K. Oyama, and S. Ishiwata, “Microscopic detection of thermogenesis in a single HeLa cell,” Biophys. J., Vol.92, pp. L46-L48, 2007.
-  Y. Takei, S. Arai, A. Murata, M. Takabayashi, K. Oyama, S.Ishiwata, S. Takeoka, and M. Suzuki, “A nanoparticle-based ratiometric and self-calibrated fluorescent thermometer for single living cells,” ACS Nano, Vol.8, pp. 198-206, 2014.
-  C. Cabuz, “Silicon micromachined resonators for sensor applications,” Ph. D. thesis of Graduate School of Engineering, Tohoku University, 1994.
-  A. Holsteen, I. S. Kim, and L. J. Lauhon, “Extraordinary dynamic mechanical response of vanadium dioxide nanowires around the insulator to metal phase transition,” Nano Lett., Vol.14, pp. 1898-1902, 2014.
-  N. Inomata, L. Pan, M. Toda, and T. Ono, “Temperature-depended mechanical properties of microfabricated vanadium oxide mechanical resonators for thermal sensing,” Jpn. J. Appl. Phys., Vol.55, pp. 037201, 2016.
-  A. K. Au, N. Bhattacharjee, L. F. Horowitz, T. C. Chang, and A. Folch, “3D-printed microfluidic automation,” Lab Chip, Vol.15, pp. 1934, 2015.
-  F. Sassa, J. Fukuda, and H. Suzuki, “Microprocessing of liquid plugs for bio/chemical analyses,” Anal. Chem., Vol.80, pp. 6206-6213, 2008.
-  R. Riahi, S. A. M. Shaegh, M. Ghaderi, Y. S. Zhang, S. R. Shin, J. Aleman, S. Massa, and D. Kim, “Automated microfluidic platform of bead-based electrochemical immunosensor integrated with bioreactor for continual monitoring of cell secreted biomarkers,” Sci. Rep., Vol.6, pp. 24598, 2016.
-  A. R. Wu, J. B. Hiatt, R. Lu, J. L. Attema, N. A. Lobo, I. L. Weissman, M. F. Clarke, and S. R. Quake, “Automated microfluidic chromatin immunoprecipitation from 2,000 cells,” Lab Chip., Vol.9, pp. 1365-1370, 2009.
-  M. Hagiwara, T. Kawahara, T. Iijima, and F. Arai, “High-speed magnetic microrobot actuation in a microfluidic chip by a fine V-groove surface,” IEEE Trans. Robot., Vol.29, pp. 363-372, 2013.
-  T. Hayakawa, S. Fukada, and F. Arai, “Fabrication of an on-chip nanorobot integrating functional nanomaterials for single-cell punctures,” IEEE Trans. Robot., Vol.30, pp. 59-67, 2014.
-  L. Feng, P. Di, and F. Arai, “High-precision motion of magnetic microrobot with ultrasonic levitation for 3-D rotation of single oocyte,” Int. J. Robot. Res., pp. 1-14, 2016.
-  T. Kawahara, M. Sugita, M. Hagiwara, F. Arai, H. Kawano, I. Shihira-Ishikawa, and A. Miyawakie, “On-chip microrobot for investigating the response of aquatic microorganisms to mechanical stimulation,” Lab Chip, Vol.13, pp. 1070-1078, 2013.
-  H. Sugiura, S. Sakuma, M. Kaneko, and F. Arai, “On-chip method to measure mechanical characteristics of a single cell by using moiré fringe,” Micromachines, Vol.6, pp. 660-673, 2015.
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