Biosensors are defined in different ways, but all of the definitions recognize that any biosensor involves a sensor and an analyte or chemical that is determined in an analytical procedure. In blood glucose monitoring, for instance, the analyte reacts with the glucose in the blood. The tenth world congress on biosensors held in Shanghai, China, in May 2008, has defined biosensors as analytical devices incorporating a biological material and either associated with, or integrated within, a physiochemical transducer or transducing microsystem. The transducer may be optical, electrochemical, thermometric, piezoelectric, magnetic, or micromechanical.
For the purpose of this article, we define a biosensor as an analytical device that uses a biological component—a biological or biologically derived material or a biomimic (a synthesized chemical version of a biological substance)—to create a recognition event in the presence of a desired analyte. The biological component is most commonly an enzyme or an antibody.
During the past five years, biosensors have penetrated diverse markets. Research and development institutions, universities, and various industrial sectors have developed, through their research efforts, newer biosensors that can provide highly accurate, sensitive, pain-free diagnostics. These biosensor developments have resulted in increasing adoption of biosensors into the environmental, process industry, security, and biodefense application markets.
In the recent past, R&D investments have focused on miniaturization, which has resulted in smaller, more affordable, and more sensitive test monitors, specifically blood glucose monitors. Although noninvasive biosensing alternatives are emerging, nanotechnology-based biosensors have yet to make a mark.
Approach to Biosensing
Biosensor companies have adopted microchip technology (small semiconductor-based crystal chips embedded with an IC capable of carrying out electronic functions) to reduce the size of their products. To stay ahead of the competition, a number of companies are trying to develop a single platform that can be used for multiple applications. Some of them have been successful in achieving this goal, for example by combining diabetic and cholesterol tests.
Among biosensors, glucose-testing biosensors have the largest market presence. One of the factors for their market leadership is the increasing population of diabetic patients and the rising number of point-of-care applications.
Specialization has helped companies avoid price competition, especially while developing analytes. Although the number of competitors specializing in developing analytes in this space is limited, this trend is gaining ground, especially for protein expression, which relies on the presence or absence of certain compounds that are produced (or not produced) when a protein reacts. Sensors pick up this reaction, analyze it, and then convert the results to a useful diagnostic reading. These are generally analog or digital displays on monitors.
Sensor companies and the biotechnology companies work together while developing the testing device and the target biomolecular strain—a particular variant of a given biomolecule—or analyte. In a number of cases, these biomolecular strains, analytes, or enzymes are sold under the same reseller's brand name under which the biosensor kit is sold. Because the analyte is a consumable, it must work efficiently with the sensor platform to achieve high-precision detection.
Base Biosensor Technologies
Biosensors comprise a combination of at least four systems: a biological or physiological system; an instrumentation or sensing system; and electrical and electronic systems. The biological or physiological system refers to the analyte; the instrumentation or sensing system refers to the instrument, fitted with highly sensitive and accurate sensors; the electrical system refers to the battery and circuitry; and the electronic system manages the conversion to an analog/digital display.
Based on this basic platform, a number of different technologies have been developed to construct biosensors, not all of which are used in the different application types. Figure 1 describes the key biosensor technologies that are currently in use. Electrochemical, piezoelectric, and optoelectronic biosensors have experienced technology improvements, leading to devices based on surface acoustic wave (SAW) or fiber-optic sensing, for example.
Figure 1. The different types of biosensor technologies in use in 2009
In spite of product and technology innovations and improvements, the growth of the biosensors market is still restricted to certain vertical markets. Most biosensors are patented and their market penetration is limited by the resources of the patenting company.
Biosensor awareness and use is limited by a number of factors such as:
- Sensitivity, the most important performance element in a biosensor. Sensitivity in a biosensor refers to real-time detection and measurement of the reaction of the target analyte, and conversion of this measurement into a usable signal.
- Readout times that vary greatly from one biosensor to another. In some biosensors, readout times are very long, in certain cases >20 s.
- The life span of a biomolecule is limited.
