Rajnish Changrani

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.

A miniaturized cyclic PCR device—modeling and experiments

Abstract With the aid of thermal and fluidic modeling using CFDRC ACE+™, we designed and fabricated the first miniaturized cyclic polymerase chain reaction (PCR) device in low-temperature cofired ceramics. The device comprises of a serpentine channel with different cross-sectional areas in different reactor zones to provide adequate residence time for the melting, annealing, and extension reaction to take place. This is in contrary to the thermal cycling in the batch PCR system. With a flow rate of 15 μl/min, the designed time to complete 30 PCR cycles is less than 40 min, given the total volume of the device 19 μl, provided an internal pump may be implemented to reduce the dead volume. We have demonstrated DNA amplification in this device, using an external peristaltic pump, and the PCR product was used with a DNA bioelectronic sensor chip (Motorola e-Sensors™) for genotyping experiment.

A Miniaturized Cyclic PCR Device

DNA amplification with polymerase chain reaction (PCR) is often performed in a batch process using a bench-top thermal cycler or in a micromachined PCR chamber. Recent effort has shown a continuous flow through PCR system can be realized by a time-space conversion in the PCR system [1]. Devices of this kind open up new areas of application in medical diagnostics, such as the online amplification and monitoring of a specific gene. Here we take advantage of the vertical integration capability of multi-layer ceramic technology and demonstrate a miniaturized cyclic PCR device. A cyclic device promises much smaller footprint and ease of integration into a micro total analysis system.

Add Ceramic “MEMS” to the Pallet of MicroSystems Technologies

Just as the 40+ years of technology developments associated with the electronic application of semiconductor fabrication processes is “morphing” into a micro-electro- mechanical systems (MEMS) technology in the past dozen years or so, so it seems may the “mature” multilayer ceramic fabrication technology associated with capacitor components and interconnect substrates for the integrated circuit industry, be morphed into MEMS – microsystems technology applications. This paper highlights work underway in Motorola Labs aimed at exploring the potential to develop 3D multilayer ceramic structures to integrate (monolithic and hybrid) multiple functions to create microsystems for wireless, energy and life science applications. By multiple functions, we refer to the ability for a microsystem to perform electronic, fluidic, thermonic, photonic and mechatronic (or actuator) based functions. Current capabilities of the multilayer ceramic materials and processes to achieve integrated functionalities for wireless applications will be described including the development of a new dielectric enabling increased performance for wireless applications. Also to be highlighted will be exploratory microscale fuel cell prototypes exploiting advances in the multilayer ceramic lamination and feature forming technologies enabling the insertion of 3D microchannels for microfluidic functions. These prototypes also feature the ability of the technology to provide thermonic functionality for microreactor devices. Feasibility of a light source that can be integrated into the technology platform hinting at photonic applications will be described. Many materials science and engineering advancements are needed to achieve the potential of this “old” but newly “morphing” technology and some of these will be noted.

Thermal management of BioMEMS

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 allow 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 dependent I-V relationship of the sensor and adjusts heater power accordingly. Experimental data confirms that better than +/- 0.5/spl deg/C can be maintained for these devices irrespective of changing ambient conditions. In addition, excellent matching with model predictions has been achieved, thus providing a powerful design tool for thermal-fluidic microsystems.

Ceramic magnetohydrodynamic (MHD) micropump

Magnetohydrodynamic (MHD) pumping has several attractive features including no-moving-parts operation, compatibility with biological solutions, and bi-directional pumping capability. In this work, a re-circulating ceramic MHD micropump is described. The MHD operation principle is based on the generation of Lorenz forces on ions within an electrolytic solution by means of perpendicular electric and magnetic fields. These Lorenz forces propel the ions through a channel, thus creating a net flow with no moving parts. Fabrication of the pumps is achieved by means of a new ceramic MEMS (CMEMS) platform in which devices are built from multiple layers of green-sheet ceramics. The major advantage to this technology is that unlike many other fabrication technologies, the multi-layer ceramic CMEMS platform is truly three-dimensional, thus enabling the building of complex integrated systems within a single platform. The ceramic-based MHD pumps have been analyzed and tested using both finite element modeling and experimental validation. Test results indicate that the pumps are capable of pumping a wide range of biological fluids in the flow rate range of microliters per minute. Additionally, good stability over 24 hours and good correlation with modeling data have been verified.