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Originally Published January 2000

E-nose technologies promise new diagnostic instruments

Researchers expand interest in developing new applications for artificial olfactory-sensor devices.

Dean S. Skelley

In many industries, odors can be a warning sign of potential problems. If a specific odor is present, it can help diagnose a medical condition, indicate that a food product is spoiled, or detect odors from failing electronic components.

While the human nose can detect and distinguish literally thousands of odors, it is much more practical (and pleasant) to let an instrument do the job. Electronic-nose devices are available to perform these functions, but they are inconvenient and not always accurate. They are larger than most desktop computers and can be hindered by such variables as temperature and humidity. Companies in the electronic-nose technology business are racing to develop smaller and more-precise devices as the number of possible applications grows ever larger.

Graphical representation of a polymer composite sensor; the yellow line indicates flow of current through the carbon particles embedded in the insulating polymer matrix.

Companies concerned about monitoring the quality of their products or the environment in which they are manufactured are scrambling to find ways to use the technology to cut costs and improve their profits. Medical-research scientists are also turning to these new devices to explore diagnostic capabilities unthinkable several years ago. Chemical engineers are rapidly teaming up with researchers in other fields to develop other applications for this emerging technology.

How the Nose Works

The human nose contains about one million receptors for smell. Upon stimulation by smells or odors in the air, olfactory receptors lining the nose send signals to the brain's olfactory bulb. The brain then organizes these signals into patterns that enable the person to detect, identify, and remember distinct odors.

Electronic noses work similarly. At Cyrano Sciences (Pasadena, CA), researchers have developed handheld detectors that resemble mobile phones—devices that can act much like a real nose. They are able to not only detect smells and odors, but also to identify what they are.

The Cyranose 320 detector contains a chip made up of 32 sensors. The sensors are composed of conducting particles evenly dispersed in a polymer matrix. Vapors that interact with these composite particles cause the polymers to expand, much like a sponge, increasing the resistance of the composite. A change in resistance generates a distinct response signal similar to the signal sent to the human olfactory bulb. An electrical signal pattern, or fingerprint, is generated by the sensor array.

The fingerprint pattern derived from the sensor array is used to determine the type, quantity, or quality of the odor being sensed or detected. The pattern can be seen visually, while connection ports on the battery-operated device enable data to be downloaded into spreadsheets. Data can be retrieved later or compared with patterns of known or standard aromas. After registering a pattern distinctive of the vapor or odor analyzed in the air, the detector can be purged and quickly used again. Detectors can sense multiple odors and can be operated in almost any environment without special sample preparation or isolation conditions.

The electronic-nose device can test air samples for concentration levels. The pattern of resistance changes within the array identifies the particular vapor affecting the detector and creates a unique pattern for each one analyzed. The amplitude of the pattern indicates the concentration of the test sample.

Medical Applications

The electronic-nose device may provide physicians with a quicker and more accurate diagnostic tool for a number of diseases. Current interest focuses on the detection and identification of certain chemical compounds in exhaled air and excreted urine or body fluids related to specific metabolic conditions, certain skin diseases, or bacterial infections.

Scientists at Cranfield University (Cranfield, Bedfordshire, UK) are taking a different approach to diagnosing urinary tract infections. In a device called the Diag-Nose, they mix a patient's bacterially infected urine with a special growth medium that contains specially formulated compounds. Upon ingestion by the contaminating bacteria the compounds will release characteristic odors that can be detected by a sensor device, leading to a quick diagnosis and earlier treatment of the patient.

Identifying the responsible bacterial organism usually takes up to two days—the method developed at Cranfield takes five to six hours. Initial clinical trials look very promising, according to a university spokesperson, and a much larger multicenter trial, involving thousands of patients, will commence soon. Other conditions that scientists are looking to diagnose include tuberculosis, gastric conditions such as ulcers, and cancers that could be potentially diagnosed through the breath, such as esophageal or lung cancer.

Representation of the sensor after exposure to a vapor, where the sensor has swollen and the conducting pathway (yellow line) has been altered.

