Background - University of Massachusetts Lowellfaculty.uml.edu/xwang/16.541/2011/report...

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Commercially Available Biosensors Ben Babineau, Matthew Best, Sean Farrell University of Massachusetts, Lowell Electrical Engineering Department Report 1 Submission 1 March 2011 Abstract There is a great need to create biosensors that are mass- producible. If one were to survey the entire market of biosensors, it would become apparent that it is a market in infancy. There are two major factors within this and similar technology markets: popular demand and the state of the technology. Naturally, those technologies that have market demand will be researched with the most earnestness, while those with less demand may be ignored for a time. However, there are of course many cases where the present technology has not advanced to a stage at which it would be available to the marketplace. Perhaps most notably, cancer detection is in high demand, but currently expensive in-lab equipment must be used. Not only from a marketing standpoint, but even from a humanitarian perspective, it is clear that biosensors should become affordable and

Transcript of Background - University of Massachusetts Lowellfaculty.uml.edu/xwang/16.541/2011/report...

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Commercially Available Biosensors

Ben Babineau, Matthew Best, Sean FarrellUniversity of Massachusetts, LowellElectrical Engineering Department

Report 1 Submission1 March 2011

Abstract

There is a great need to create biosensors that are mass-producible. If one were to survey

the entire market of biosensors, it would become apparent that it is a market in infancy. There are

two major factors within this and similar technology markets: popular demand and the state of

the technology. Naturally, those technologies that have market demand will be researched with

the most earnestness, while those with less demand may be ignored for a time. However, there

are of course many cases where the present technology has not advanced to a stage at which it

would be available to the marketplace. Perhaps most notably, cancer detection is in high demand,

but currently expensive in-lab equipment must be used. Not only from a marketing standpoint,

but even from a humanitarian perspective, it is clear that biosensors should become affordable

and commercially available. This paper will focus on the current status of the biosensor market

and future trends the market may follow. This will be demonstrated through examples of

different biosensors that have been introduced to the market such as home blood glucose

monitors, which have been very successful in the market, and biosensors such as the bodybugg

and Zeo, commercial biosensors which have their own niche market. The different types of

commercially available biosensors will be examined and described according to the industry in

which they exist. Methods of making these biosensors more marketable such as miniaturization

will also be examined.

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Table of Contents

1.0 Background...........................................................................................................................32.0 Why this Project?..................................................................................................................63.0 Commercially Available Biosensors....................................................................................7

3.1 Medical Industry....................................................................................................................73.2 Environmental Industry.........................................................................................................93.3 Food Industry.......................................................................................................................113.4 Niche Market.......................................................................................................................12

4.0 Marketability.......................................................................................................................144.1 The Biosensor Market..........................................................................................................144.2 Techniques for Commercialization......................................................................................174.3 Current Research and Future Trends...................................................................................18

5.0 Current and Future Work....................................................................................................206.0 Resources............................................................................................................................22

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1.0 Background

Biosensors are analytical devices that evaluate biological samples by transduction and

typically utilize the output signal to create a human interface. Biosensors can analyze any

physicochemical substance from a human; it is a general term that may be applied to any device

that senses and transmits information about a biological process from the subject. These devices

are self-contained and are capable of providing specific quantitative or semi-quantitative

analytical information using a biological recognition element which is in direct special contact

with a transduction element. A biosensor is made up of three different elements: the sensitive

biological element, transducer or detector element, and the electronics and signal processor

elements. This sensitive biological element is used to sense the biological material such as

tissue, cell receptors, enzymes, and antibodies. The transducer or detector element works in a

physicochemical manner (optical, electrochemical, etc.) and transforms the signal resulting from

the interaction the sensitive biological element and the biological element into a signal that can

be measured or analyzed by the electronics and signal processing elements. The electronic and

signal processing elements create an output that can be understood by the user.

Though these biosensors are made of the same elements, each set of elements will

operate in a different manner making every biosensor different. One of the main differences

with each biosensor is the method in which the biosensor performs its detection. Within this

broad field, there are of course many methods that scientists and engineers have demonstrated

that may be used to effectively observe a targeted biological process. Many optical biosensors

use photometric detection which is based on the phenomenon of surface plasmon resonance.

