Thermal management of BioMEMS: temperature control for ceramic-based PCR and DNA detection devices

Integrated microfluidic devices for amplification and detection of biological samples that employ closed-loop temperature monitoring and control have been demonstrated within a multilayer low temperature co-fired ceramics (LTCC) platform. Devices designed within this platform demonstrate a high level of integration including integrated microfluidic channels, thick-film screen-printed Ag-Pd heaters, surface mounted temperature sensors, and air-gaps for thermal isolation. In addition, thermal-fluidic finite element models have been developed using CFDRC ACE+ software which allows for optimization of such parameters as heater input power, fluid flow rate, sensor placement, and air-gap size and placement. Two examples of devices that make use of these concepts are provided. The first is a continuous flow polymerase chain reaction (PCR) device that requires three thermally isolated zones of 94/spl deg/C, 65/spl deg/C, and 72/spl deg/C, and the second is an electronic DNA detection chip which requires hybridization at 35/spl deg/C. Both devices contain integrated heaters and surface mount silicon transistors which function as temperature sensors. Closed loop feedback control is provided by an external PI controller that monitors the temperature dependant I-V relationship of the sensor and adjusts heater power accordingly. Experimental data confirms that better than /spl plusmn/0.5/spl deg/C can be maintained for these devices irrespective of changing ambient conditions. In addition, good matching with model predictions has been achieved, thus providing a powerful design tool for thermal-fluidic microsystems.

[1]  M. A. Northrup,et al.  A Mems-based Miniature DNA Analysis System , 1995, Proceedings of the International Solid-State Sensors and Actuators Conference - TRANSDUCERS '95.

[2]  Larry J. Kricka,et al.  Thermal cycling and surface passivation of micromachined devices for PCR , 1995 .

[3]  D. Garling,et al.  Rapid cycle DNA amplification: time and temperature optimization. , 1991, BioTechniques.

[4]  Holger Becker,et al.  Microsystem technology in chemistry and life science , 1998 .

[5]  D. Garling,et al.  Minimizing the time required for DNA amplification by efficient heat transfer to small samples. , 1990, Analytical Biochemistry.

[6]  Anne R. Kopf-Sill,et al.  Commercialized and Emerging Lab-on-a-chip Applications , 2001 .

[7]  K. W. Hanck,et al.  A Novel Instrumental Approach To Digital Ac Voltammetry , 1992 .

[8]  C. Chou,et al.  Add ceramic "MEMS" to the pallet of microsystems technologies , 2001 .

[9]  M. A. Northrup,et al.  Functional integration of PCR amplification and capillary electrophoresis in a microfabricated DNA analysis device. , 1996, Analytical chemistry.

[10]  A Manz,et al.  Chemical amplification: continuous-flow PCR on a chip. , 1998, Science.

[11]  T. Yamane,et al.  High speed polymerase chain reaction in constant flow. , 1994, Bioscience, biotechnology, and biochemistry.

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

[13]  D. Ehrlich,et al.  A closed-cycle capillary polymerase chain reaction machine. , 2001, Analytical chemistry.

[14]  J. Estes,et al.  Integration of a receiver front-end in multilayer ceramic integrated circuit (MCIC) technology , 1997, Proceedings of 1997 Wireless Communications Conference.

[15]  Mingcong Gao,et al.  Micro heat pipes in low temperature cofire ceramic (LTCC) substrates , 2002, ITherm 2002. Eighth Intersociety Conference on Thermal and Thermomechanical Phenomena in Electronic Systems (Cat. No.02CH37258).

[16]  Daniel J. Sadler,et al.  Ceramic magnetohydrodynamic (MHD) micropump , 2001, MOEMS-MEMS.

[17]  H. Yowanto,et al.  Electronic detection of nucleic acids: a versatile platform for molecular diagnostics. , 2001, The Journal of molecular diagnostics : JMD.

[18]  C. Chou,et al.  A Miniaturized Cyclic PCR Device , 2001 .

[19]  Mario Ricardo Gongora-Rubio,et al.  Meso (Intermediate)-Scale Electromechanical Systems for the Measurement and Control of Sagging in LtcC Structures , 1998 .