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The Need for Precision Metrology in Microfluidics Research The Need for Precision Metrology in Microfluidics
Research
Posted: September 28th, 2005 12:34 PM EDT

Business Communications Co. Inc. (©2005 by Steve Werely)
Figure 1: Worldwide Market for Microfluidic Technologies.

The Cascade Microtech MFP Microport with MPM micropositioner.
The Cascade Microtech EBP Microport with MPM micropositioner.

Cali Sartor
The term microfluidics refers to any technology that moves microscopic and nanoscale quantities
of fluid through channels on a Micro Electro-Mechanical System (MEMS). Microfluidics
includes flow control, liquid handling, biochemical sensors, micro-arrays, lab-on-a-chip, and
particle-laden fluids.
While recent research and development in the field of microfluidics have fallen into both
biological and non-biological applications, according to Flowmap, Microfluidics Roadmap for
the Life Sciences (2004), the life sciences segment of microfluidics is the fastest growing
segment of the market. It is expected to grow at an annual rate of 30 percent per year with drug
discovery and medical diagnostic and therapeutic devices representing the most promising fields.
The life sciences segment of the microfluidics industry can be further segmented into three major
categories: drug discovery, medical diagnostics and therapeutics, and ecology. Cascade
Microtech (Beaverton, OR) has developed products that enable high-frequency (multi-gigahertz)
on-wafer measurements and on-wafer current measurements as low as one femtoamp.
Drug Discovery
The drug discovery and development process is time-consuming and costly the process can
typically take between 10-12 years from start of development to commercialization. Today, only
a rare few drugs meet the profit expectations of the pharmaceutical companies and these
"blockbuster" drug products make up approximately half of the revenue in the pharmaceutical
industry. Because of this trend, there is huge pressure on the drug companies and players in the
market to reduce costs.
Within the drug discovery process, there are an increasing number of microfluidics technologies
being developed and utilized, creating the opportunity for substantial improvement in the time
and cost of the drug discovery process.
One such opportunity exists with High Throughput Screening procedures where volumes per
assay continue to drop into the microliter and nanoliter ranges. Currently, the typical volume
used in mass screening falls below five microliters. This trend of miniaturization is common to
all microfluidic applications, and offers the opportunity to reduce the reagent and volume
samples as well as the reaction time involved in each experiment, thereby lowering the total cost-
per-experiment. Two of Cascade Microtech's L-series microports the MFP (Micro-Fluidic Port) and the EBP
(Electrode-Bio Port) are suitable for such applications.
The MFP is used for electroosmotic flow and electrophoresis experimentation. It eliminates the
need for test fixtures or manifolds, allowing scientists to spend more time working on
experiments and less time setting up. The EBP provides high-voltage electrode application for
electroosmotic pumping and electrophoresis. Its safe electrode interface to the device is non-
corrosive and non-obtrusive to solutions and reagents.
This shift into a microscale range of volumes brings a very different set of fluid dynamic
principles than that within the macroscale range, where viscosity and surface tension play a
much bigger role. Consequently, the need for precision and accuracy becomes extremely critical
to achieving the benefits of miniaturization. By addressing this need for precision in liquid
handling procedures, researchers can significantly improve the speed and cost of the drug
discovery stage of the development process.
Medical Diagnostics and Therapeutics
The largest market segment and market potential for BioMEMS-based technologies is found in
the field of medicine. Research in this segment can be categorized into two distinct branches of
study:
diagnostics, which is focused on monitoring the health state of a patient
therapeutics, which is focused on the treatment of a patient's condition.
Because of the substantial financial investment in the field of medical diagnostics, it holds the
greatest potential for benefiting from advancements in microfluidics.
With advances in microfluidics technologies, researchers will have the ability to utilize small
volumes of samples and reagents, which in turn reduces the total development cost of such in-
vitro or in-vivo devices. Additionally, the miniaturization of the reaction allows an accelerated
reaction time as well as the ability to integrate several protocol steps. In the end, companies will
be able to offer better end-products to end-users that require smaller samples, cost less and give
faster results.
Cascade Microtech's eVue digital imaging system is used for on-wafer test with Cascade
Microtech Probe Stations. It offers enhanced high-definition video, navigation and accuracy for
viewing and profiling a device under test. The eVue allows users to navigate, observe and
measure devices without the need for a conventional microscope. It combines new wafer probe navigation tools with next-generation digital microscope technology and advanced video
processing technologies.
The global trend in Point-of-Care (POC) systems is to increase the functionality of the system by
integrating all of the protocol steps in the process onto one device. This is often referred to as a
lab-on-a-chip and includes the sample preparation, analytical separation and detection steps in
one device, designed as a disposable component that eliminates the time-consuming and labor-
intensive cleaning process that can introduce errors into the process. What follows from this is
the challenge of characterizing the complex, miniaturized microfluidic device to validate and
verify the design. In order to improve the product development process as it currently exists, the
characterization must be accurate, repeatable and reliable.
For engineers and scientists who need to make precision instruments, the probe stations
combined with eVue deliver access to, and extraction of, accurate electrical data from small
structures on wafers, integrated circuits (ICs), IC packages, circuit boards and modules, MEMS,
biological structures and electro-optic devices.
Ecology
Ecological monitoring for which microfluidics is relevant can be found in the military,
civil or commercial use of food, air and water. Due to various technological and product specific
barriers, microfluidics systems have not been widely adopted in these areas. Issues such as large
fluidic volumes, low concentration of samples, and diversity of the substances to be detected
combine to make cost effective commercial products difficult to develop and commercialize.
Additionally, the nature of ecology requires products that range in complexity, density of tests
and autonomy of devices. This makes a standard application for environmental monitoring
difficult to conceive and deliver as the level of distribution and openness of the ecosystem to be
monitored require different levels of complexity of protocol.
The complete integration of sample-in/results-out systems is a long-term goal for
commercialization of microfluidics technology in environmental monitoring, although the
technology for such micro total analytical systems (µTAS) have not yet reached technological
maturity. Therefore, a near-term goal in ecology is to develop a system that performs the
analytical procedures as well as some preparative steps on a microfluidic device or "lab-on-a-
chip." In order to attain this goal, researchers will have to reach a level of efficiency that will
enable them to cost effectively develop and validate lab-on-a-chip devices.

Challenges in the Microfluidics Market
The core problem that researchers in this field experience is that configuring an experiment can
take far too long and is far too complex. Additionally, current methods of experimentation tend
to be destructive and inflexible.
Current methods constrain flexibility in experimentation. In fact, research findings suggest there
are some types of experiments