This phenomenon uses the excitation of surface plasmons by light. Surface plasmons are surface

electromagnetic waves that propagate in a direction parallel to the metal/dielectric interface.

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These oscillations are very sensitive to any change of its boundary, such as the adsorption of

molecules to the metal surface. The method for detection common in electrochemical biosensors

is based on enzymatic catalysis of a reaction that produces or consumes electrons. The sensor

substrate usually contains three electrodes; a reference, working, and sink electrode. The target

analyte is involved in a reaction that occurs at the active electrode surface, which produces ions

that create a potential. The potential can be measured at a fixed potential or the potential can be

measured at zero current. In another method ion channels are used in a detection method. The

use of an ion channel has been shown to offer sensitive detection of target biological molecules.

This can be done by imbedding the ion channel and attaching it to a gold electrode, which creates

and electrical circuit. Molecules such as antibodies can be bound to the ion channel so that this

molecule controls ion flow through the channel. This creates an electrical conduction, which cis

proportional to the concentration of the target. Piezoelectric sensors use crystals that undergo an

elastic deformation when an electrical potential is applied to them. There are other methods

used, which are more rare, such as thermometric or magnetic detection.

It can be assumed these different methods described above can be used to describe

different types of biosensors. The different types of biosensors can usually be defined by either

the analyte the biosensor is examining or the detection method the biosensor is using. An

enzyme electrode is a type of biosensor where an enzyme is immobilized on the surface of the

electrode, creating a current that can be measured when the enzyme catalyses. An

immunosensor is a biosensor that detects changes in mass that occurs when an antibody binds to

an antigen. A microbial biosensor is a biosensor that couples microrganisms with a transducer

to enable rapid, accurate, and sensitive detection of microbial cells. Another type of biosensor

defined by the analyte is a DNA sensor, which is used for in the detection of DNA. Some of the

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different types of biosensors that use specific detection methods have been described above such

as: electrochemical and optical biosensors. Some other types of biosensors that use different

types of detection methods will now be described. A type of biosensor that is used to detect

surface conductivity or in a more specific case electrolyte conductivity, is an electrical biosensor.

Another type of biosensor is a mass sensitive biosensor which uses frequency adjustment in

piezocrystals or quarts resonators to detect changes in mass of different analytes. A thermal

biosensor can detect changes in temperature and can be used in specific applications such as the

detection in change of skin temperature. The purpose of this paper is to discuss some of these

different types of biosensors and see how they have been commercialized so that they can be

used in a manner that can help an everyday user in applications such as home medical care.

There are many different applications of the described biosensors; however, not all of

these applications can be made into commercial products for everyday use. The different

applications of biosensors can generally be separated by which field or industry will use these

biosensors. The different applications of biosensors can be broken down into categories such as

medical, environmental, food industry, and military applications of biosensors. The largest

application and the historical market driver of commercial biosensors and biosensors in general

is glucose monitoring in diabetes patients. Some other applications of biosensors in the medical

field are detection of pathogens, in-home medical analysis and diagnosis, measurement of

metabolites, insulin therapy, and can even be found in an artificial pancreas as an implantable

glucose sensor. Some environmental applications of biosensors include detection of pesticides

and water contaminants, determining levels of toxic substances before and after bioremediation,

detection of metabolites such as molds, and remote sensing of airborne bacteria. One major use

of biosensors in the food industry is the detection of drug residues, such and antibiotics and

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growth promoters, in food. One military application of biosensors is seen in the use of dip stick

tests. These dip stick tests, which have been looked at by the US Army, are used to detect toxins

such as Q-fever, nerve agents, and yellow rain fungus.