Researchers in the Dental School at the University of California, Los Angeles, are evaluating the potential of Cyrano's device for quantitatively measuring the vapors emitted from bacteria known to be sources of oral malodor (bad breath). The identification of specific odor-emitting bacteria could provide a method for treating oral problems which, left untreated, could lead to major problems affecting the gums or teeth. Odor-emitting Helicobacter pylori, a bacterium found to be responsible for intestinal ulcers, can also be detected and identified. Samples of urine contaminated with certain kinds of bacteria may also be tested in a rapid, cost-effective manner. Some researchers feel that the electronic nose will be helpful in monitoring patients with liver cirrhosis, as well as those with melanomas.

Other potential medical applications arise from the observation that some animals can detect wounds, skin lesions, or tumor growths by smell.

The electronic nose may also provide more-accurate, real-time patient monitoring during anesthesia administration. Cyrano is also conducting clinical trials with its device at Children's Hospital Los Angeles to investigate early detection and diagnosis of upper-respiratory infections.

Electronic-nose detectors may also find use as an adjunct in monitoring diabetic or prediabetic patients, automobile drivers or drug abusers for alcohol or drug ingestion, or by animal breeders to evaluate times of estrus.

Process Control in the Food Industry

Another area being developed as a potential application for electronic-nose technology is as a quality control monitor in the food-processing industry. Cyrano claims its device will be able to check for spoilage, contamination, freshness, and batch-to-batch consistency in foods and beverages.

Applications in the food-processing industry could enable large companies and restaurants to spot-test for immediate results or to monitor continually for spoilage. The detector picks up odors or smells elaborated by the bacteria on produce that is spoiled or rotting. The technology could also have benefits in home use. Such devices may one day be built into refrigerators or microwave ovens.

Off-odors are one of the main reasons customers reject food products. These odors can originate within the food item itself, in the environment surrounding the food in storage or transit, or from the packaging material designed to protect food quality. Odor transfer becomes an unacceptable problem when it passes to other products, especially those with a high fat content, such as chocolate or potato chips. The detectors can clearly show which food samples are good or unacceptable based on the different pattern produced by the sensor array.

A Cyranose chip with 32 proprietary composite polymer sensors.

The present method for assessing odor transfer, the Robinson test, requires food to be placed in close proximity to the packaging material and the aroma and taste evaluated after a 40-hour exposure. The electronic nose detector can detect off-odors much more quickly based on the different patterns produced by the sensor array.

In one experiment, Cyrano Sciences studied the discrimination of essential oils of flavors and fragrances that provide the unique character of spices, fruits, and flowers. Blends of these oils can be classified and treated as discrete formulations, with sensor technology simplifying the classification by using the aroma signature of the essential oil as an objective description. The detectors are not only able to discriminate between the two mint flavors, spearmint and peppermint, but are also able to distinguish between the sources of two spearmint samples, demonstrating a high power of resolution.

Electronic-nose detectors can also be used to classify various coffee aromas into major classes, with further subgroupings of the aromas made by focusing the analysis on each individual class.

Chemical and Environmental Advances

Chemical industries should be able to use these handheld detectors to easily pinpoint the locations of odors. Because current leak detection and monitoring techniques are resource intensive and cumbersome, leading chemical companies are presently evaluating the technology for use in the development of products to detect leaks in pipelines and storage containers.

Opportunities for electronic-nose technology applications are creating much interest in the areas of environmental surveillance. Toxic spills could be identified, as well as levels of air pollution. Spotting explosives and counterfeit drugs or products could be made easier. The detectors may also provide in-line quality control and quality assessment in industrial, packaging, automotive, and petrochemical processing. Initial studies have shown these devices to be valuable as an aid in solvent verification and in the determination of chemical additives for the automotive market.

Other chemical uses being studied are in the fields of cosmetics and electronics production. Marconi Technologies (Chelmsford, Essex, UK) has expanded its business from using electronic sniffers to detect gas leaks to new ventures such as testing the quality of propylene glycol in lotions, and the ammonia levels in frozen shrimp, which can indicate freshness. AromaScan, (Crewe, Cheshire, UK) has 200 of its electronic noses operating around the world. One of the company's instruments was reportedly installed on the Mir space station to detect odors from failing electronic components.

