Medical Device Link.

Originally Published IVD Technology September 2001

Extraclinical IVD Markets: Growing demand from the ground up

Lon Crosby

Lon Crosby, PhD, is an environmentally aware farmer who heads a technology consulting company (Webster City, IA). He can be reached via e-mail at lon.crosby@starband.net.

To understand this market, several factors must be considered: the impact of site-specific farming technology on crop productivity in terms of quantity and quality, the impact of international ISO 14000 regulations concerning environmental compliance, the impact of Environmental Protection Agency (EPA) regulations, the need to assess plant health in transgenic crops, and the convergence of technology and citizen involvement.

This discussion will focus on the market opportunities related to the use of simple strip assays, because such opportunities in the environmental and agricultural areas are vast. There are other, significant, business opportunities for analytical devices that make use of microsensors and microelectromechanical technologies. For sheer market potential, however, nothing compares with the power of the strip in its various forms.

Building a Better Strip Reader

When read visually, strip assays are at best semiquantitative, because they are based purely upon the visual capabilities and incapabilities of humans. When read electronically, however, those same test strips can produce data that are as good as those produced by automated instruments and often better than those produced by manual analyses involving multiple pipettings or dilutions. Hence, there is a critical need within the IVD marketplace for an automated strip reader that can read many different kinds of strip assays. No user wants to be forced into buying and using a strip reader that can perform only a single strip test.

The specifications for such an automated reader are straightforward. It needs to be a simple yet powerful, universal multicolor strip reader that can routinely read color intensity with 1 bit of 1024 or more accuracy, and handle problems, such as background correction, at the same time. Such a reader could be built around a complementary metal-oxide semiconductor fiber-optic 256-channel diode array spectrometer that can be interfaced to a standard personal data assistant (PDA). Using a PDA means not having to mess with displays, operating systems, and data transfer. The physical interface could be a direct plug-in accessory or universal serial bus connection. Wireless interfaces, on the other hand, would create a future-proof link and a powerful foundation at a reasonable price.

In the agricultural and environmental worlds, location is a critical element, so the system should incorporate a differential global positioning system (GPS) receiver capable of locating it in three-dimensional space to an accuracy of 6 in., as well as a geographic information system (GIS) software package. With a good strip-assay system, an untrained individual can produce better data than most labs, and legal-quality data can be collected by recording the entire test sequence (sampling and analysis) using an interfaced digital video camera such that GPS data (time, date, location) can be simultaneously recorded. This simple reader could also read a bar code printed on each strip to establish traceability and define lot-to-lot variation, read quality control patches to verify the proper handling of strips, and allow the analysis to account for colored background and matrix effects.

How would such a system affect costs? There would be no sample container, no sample collection, and no sample shipment to a lab. The data would be collected on-site in near-real time and verified at the collection site as being correct. There would be no paperwork to fill out, and no report to receive and collate, and the data would already be formatted for transfer to an analytical GIS software package. In one scenario analyzed, labor costs per analysis would be reduced by 95%, if only all of the tests that were needed existed.

Hence, the cost savings are enormous, and the cost of strips could easily be such that common citizens could routinely monitor parameters of interest. For example, a bottle of 50 nitrate/nitrite test strips can be purchased for $15, or 30 cents per strip. By comparison, a local lab charges $12 for a water nitrate/nitrite analysis. With a cost equation such as this, the payback time for a strip-test reader that could interface with an existing PDA or laptop would be amazingly short.

A universal reader would have a significant advantage by enabling multiple assay pads that involve different chemistries and end points to be placed on a single strip. Such a reader could also handle the various colors that are likely to be involved. Moreover, with 256 channels, the reader could use an otherwise blank pad to measure some standard test components, such as chlorophyll and turbidity. Because the movement of the strip would be controlled by a stepper motor, the instrument could read a strip multiple times and calculate reaction rates or movement of a chromatography "front" up a pad. By incorporating a simple thermistor into the reader, the impact of temperature could also be accounted for.

A Team Effort

Looking at cost from a different perspective, citizen involvement in environmental monitoring is rapidly becoming the norm. There are river- and lake-keeper groups, bay watch groups, and ocean monitors. Many states have their own statewide citizen-based volunteer monitoring groups. Since neither scientists nor governments can ever hire enough people to either police the environment or collect enough data to understand it, citizen-based programs are effective because they combine education with monitoring and can provide the comprehensive long-term databases needed to make rational environmental decisions in a timely manner.

