Ask the Expert: Lab-on-a-chip, have it their way or your way?

Microfluidic lab-on-a-chip systems (also known as biochips) are rapidly transforming the drug discovery validation and development process by providing an enabling platform for diagnostics, genomics, proteomics, metabolomics and high throughput screening. In addition, microfluidics is also finding use in devices for clinical diagnostics, environmental monitoring and detection of toxins for homeland security.

As applications of these devices expand, the design of these microsystems has evolved into a multidisciplinary field requiring expertise in materials, chemistry, biology and engineering. Given this broad scope, it is almost impossible to manually understand the complicated design factors that influence and limit system performance. This complexity means that design techniques based purely on experiments and intuition are prone to costly delays and failure.

Computer-aided design techniques based on 3-D numerical simulations have emerged as a promising alternative for the design of various components and subsystems of lab-on-a-chip devices. However, these approaches are computationally intensive, difficult to use, time-consuming, do not scale efficiently for more complex designs, and are generally unsuitable for system-level design. Present design tools are inadequate where fast response and ease of use will be two major considerations. This has motivated the development of computer-aided design tools that can rapidly simulate the complex underlying phenomena to predict system performance of microfluidic devices without significantly compromising accuracy.

Demanding innovative design

Figure 1: Design Automation approach to Lab-on-a-Chip devices showing System Simulation Software as the heart of this approach

The demand for better performing complex systems necessitates that design automation innovations enable integration of design and fabrication processes to an extent now taken for granted in the semiconductor industry. To achieve this level of integration between design and fabrication, there is a need for a design environment that links all the key steps in the workflow for biochip development – concept generation, design optimization, layout generation, and prototype fabrication, and brings all of the diverse technologies together for faster translation from “concept to prototype to production”.

Current commercial practice is to offer standardized chips for development and in many cases production. The chip has a designated function regardless of its purpose. This standardized design stifles the usefulness and widespread application of biochip techniques and is not cost effective or timely for product development. A design system that takes all of the design and performance requirements and couples it with available technology to create biochips rapidly and cost effectively would promote wider use of lab-on-a-chip devices.

The solution?

Pharos is a software package developed to meet this growing demand for custom solutions, and enable rapid design of application-specific lab-on-a-chip systems in a cost-effective manner. Pharos is designed to be the interface between the assay developer and the engineer and to become the front end for a seamless process from design to production.

The software integrates state-of-the art system simulation software with microfabrication calculations, design principles and databases to allow collaborative development of microfluidic devices using a computer-aided engineering approach. This unique mating of automation tools for both design and prototyping increases the competitive capability of companies developing microfluidic devices and small MEMS foundries, by accelerating and unifying the product development cycle. This approach has demonstrated a dramatic reduction in design time and allows a rational method to translate concepts into functional microfluidic layouts.

Pharos features a GUI-driven design automation environment, where a microfluidic device can be assembled on a computer as a network of components, and can be rapidly analyzed, reconfigured and optimized to satisfy process and manufacturing constraints. Subsequently, the software exports layouts into appropriate CAD formats (such as AutoCAD or bitmap-based images) for microfabrication using photolithography or other approaches. This approach substantially reduces the product development cycle and provides an affordable and rational method to translate innovative concepts into functional microfluidic devices.

Pharos: benefits and impact

Figure 2(a) shows the initial layout of the microfluidic chip. The chip features multiple bioprocessing functionalities (indicated by colored zones) – mixing/dilution and reaction (pink), electrokinetic injection (green), and electrophoretic separation and detection (red).

Pharos is suited for design of microfluidic chips for a variety of applications, including drug discovery, high throughput screening and clinical diagnostics. The software enables design of new microfluidic assay platforms, as well as translation of existing assays from a traditional microwell plates to a microfluidic platform. This creates a significant time and cost impact in the product and assay development process by allowing: (a) rapid screening of new concepts; (b) reduced physical prototyping and testing; (c) rational optimization of devices and processes; (d) improved understanding of device failure; (e) regulatory assistance; and (f) faster time to market with better and cost-effective products.

Pharos is trademark CFD Research Corporation, 2007.

Stephen F. Malin is Vice President for Biotechnology Commercialization at CFD Research Corporation in Huntsville, AL.