Governmental agencies will also be able to profile a chemical environment in a hazardous materials situation, enabling emergency crews to accurately select a fire retardant, containment strategies, and protective gear.

Cyrano's electronic nose: How it works

The first patent for Cyrano's proprietary electronic nose sensor technology was granted in the mid-1990s. Since then, the company has applied for and received numerous patents for improvements in this area.

Although the technology is not yet perfected for use in the IVD industry, sensors respond very well to vapors produced as a by-product of bacterial breakdown. A diagnosis can be made in less time than with traditional methods. The company has recently signed an agreement with Welch Allyn to create diagnostic products that use its odor-sensor technology.

Meanwhile, the company's first commercial product, the Cyranose 320, will hit the market in March 2000. It will be used in the food and beverage industry as a screening tool for consistency in packaging and raw materials.

The nose's technology works similarly to the way a human smells odors. In the artificial nose, different sensors, each composed of a unique polymer and conducting material, are mounted on an electronic chip. The polymer sensors are wired through microelectronic circuitry to an electrical detector that can record changes in their conductivity.

The process by which the sample is measured follows. First, the sensors are purged, then a sample is drawn in with the instrument's pump and passed over the 32 sensors. Each polymer reacts to chemicals in the air (e.g., aromas, smells, or odors) by differentially absorbing the chemicals. This leads to the composite expanding in size, much like a sponge expands when directly exposed to a liquid. The increased size in the polymeric material, due to its absorption of the specifically reacting material, changes the electrical resistance read by the detector.

A sensory array, consisting of 32 different polymeric composites, will respond to a gaseous chemical as a collective group to generate a different profile of electrical resistances or a set of signals. The collective array of these 32 different resistances creates a unique pattern of electrical signals or a fingerprint, which is reproducible when exposed to the same chemical stimuli. The detector can be standardized against known gaseous chemicals by storing the various fingerprints of electrical signals of known chemicals. Furthermore, the amplitude of the signal can be used to determine the amount of the unknown substance being detected.

The company says marketing a diagnostic product is still three to five years down the road. Issues have to be resolved in terms of what kinds of samples to take (e.g., breath, urine vapor, or sweat), and the challenges related to differing baselines. There are also regulatory hurdles to jump.

Other challenges for the future include increasing the number of polymers in the instrument, which will increase sensitivity. The company's long-term goal is to manufacture a nose chip with thousands of sensors for use in consumer applications from medical diagnostic breathalyzers to smart room air monitors to appliances that are able to detect food preparedness and spoilage.



New Ventures

The potential for these and other applications in the emerging electronic-nose industry has prompted collaborative relationships with technological development groups. In January 1999, Hewlett-Packard (HP; Palo Alto, CA) and Cyrano agreed to work together to develop Cyrano's proprietary sensor technology into products for a variety of markets.

HP's marketing manager Jeff White points out that while the HP4440A chemical sensor is targeted at quality assurance and quality control laboratories, HP recognizes "the need to have products that can address broader applications. Cyrano's approach—to develop portable, inexpensive, and easy-to-use products for nonlaboratory industrial uses and beyond—complements ours. We believe their chip-based sensors will find applications in many different markets, including the large and exciting home market."

Cyrano has also entered into a licensing agreement with Welch Allyn Inc. (Skaneateles Falls, NY) to create medical diagnostic products incorporating Cyrano's proprietary sensor technology. The company plans to launch its handheld device in March 2000 for use in the food-safety field. They will not submit an application for FDA approval for medical diagnostic use for at least a year.

Conclusion

A whole new generation of artificial noses offers a powerful and easy-to-use smell identification system. Recent advances with low power requirements allow for battery-operated, handheld devices that are more user-friendly than currently marketed products.

The development of electronic-nose technology and its applications has generated tremendous interest in countless fields. The devices may become just as ubiquitous as the mobile phones they resemble.

The drive to still-greater miniaturization and lower cost will lead to chip-based products suitable for high-volume, low-cost consumer-oriented markets.

Dean S. Skelley is president of Technical & Professional Services Inc. (San Antonio, TX).

Illustrations courtesy Cyrano Sciences



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