Download CLP MicroTechnologies - University of Colorado Boulder

(From the fall 2005 Proof of Concept investment (POCi) proposal by CLP MicroTechnologies)
Development of an ante mortem diagnostic test for Mad Cow disease
Christopher N. Bowman, Dept. of Chemical and Biological Engineering
Kristi S. Anseth, Dept. of Chemical and Biological Engineering
Robert H. Davis, Dept. of Chemical and Biological Engineering
Brian T. Good, CLP MicroTechnologies, Inc.
Project Summary
All of us remember the Mad Cow disease scare in Europe a few years ago. In the U.S., that
memory resurfaced with the discovery of cattle testing positive for Mad Cow disease. This has
ignited fears about the safety of U.S. beef and created concern about the crippling effect another
Mad Cow scare would have on the U.S. beef industry. These limited cases have resulted in a
number of foreign countries banning U.S. beef imports. One example is Japan, who accounted
for almost 40% of U.S. beef exports before the Mad Cow scare [1, 2]. As a result, U.S. beef
prices have dropped and have had a dramatic impact on the $50 billion U.S. beef industry [1].
Part of the fear with Mad Cow disease, scientifically known as bovine spongiform
encephalopathy (BSE), is that it is not well understood. Scientists do know that BSE is a
devastating neurodegenerative disease in cattle caused by misfolded prion proteins that create
holes in the brain of the host. Other prion-related diseases include scrapie in sheep and goats,
chronic wasting disease in deer and elk, and Creutzfeldt-Jakob disease in humans. These
diseases are difficult to detect because the infectious agents are present at very low concentration
levels.
In fact, there is no diagnostic test sensitive enough to determine if live cattle have the
infectious agents that cause BSE. The only reliable test is by post-mortem examination of
brain tissue where infectious agents are at a level that can be detected using current enzymelinked immunosorbent assay (ELISA) tests. However, given the time required to perform the
test, potentially other infected cattle have been slaughtered and entered the food supply
prompting a recall and inciting public fear of beef. If humans eat the tainted beef, they may
become infected with a form of Creutzfeldt-Jakob disease, which has no cure [3].
We will develop a BSE diagnostic device for live cattle by combining three technologies
invented and developed at the University of Colorado. These patented technologies are:
 On Chip Signal Amplification by Photopolymerization,
 Fabrication of 3D Photopolymeric Devices,
 Detection of Molecular Recognition on a Surface-Passivated Microfluidic Device.
CLP MicroTechnologies (CLP) has access to two of these patents through our strategic
partners and the third patent is available for use through the University of Colorado’s
Technology Transfer Office. In combination, this
disruptive technology will provide an early detection
system to enable on-site testing of cattle with rapid,
unambiguous results. The finished device will enable
a veterinarian (or cattle rancher) to simply add the
blood sample into the device and observe the results.
An estimated 200,000 to 300,000 U.S. cattle will Figure 1. Schematic of a possible BSE
be tested in 2005. This number is trending upwards device with inlets for the reagents and blood
sample and a detection area. A positive test
as stricter government regulations are enacted to would result in the formation of a polymer
spot.
2
alleviate domestic and international concern over the U.S. beef supply. For example, Japan is
requesting that all U.S. cattle be tested for BSE. Therefore, the need exists for an easy-to-use,
rapid diagnostic test for the 35 million cattle that are slaughtered each year in the U.S. and 110
million worldwide. In addition, with the ability to test live cattle for BSE, infected cattle can be
removed without contamination concerns.
The United States Dept. of Agriculture, National Institute of Health, and the Dept. of Defense
have identified prion-related diseases as current concerns as evidenced by recent requests for
proposals. We expect our live cattle diagnostic test for BSE (~$10/device) to be cheaper than
current post-mortem ELISA tests (greater than $15/device), with the added benefits of early,
rapid detection, portability and ease of use.
It is important to note that the detection system presented in this proposal is a universal
platform. Our detection system can be adapted for other infection diseases, such as avian flu and
cancer, as well as the detection of biological warfare agents. Once the BSE detection device is
commercialized, CLP will investigate other potential applications.