To demonstrate this demand, an ad hoc group did an evaluation of how many analyses would be needed to understand the basic environmental issues affecting bodies of water in the state of Iowa. The evaluation accounted for the minimum number of points that would need to be monitored in major bodies and subbodies of water to define an objective reality. At a minimum, it was estimated that information would be needed on nitrate/nitrite, phosphate, turbidity, chlorophyll, Atrazine, pH, and E. coli. The conclusion was that a million sets of analyses would be required—10,000 samples per county per year for a variety of pollutants. If Iowa is typical, the base environmental market is 50 million tests per year across the United States.

In addition to water quality, strip assays can also be used to monitor air quality by doing point measurements. But more interesting is the opportunity to use a sparging system to trap air pollutants on an eight-hour basis and then analyze the collecting fluid. The use of sparging systems is standard industrial hygiene technology from the 1960s and 1970s.

In The Dirt Turning to agriculture, there are 450 million acres of cropland in the United States, 340 million of which are considered "prime." The standard recommendation is that every 4.4 acres of this land should be grid sampled for phosphorus, potassium, and pH every three to five years, and for nitrogen every two years, depending upon crop rotations. This represents a market of 20 million sets of tests per year. However, this recommendation is not followed because the costs of sampling and analysis are prohibitive. The local agribusiness charges $24.20 per grid to sample, test, and print a GIS map of the results.

Research data have shown that 4.4-acre grids are too large and should be reduced to an acre or less if they are to play a critical role in production and environmental protection. Despite such findings, the standard recommendation remains at the larger size purely because of the analytical cost issue. The availability of a good and reasonably priced test system would have an important side effect. It would trigger existing environmental regulations that would mandate this level of testing. In addition, the movement from voluntary to mandatory soil testing would change the entire soil-testing arena.

For example, when animal manure is applied as a plant nutrient source, grid testing for nitrogen, potassium, and phosphorus should be conducted every year to ensure that the manure is not overapplied. Ground water should also be tested for microbial contamination, such as E. coli, and potentially for antibiotics that are fed to animals prophylactically in their feed. In the near future, mandatory testing should also be expected for chemical sources of nutrients, since their potential to pollute is just as great. Nonpoint pollution in large bodies of water, such as Chesapeake Bay and the Gulf of Mexico, will drive these requirements. Over 90% of the prime farmland in the United States falls within these regulated areas.

With mandatory testing, therefore, grid sizes would go down, testing frequency would increase, and the number of tests required would go up. EPA regulations—such as those regulating manure disposal for large animal-feeding operations or proposed regulations to rectify the Gulf of Mexico hypoxia problem—are critical driving forces.

Opportunities Abound

Most people have heard of the ISO 9000 standards for quality, but few have heard of or thought about the impact of ISO 14000 regulations for environmental compliance. In the United States, only a few farms have received ISO 9000 approval, and no farms have applied for ISO 14000 approval. A few U.S. companies are ISO 14000 compliant, with most of them in the automotive and electronics industries where environmental compliance is relatively simple and straightforward. In a nutshell, ISO 14000 ensures that environmental regulations established in the United States will also be followed in Europe and important Asian countries.

Moreover, there is another revolution occurring in agriculture. The technology now exists to take the gene that produces a drug in some natural organisms and insert it into an agricultural crop, thereby turning the plant into a chemical production factory. The industry is projecting that 400 pharmaceuticals— representing 2.4 million U.S. production acres—will be produced in corn and soybeans by 2010. This industry is being driven purely by economics, as the cost of producing a transgenic drug in agricultural crops is 75 to 95% lower than production in a transgenic fermentation system.

Such transgenic production fields are very valuable, so there is an ongoing need to assess plant health. If a problem develops in a cornfield that is growing a transgenic variety genetically engineered to produce a pharmaceutical, it would be important to run a biochemical profile on plant sap to gauge the seriousness of the problem, as well as diagnostic tests to identify the specific problem so it can be treated.

There is one last benefit to developing these alternative markets: it sets the stage for rapid expansion of human IVD opportunities.

Copyright ©2001 IVD Technology