2.0 Why this Project?

In the health field, it is imperative that the maximum amount of people have access to

early warning diagnoses. Aside from conspiracy theories that state that greedy pharmaceutical

companies want us to be sick, the only logical answer to the question of why clinical biosensors

are not widely commercially available is that the state of technology forbids it. While modern

biosensors have been around in some form for many years, there are a number of instances

where the research in the respective field has not yielded a method to create affordable, mass-

marketable versions of the clinical or industrial apparatus. For many researchers, the proof-of-

design prototype is astronomically expensive. Biosensors, as with many technologically

advanced devices, must go through countless design revisions if they are to become viable for

mass production. It requires many researchers to create highly inventive methods in order to

manufacture their designs on a large scale. According to Karlheinz Bock, head of the Polytronic

Systems division of the German bioengineering company Fraunhofer IZM, in reference to an

innovative polymer based biosensor, “This example shows clearly the possibilities for

polytronics. In a networked world, oriented towards people, inexpensive, multifunctional

systems are needed -- for example in Assisted Living. In order to build up the infrastructure

necessary for this, electronic systems have to be produced in large quantities, in a cost-effective

manner on large substrates. And with polymer electronics, this would be perfectly possible…”

(Fraunhofer-Gesellschaft, 1)

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3.0 Commercially Available Biosensors

3.1 Medical Industry

Although it could be stated that the majority of biosensor patents have not been marketed

to consumers, important lessons can be learned from the companies that have ventured out into

the marketplace. By examining and employing the effective methods that have been used to

date, commercial biosensors can become more prolific. While observing the broad, though

admittedly relatively low grossing, spectrum of commercial products on the market, the most

successful by far is the portable glucose meter. Called by economists the historical market driver

of biosensor technology, the glucose meter has been in high demand for many years. These

home blood glucose monitors determine the approximate concentration of glucose in the blood.

These monitors are used by people who suffer from hypoglycemia or diabetes. Typically,

glucose monitors use an electrochemical method to measure the glucose concentration. These

biosensors utilize an enzyme electrode containing glucose oxidizer which reacts with the glucose

in the blood sample. The enzyme is then reoxidized with an excess of mediator reagent and

subsequently the mediator is reoxidized by a reaction at the electrode and a current is created.

The charge passing through the electrode is then indicative of the glucose level in the blood, thus

accurately delivering a message to the human interface (Davis, 1). Due to the high number of

diabetics and hypoglycemic people in developed countries, this product has enjoyed success

from a long list of competitors. Among some of the popular home blood glucose monitors

available in the United States are the FreeStyle Lite, ReliOn, Precision Xtra, and the OneTouch

Ultra. An example of some commercially available home blood glucose monitors can be seen in

Figure 1 which shows the ReliOn series of home blood glucose monitors, which are sold

exclusively at Wal-Mart and Sam’s Club.

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Figure 1. ReliOn series of home blood glucose monitors.

Each product is of very comparable size and has been clinically observed to be of high accuracy.

The technology behind this device has improved leaps and bounds since its conception.

However, even a product as highly developed as this still has room for improvement. Typical

glucose monitors still require the user to prick the finger to draw a blood sample; a process some

find painful. However, companies have proposed the use of fluorescence as an indicator of

glucose concentration, with some clinical evidence. Glucose monitors also have the human-

perpetuated problem of the lack of memory or present-mindedness to check the glucose levels

frequently enough. These devices are inherently slaves to the user and only are effective when

used frequently enough. Some developing products involve implanting a sensor or attaching

comfortable skin-mountable patches that will constantly perform glucose concentration tests,

informing the subject of dangerous glucose levels. Despite the drawbacks of the device, the

glucose monitor is perhaps the strongest example of an effective, inexpensive, mass-produced

biosensor.

The i-STAT Portable Clinical Analyzer is a versatile biosensor that has shown the path

that many medical-based biosensors must take to succeed. This device is a handheld blood

analyzer system with incredible capabilities. This system is made up of disposable cartridge

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which houses the blood sensor and the handheld unit which houses the electronics; a picture of

the system can be seen in Figure 2a (Cartridges) and 2b (Handheld Unit).

Figure 2a. i-STAT disposable blood cartridges

Figure 2b. i-STAT handheld unit.

It provides accurate lab-quality results on the order of minutes. The rapid delivery of results

enables medical professionals to make important situations in any environment (i-STAT, 1).

