(676f) Optimal Design and Layout of an Immunoassay on a Chip

Advances in microfluidics have inspired novel designs of LoC systems with integrated functionality and improved thermal and mass transfer characteristics. LoC systems have numerous applications in biochemical analysis [1], such as analysis of drugs in biological fluids, DNA separation and detection, and immunoassay. The application of LoC to immunoassay is a newly developing field showing considerable advantages [2]. The immunoassay method uses a homogeneous phase immunoreaction, followed by a electrophoretic separation step to isolate and analyze the reactants and products.

While the advantages of microfluidic systems have been demonstrated [3], systematic design methods are only beginning to emerge [4]. Most often, to design a LoC device with optimized layout geometry and performance, the designer is reduced to using trial-and-error approaches that involve a large number of experimental tests and long development cycles. This deficiency becomes even more acute when large scale microfluidic integration is needed [5].

To automate the process of LoC design, we have first implemented a computer-based simulation approach for general LoCs. The simulator contains modules [6] for the functional subsystems: mixing, reaction, injection, and separation. This simulator is used as the inner design loop, that is to evaluate any particular layout instance of the system of unit operations. This simulator has 3 important attributes:

(1) speed: we may evaluate more than 10 LoCs per second;

(2) accuracy: our modules have been verified to be within 10% of FEM simulations;

(3) flexibility: the LoC unit operations have been parametrized and may be invoked with arbitrary sizes and reasonable shapes.

Currently, we are able to incorporate the simulator in our automated LoC design methodology. To design a more compact LoC, different channel geometries are studied in literature [7], such as using the serpentine channel design and adopting various channel width. On the other hand, micro fabrication techniques favor simple channel geometry. In this presentation, we focus on a detailed comparison between different on-chip channel geometries for systems with reaction, injection and separation. Specifically, we seek to answer two questions: (1) how does the channel geometry affect chip performance and size, and (2) how do we chose an optimal topology with associated size.

[1] Bilitewski U, Genrich M, Kadow S. Biochemical analysis with microfluidic systems. Anal.Bioanal.Chem. 2003, 377:556-569

[2] Schultz NM, Huang L, Kennedy RT. Capillary electrophoresis-based immunoassay to determine insulin content and insulin secretion from single islets of Langerhans. Anal.Chem. 1995, 67:924-929.

[3] Ehrfeld W, Hessel V, Lehr H. Microreactors: New Technology for Modern Chemistry. 2000, Wiley-VCH.

[4] Pfeiffer AJ, Mukherjee T, Hauan S. Simultaneous design and placement of multiplexed chemical processing systems on microchips. 2004, Proceeding of ICCAD, 229-236

[5] Harrison DJ, Skinner C, Cheng SB. From Micro-Motors to Micro-Fluidics. 1997, International Conference on Solid-State Sensors and Actuators. 40-44.

[6] Pfeiffer AJ, Mukherjee T, Hauan S. Synthesis of multiplexed biofluidic microchips. In press for IEEE transactions on Computer-Aided Design of Integrated Circuits and Systems: Special Issue on design automation tools for microfluidic-based biochips. 2005

[7] Paegel BM, Hutt LD, Simpson PC, Mathies RA. Turn geometry for minimizing band broadening in microfabricated capillary electrophoresis channels. Anal.Chem. 2000, 72:3030-3037