Multifunctional System-on-Glass for Lab-on-Chip applications.

Lab-on-Chip are miniaturized systems able to perform biomolecular analysis in shorter time and with lower reagent consumption than a standard laboratory. Their miniaturization interferes with the multiple functions that the biochemical procedures require. In order to address this issue, our paper presents, for the first time, the integration on a single glass substrate of different thin film technologies in order to develop a multifunctional platform suitable for on-chip thermal treatments and on-chip detection of biomolecules. The proposed System on-Glass hosts thin metal films acting as heating sources; hydrogenated amorphous silicon diodes acting both as temperature sensors to monitor the temperature distribution and photosensors for the on-chip detection and a ground plane ensuring that the heater operation does not affect the photodiode currents. The sequence of the technological steps, the deposition temperatures of the thin films and the parameters of the photolithographic processes have been optimized in order to overcome all the issues of the technological integration. The device has been designed, fabricated and tested for the implementation of DNA amplification through the Polymerase Chain Reaction (PCR) with thermal cycling among three different temperatures on a single site. The glass has been connected to an electronic system that drives the heaters and controls the temperature and light sensors. It has been optically and thermally coupled with another glass hosting a microfluidic network made in polydimethylsiloxane that includes thermally actuated microvalves and a PCR process chamber. The successful DNA amplification has been verified off-chip by using a standard fluorometer.

[1]  Jin-Woo Choi,et al.  Point-of-care testing (POCT) diagnostic systems using microfluidic lab-on-a-chip technologies , 2015 .

[2]  P. Placidi,et al.  Design and experimental characterization of thin film heaters on glass substrate for Lab-on-Chip applications , 2015 .

[3]  Domenico Caputo,et al.  New a-Si:H two-terminal switching device for active display , 1996 .

[4]  P. Abgrall,et al.  Lab-on-chip technologies: making a microfluidic network and coupling it into a complete microsystem—a review , 2007 .

[5]  I-Ming Hsing,et al.  Microfabricated PCR-electrochemical device for simultaneous DNA amplification and detection. , 2003, Lab on a chip.

[6]  Domenico Caputo,et al.  Lab-on-chip system combining a microfluidic-ELISA with an array of amorphous silicon photosensors for the detection of celiac disease epitopes , 2015 .

[7]  Peter J. Asiello,et al.  Miniaturized isothermal nucleic acid amplification, a review. , 2011, Lab on a chip.

[8]  S. Quake,et al.  Monolithic microfabricated valves and pumps by multilayer soft lithography. , 2000, Science.

[9]  Wenbin Cao,et al.  Polydimethylsiloxane microfluidic chip with integrated microheater and thermal sensor. , 2009, Biomicrofluidics.

[10]  Alberto Escarpa,et al.  Real sample analysis on microfluidic devices. , 2007, Talanta.

[11]  Domenico Caputo,et al.  a‐Si:H temperature sensor integrated in a thin film heater , 2010 .

[12]  M. Heller.  DNA microarray technology: devices, systems, and applications. , 2002, Annual review of biomedical engineering.

[13]  Domenico Caputo,et al.  On-chip detection of multiple serum antibodies against epitopes of celiac disease by an array of amorphous silicon sensors , 2014 .

[14]  K. Mullis.  The unusual origin of the polymerase chain reaction. , 1990, Scientific American.

[15]  A.T. Pereira,et al.  Detection of Chemiluminescence Using an Amorphous Silicon Photodiode , 2007, IEEE Sensors Journal.

[16]  Fabrizio Palma,et al.  A novel a-Si:H mechanical stress sensor , 2003 .

[17]  Domenico Caputo,et al.  Amorphous Silicon p-i-n Structure Acting as Light and Temperature Sensor , 2015, Sensors.

[18]  M. DeRosa,et al.  Aptamer-based sandwich assay for on chip detection of Ochratoxin A by an array of amorphous silicon photosensors , 2016 .

[19]  Takatoki Yamamoto,et al.  PDMS-glass hybrid microreactor array with embedded temperature control device. Application to cell-free protein synthesis. , 2002, Lab on a chip.

[20]  D Caputo,et al.  Smart thin layer chromatography plate. , 2007, Lab on a chip.

[21]  A. Nascetti,et al.  Monitoring of Temperature Distribution in a Thin Film Heater by an Array of a-Si:H Temperature Sensors , 2012, IEEE Sensors Journal.

[22]  Domenico Caputo,et al.  Thermal characterization of thin film heater for lab-on-chip application , 2015, 2015 XVIII AISEM Annual Conference.

[23]  Yoshinori Yokoyama,et al.  Thermal micro pumps for a loop-type micro channel , 2004 .

[24]  D. Caputo,et al.  Electrical Properties of ITO/Crystalline-Silicon Contact at Different Deposition Temperatures , 2012, IEEE Electron Device Letters.

[25]  R. Gibbs.  DNA amplification by the polymerase chain reaction. , 1990, Analytical chemistry.

[26]  Patrick G. Herzog,et al.  Stacked amorphous silicon color sensors , 2002 .

[27]  Chunsun Zhang,et al.  PCR microfluidic devices for DNA amplification. , 2006, Biotechnology advances.

[28]  Dipak K. Sarker,et al.  Developments in microarray technologies. , 2003, Drug discovery today.

[29]  Yonghao Zhang,et al.  Microfluidic DNA amplification--a review. , 2009, Analytica chimica acta.

[30]  Domenico Caputo,et al.  Design and fabrication of microfluidics system integrated with temperature actuated microvalve , 2015 .

[31]  J. El-Ali,et al.  Simulation and experimental validation of a SU-8 based PCR thermocycler chip with integrated heaters and temperature sensor , 2004 .

[32]  Yong-Sang Kim,et al.  Development of PCR Microchip for Early Cancer Risk Prediction , 2011, IEEE Sensors Journal.