Though this device is not available on the consumer market, it is a biosensor that has made it

beyond the realm of the industrial and laboratory based market. The technology in devices such

as these must become less expensive so that they will be available on the consumer market. As

such devices can and have saved lives, this medical domain is the one with the highest demand in

the market.

3.2 Environmental Industry

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Though the majority of commercially available biosensors reside in the medical

marketplace, a few outside of that market have been able to be commercialized. In the

agricultural industry, enzyme biosensors, based on the inhibition of cholinesterases, have been

used to detect traces of organophosphates and carbamates from pesticides. One commercially

available biosensor in the agricultural industry, and more specifically for wastewater quality

control, is biological oxygen demand (BOD) analyzers. These BOD analyzers are based on

micro-organisms like the bacteria Rhodococcus erythropolis immobilized in collagen or

polyacrylamide. (Reyes De Corcuera, Cavalieri, 122). An example of a commercially available

BOD analyzer is the inoLab BSB/BOD 740. This laboratory dissolved oxygen meter has been

developed for BODn measurements as described in the “Standard Methods for Examination of

Water and Wastewater”. A picture of the complete BSB/BOD 740 system can be seen in Figure

3.

Figure 3. inoLab BSB/BOD 740 system.

This system allows up to 7 of the users routines for frequently occurring dilution ratios. This

system also allows for the management of up to 540 diluted samples (www.wtw.com). Different

measurements types require different conditions in order for accurate testing to occur. For

example, standard BOD5 measurements, in which the effluent is pretreated and exposed to

bacteria and protozoa, require incubation at 20°C for 5 days. BOD biosensors have throughputs

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of 2 to 20 samples per hour and can measure 0mg/L to 500mg/L BOD (Reyes De Corcuera,

Cavalieri, 122).

Many of the different instrumentations developed for the medical diagnostic market could

be adapted for the environmental market. Though the commercial returns on biosensors created

for the environmental industry are substantially less than that of the medical diagnostics, public

concern and government funding has generated a research effort for applications of biosensors

for the measurement of pollutants and other environmental hazards. Of those biosensors that are

commercially available in the environmental industry, surface plasmon resonance (SPR)

biosensors constitute the most successful type in the commercial market (Rodriguez-Mozaz,

738).

3.3 Food Industry

In an industry such as the food industry, where quality is one of the most important

features, it is very important that sound and accurate inspection occur to ensure food safety is

kept in mind. As such, food must be chemically analyzed to ensure food quality and safety

standards are adhered to. There must be a process in place to ensure that this analysis occurs

between the delivery of raw material to the food-producing company and the delivery of the

produced food to the customer. One commonly used sensor in the analysis of food is enzyme-

based biosensors (Kress-Rogers, 714). Enzyme based biosensors used in food quality control

can be used in the measurement of amino acids, carbohydrates, gases, alcohols, and much more

(Reyes De Corcuera, Cavalieri, 122). Some commercially available biosensors used in the food

industry detect constituents such as sugars, alcohols, and organic acids (Kress-Rogers, 714). The

other few commercially available biosensors in the food industry include antibody-based and

nucleic acid based biosensors, but are used mainly in trial and research laboratories. Though the

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market is driven by medical biosensors, food industry biosensors are expected to yield

substantial returns in the future (Kress-Rogers, 740).

In this particular market, for this particular application of food quality and safety,

problems arise with biosensors that can limit their use or effectiveness. Their implementation in

this particular application is limited by the need of sterility, frequent calibration, and analyte

dilution. Some improvement or further research in these areas could lead to biosensors that

could have more impact in the commercial market. Biosensors that are commercially available

can also be used in specific food industries such as alcohol (wine and beer), yogurt, and soft

drink producers. Immunosensors can be used to ensure food safety by detecting pathogens in

fresh meat, poultry, and fish (Reyes De Corcuera, Cavalieri, 122).

3.4 Niche Market

Another example of a commercially available biosensor is the bodybugg. This product is

an innovative personal calorie management system. A picture of how this particular biosensor is

used can be seen in Figure 4.

Figure 4. The bodybugg in use.

The bodybugg utilizes several physiological sensors to accomplish a high level of integration.

This biosensor uses a heat flux sensor that measures heat dissipation in the body through a

thermally resistant material that interfaces between the skin and the device (bodybugg, 1). The

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bodybugg also measures skin conductivity with their galvanic skin response sensor. In addition,

the skin temperature of the user is measured using a thermistor-based sensor. These biosensors

are combined with the tri-axis microelectromechanical sensor that measures motion to comprise

a highly integrated physical health monitoring system. The different sensors used in the

bodybugg can be seen pictorially in Figure 5.

Figure 5. “Sensor fusion” used in the bodybugg

This product exemplifies the type of biosensor device that demonstrates the non-disease related

marketability of biosensors in general. The bodybugg is a purely consumer-marketed product

and while helpful for physical awareness, is not a device designed for critical health monitoring

or illness prevention. This small but important fact gives hope to the aspiring biosensor

companies hoping to find a niche in the consumer market.

A great example of a commercially available biosensor that utilizes creative new methods

to bring complex in-lab equipment down to the consumer level is the Zeo. The Zeo system can

be seen in Figure 6.

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Figure 6. Zeo system

This device was designed as a sleep analyzer. Improving the user’s sleep by means of educating

them on the factors that lead to bad sleep, this biosensor is thoroughly impressive (My Zeo, 1).

The researchers at Zeo developed a product that is composed of a wireless headband, bedside

display, online analytical tools, and even an email-based personalized coaching program. The

biosensor, located on the center of the headband uses the patent-pending SoftWave sensor to

measure sleep patterns using the electrical signals naturally produced by the human brain. The

name SoftWave comes from the fact that the sensor is similar to a mesh-surface; highly flexible

and very lightweight. As the user sleeps, the Zeo evaluates the quality and quantity of each stage

of sleep throughout the night. This device has been validated to be within a standard deviation of

agreement with the full in-lab polysomnogram more than 80% of the time. This scaled-down,

cost-reduced version of such a powerful test is very much indicative of the level of evolution that

must transpire for many biosensors to become commercially viable.

4.0 Marketability

4.1 The Biosensor Market

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Although there are many different types of biosensors the biosensor market is dominated

by only a few products. For medical diagnostics about ninety percent of all biosensors are

glucose monitors, blood gas monitors, electrolyte analyzers, or metabolite analyzers. These

sensors are used for ordinary people or for medical professionals in the professional office or

hospital settings. These sensors need to be fast, accurate, and reliable as they are used to

measure biological systems which if monitored incorrectly can be disastrous. The majority of

the remaining percentages of biosensors are directed at detecting environmental control,

fermentation monitoring, alcohol testing, food control, and research in laboratories. (Kress-

Rogers, 740)

Glucose monitors were one of the first widely developed and marketed biosensors and

remain the industry driver of the home consumer biosensor market. Because they have such a

large market these sensors are now designed, manufactured, and sold by many different

companies around the world. New advances in technology now allow sensors to be quicker,

more accurate, and easy to use compared to the older technologies they are replacing. The

United States has one of the largest markets for biosensors and glucose meters are projected to

make up to $1.28 billion in sales for the year 2012 (Sean, Resource).

One major thing that drove the biosensor market and more specifically, electrochemical

biosensors used for diabetes monitoring, was the desire for systems that patients could use

themselves while at home. These devices were a significant part of the move forward towards

convenience and ease of use, both of which are necessary for success in the market. The blood

glucose market has shown us some of the necessary hurdles that must be made to obtain success

in this highly risky market. For example, in 1989 Eli Lilly began to market the Direct 30/30, a

reusable biosensor that promised to revolutionize the home glucose monitoring market; however,

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was unsuccessful due to the non-robust user interface. Another issue the home glucose

monitoring market demonstrated was the need for specificity. It is very important for the

biosensor to be able to separate the desired signal from the analyte of interest from other signals

that are present. Another hurdle that must be addressed in order for a biosensor to be successful

in the market is stability. Typically large biological molecules are not stable outside of the

environment for which they were designed. The biosensors must be designed with this in mind

so they can use these biological molecules in tests required to gain useful information. A third

common issue that must be designed around is sensitivity (Kuhn, 26-27).

Though home blood glucose monitors make up the majority of the biosensor market

today, when they were first introduced they were not readily accepted. The initial acceptance of

electrochemical sensors in general was very slow for several reasons. The market for glucose

biosensors, the diabetic population and physicians, was not the same as it is today. Also, the

devices at that time were very primitive and have evolved drastically to be the devices we now

see commercially available. Another major problem was that the manufacturing of the

electrochemical strips proved to be more difficult and expensive than expected. This caused the

market to be dominated by larger market companies which made it very difficult for smaller

players to compete (Kuhn, 27).

Although many countries have a market for biosensors, the United States and Europe

capured 68.73% of the biosensor market in the year 2008. Since the costs to design, fabricate,

and market new biosensors is huge, most companies tend to stick to markets that they know they

can get the most gain. Therefore, sensors that can monitor multiple biological systems or can be

used in a variety of ways allow companies to get the greatest amount of profit from one type of

biosensor.

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4.2 Commercialization Strategy

Commercialization of biosensors has lagged significantly behind the research and

development of biosensors. Although there have been a large number of research projects and

papers as well as patents applying to new devices, the success of biosensors in the research and

development world has not yet translated to success in the commercial world (Lin 99). There are

significant cost and technical barriers that block the commercialization of new sensors. New

products very rarely develop fully before changes in manufacturing processes, automation, and

miniaturization techniques render them obsolete. Therefore, companies spend lots of money on

the research and design side to stay competitive in their field. Successful systems must be able to

be versatile enough and have the ability to support different functions. The ability to support

multiple sensing capabilities allows biosensors to be competitive and to adapt to the changing

demands of the market (Luong 492).

Due to significant upfront costs in research and design and the fact that many of these

designs simply are not successful means that many types of sensors fail and are never successful

on the market if they reach it at all. The demand for biosensors is driven by the needs and wants

of consumers as well as those of the companies that design, fabricate, and market those sensors.

When demand comes directly from the needs or wants of the consumer the demand is call market

pull. But when the demand comes from the companies that are producing the sensors it is called

technology push.

Market pull comes directly from the consumer. Consumers have needs for products like

glucose sensors to monitor monitor their blood sugar levels. Since a large number of people

require a sensor to test their blood everyday it made financial sense for a company to create such

a marketable product. Biosensors have been developed for a wide variety of medical areas for

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personal use (Lin 92). The demand for reliable, quick, and accurate biosensors that can be used

at home instead of in a hospital by a medical professional has developed into the largest area of

development of current biosensors.

Another example of market pull can happen within an area that was already developed as

a direct result of market pull. Personal glucose biosensors were developed as a result of the

consumer need for a way to test glucose levels at home without a medical professional being

present. However, within the glucose biosensor area other pull factors brought about new

features to these sensors. As personal glucose sensors became more common the need for a

sensor that was faster, more accurate, and that required less blood became apparent. Consumers

wanted their glucose monitors to function more accurately whist using less blood. Thus, a pull

from the consumer was created that had to be answered by the designers and manufacturers of

glucose biosensors.

Industrial push takes place when a company or industry attempts to create a market for a

product they are developing. These devices may not represent a true user need as much as a user

want. Devices that reach the market through industrial push are developed in order to create a

new market. These devices often rely on their features as much as their actual purpose in order to

attract a consumer base. Companies hope that their devices will create a need within the

consumer community so that they will be able to develop and see new devices in that market

area.

Due to the fact that these devices are generally not design and manufactured to address a

current consumer need but what the company making them hopes will be come a need, these

devices are often not very successful market contenders. Biosensors that have a definite

consumer need tend to outperform push products due to the fact that there is already a market in

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place for them (Thusu 1). Therefore, these new devices do not need to create their own markets.

This means that creating push biosensors is much riskier than developing ones for an established

market. However, if a company is successful in developing a new market they maintain sole

control of over that market as the sole manufacturer.

4.3 Techniques for Commercialization

The early electrochemical biosensor market, more specifically the home blood glucose

monitoring market, has shown several keys necessary to making competitive biosensors in the

marketplace. Because the biosensor market is a near-commodity market, cost is a major issue.

Not only does the price of the biosensor for the user matter, the cost to manufacture the device is

also very important. In the medical industry, these biosensors may be used to diagnose

potentially life-threatening illnesses; the devices must be of very high quality and accuracy.

Ultimately the end user must be kept in mind when designing the biosensors, so it is crucial to

understand their needs. For example, it might be important to make the biosensor easy to use for

a sight-impaired user group such as the elderly. These sensors must very user-friendly to

encourage frequent testing and better patient care and control. Another issue that this market

demonstrated was the need for the device to easily integrate into the consumer’s life or routine.

In the medical industry many of these sensors are used by physicians and must interface with

their work regime (Kuhn, 27).

Miniaturization also contributes to the reduction of costs in the fabrication of biosensors.

By making the sensors smaller less material can be used, they can be made more electrically

efficient, and the cost for making them can be greatly reduced. This makes the products more

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marketable as people will be more likely to purchase them due to their lower cost (Sean

Reference)

Research in the field of commercial biosensors is done by both universities and

companies. The research generally focuses on the creation of new sensors and the

miniaturization and cost reduction of current sensors. Biosensor research is still a fairly new

field and universities and companies are still learning how to make them as accurate, efficient,

cheap as possible. In one example of academic research, Duke University developed arrays of

tiny electrodes that monitor heart electrical activity. In another research project, 400

individually-addressable microelectrodes were placed on a single 1 cm2 chip which allowed for

special resolution of analyte distribution in small areas (Kuhn, 31). This type of research shows

how miniaturization and microfabrication is being examined and is used as a means to reduce

cost and create a product that is more easily marketable.

4.4 Current Research and Future Trends

In the biosensor market, research and trends are driven by market demands and practices

to make these devices more marketable. Great strives are being made in the home blood glucose

monitoring market to improve this already market leader. With biosensors, especially ones used

in the medical industry, there is always a desire to create biosensors that will provide more

accurate results. Home blood glucose monitors are becoming less invasive and are beginning to

require smaller sample volumes due to an improved reagent to test. The smaller required sample

volume is a good trend for this biosensor, especially for those users who must prick their fingers

several times a day. In order to make these monitors become even less invasive and to push the

envelope, researchers are trying alternative methods to finger pricking. Some researchers are

trying to create implantable glucose sensors that use glucose oxidase immobilized at the surface

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of a reference electrode combination. In another method, a wired enzyme/mediator combination

is stated to reduce oxygen dependencies of the sensor, and provide a reliable result continuously.

In a more difficult approach, some researchers are attempting to create a sensor that can measure

glucose without the use of biological specifiers. Another area of research and development is

making systems more robust for the user (Kuhn, 30-31).

Within the food industry, most research is focused on improving immobilization

techniques of the biological element to increase sensitivity, selectivity, and stability. Stability,

though critical, has received little attention compared to sensitivity and selectivity in part because

of the tendency to design disposable devices used typically in quality assurance laboratories.

The market of biosensors is typically driven by applications necessary in medical diagnosis

rather than use in the agricultural and food industries. One of these trends is miniaturization of

biosensors which is very important in the commercialization of biosensors, which was described

previously in this paper (Reyes De Corcuera, Cavalieri, 122). In order for food industry based

biosensors to have an impact in the market they must be highly specific, rapid, and reliable to be

useful for the complex industry. The high specificity of the biomolecules such as enzymes,

antibodies, or nucleic acids must be kept in mind in order for the detection of one compound in

the presence of a large number of others. Other things that must be kept in mind with biosensors

used in this industry are integrated sample preparation, time reduction for analysis, and cost-

efficient production (Kress-Rogers, 740).

Some work in the field is currently being performed by the Georgia Tech Research

Institute (GTRI) who is testing a new food safety biosensor, which has been developed over the

past four years, that detects pathogens. GTRI is testing their biosensor in a metro Atlanta

processing plant and hope, with positive results, have created a biosensor that will lead to an

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accurate, speedy, and low cost solution to food contamination. This device will be capable of

simultaneously identifying species and determining concentrations of multiple pathogens,

including E. coli and Salmonella in food products in less than two hours while operating on a

processing plant floor. According to Nile Hartman, a biosensor developer and research engineer

at GTRI, the biggest advantage of this biosensor is the “time reduction in assessing the presence

of contamination”. Laboratory tests have proven this biosensor to be very sensitive on the order

of 500 cells per millimeter in minutes, with hopes of future sensitivities of 100 cells per

millimeter. This is a great improvement from current laboratory equipment that has a sensitivity

of 500 cells per millimeter in eight to twenty-four hours at $12,000 to $20,000. These biosensors

will range from $1,000 to $5,000. GTRI believes that if this biosensor performs well in field

tests, which will last up to six months, it can gain market acceptance. (Englehardt)

This biosensor operates with three primary components: integrated optics, immunoassay

techniques, and surface chemistry tests. The biosensor indirectly detects pathogens by

combining immunoassays with a chemical-sensing scheme. In the immunoassay, a series of

antibodies selectively recognize target bacteria. The “capture” antibody captures the target

bacteria and passes it along. The “reporter” antibodies contain enzyme urease, which break

downs down urea that is added and produces ammonia. The chemical sensor detects the

ammonia, which affects the optical properties of the sensor and changes are made in the

transmitted laser light. These changes reveal the presence and concentration of a specific

pathogen (Englehardt).

5.0 Current and Future Work

Team Member Future Work Plans

Ben Babineau Research available commercial biosensors

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Obtain technical information on these biosensors

Matthew Best Marketability of biosensors

Techniques used in industry

Sean Farrell

Availability of biosensors

Miniturization of biosensors

o Techniques and benefits

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6.0 Resources

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Jeffrey D. Newman, Anthony P.F. Turner. “Home Blood Glucose Biosensors: A Commercial Perspective” Biosensors and Bioelectronics, Volume 20, Issue 12, 20th Anniversary of Biosensors and Bioelectronics, 15 June 2005, Pages 2435-2453

Reyes De Corcuera, Jose I., and Cavalieri, Ralph P. "Biosensors." Encyclopedia of Agricultural, Food, and Biological Engineering (2003): 119-23. Print.

Kress-Rogers, Erika. Instrumentation and Sensors for the Food Industry. Ed. Christopher

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Siontorou, CG, and FA Batzias. "Innovation in Biotechnology: Moving from Academic Research

to Product Development--the Case of Biosensors." Department of Industrial Management and

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push versus market pull.” Biotechnology Advances 26.5 (2008) : 492-500.

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Berger, Michael. "Performance Limits of Nanobiosensors." Nanotechnology and Nanoscience |

Nanowerk. Web. 05 Apr. 2011. <http://www.nanowerk.com/spotlight/spotid=666.php>.

"How to Start a Biosensor Company." Startup Business - Innovative Business Ideas - Profitable

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biosensor-company.htm>.

Siontorou, CG, and FA Batzias. "Innovation in Biotechnology: Moving from Academic

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Luong, John H T, Keith B Male, and Jeremy D Glennon. “Biosensor technology: technology

push versus market pull.” Biotechnology Advances 26.5 (2008) : 492-500.

Davis. “Glucose Meters: What’s on the Horizon?” WebMD 20 June 2005. 1 Mar 2011.

<http://diabetes.webmd.com/features/glucose-meters-development>

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<http://www.myzeo.com/pages/4_why_zeo_.cfm>

http://www.biosensors.com/intl/products-technology-critical-care-products

http://www.bodybugg.com/

http://www.myzeo.com/

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http://www.wtw.com/

www.abbottpointofcare.com/

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http://www.sciencedirect.com/

www.rfds.info/pdf/iStatBioSensor.pdf