- In certain cases, biosensors require a special pre-treatment prior to each use.
- A number of existing sensors lack long-term stability.
- Miniaturization in sensors poses technical challenges.
- Some biosensors are too expensive for commercial production.
- Some biosensors are not sufficiently rugged for their intended applications.
Most of these limitations are inherent in the existing range of devices. However, many of the current designs are achieving readout time, miniaturization, and cost-effectiveness improvements.
Enzyme sensors measure the concentration of a desired chemical substrate by measuring the potentiometric or amperometric response caused by the enzyme-catalyzed reaction between substrate and analyte. Enzyme sensors remain limited to chemistries that allow for a clear signal, such as a change in color, pH (hydrogen ion value), or oxidation state. Use of these enzymes is not suitable for existing biosensor designs.
The biosensors market is categorized as a growth market, with the number of applications increasing as each new biosensor is developed. These developments are gradually leading to standardization of equipment, type of biomolecule, and test processes in the areas of drug discovery, biodefense, environmental monitoring, and narcotic detection.
Biosensors are one of the key interdisciplinary research areas targeted for continuous research and development investments. Innovation in biosensors is an ongoing process and this has ensured its penetration into new markets such as security, military biodefense, environmental monitoring, and the process industry. Other potential target markets are automotive and aerospace.
Silicon microsensors. While the commercialization of silicon-based biosensors has been slow, there has been a gradual increase in the use of microfabrication technologies in the development of new biosensors. This trend is expected to lead to the emergence of new markets. Among existing markets, the promising, high-volume emerging markets include clinical analysis, healthcare, and environmental monitoring.
Fiber-optic biosensors. The use of an optical fiber as a probe or sensing element in biosensors is also gaining ground, due to some of the built-in advantages of optical fibers including excellent light delivery, long interaction length, the ability to capture the emitted light from the targets, and immunity to electrical and magnetic interference. A typical optical biosensor uses absorbance measurements to determine a change in the concentration of analytes that absorb a given wavelength of light. Light is transmitted through an optical fiber to the sample; the amount of light absorbed by the analyte is detected through the same fiber or a second fiber. The biological material is immobilized at the far end of the optical fiber and either produces or extracts the analyte.
The key advantage of optical biosensors is their low cost. We predict that further development of optical-fiber technology will lead to affordable biosensors suited for high-volume production and mass use. Key applications include pharmaceutical drug discovery, clinical applications in point-of-care facilities, industrial, and military and defense.
Fast-detection biosensors. Researchers at Rovira i Virgili University in Tarragona, Spain, recently developed a biosensor that can detect bacteria at levels as low as 1 cell per 5 ml of water, allowing water to be tested for typhoid fever bacteria in only a few seconds. The research used carbon nanotubes containing fragments of DNA (called aptameters) that preferentially bond with Salmonella typhi, the bacteria that causes typhoid fever.
The aptamers—oligonucleic acid or peptide molecules and fragments of DNA or RNA that bond to particular molecules—were secured inside of carbon nanotubes. After being exposed to Salmonella typhi bacteria for a few seconds, the aptamers latch on to the cells, generating a small electrical signal.
Cell-on-chip biosensors. Innovative research work as part of the COCHISE project has resulted in the development of cell-on-chip biosensors to detect cell-to-cell interactions. The focus of this research effort was to identify cells in the immune system that suppress tumor growth. The biosensor is capable of identifying interactions between single cells, detecting signals from biological activity. The COCHISE biosensor uses a combination of microfluidics and electronics to first isolate immune system and cancer cells in a microwell, and then to identify active cells. This may provide a cost-effective tool for the therapeutic monitoring of cancer and is likely to open doors for targeted drug delivery.
Biosensor Approach to Drug Discovery
In 2009, manufacturers of biosensors focused on improving the overall efficiency of the systems used in drug discovery. Large-scale initiatives, such as the human genome project, have generated new approaches to protein detection and genetic analysis for disease detection and offer the expanded use of biosensors in medical applications. The three-pronged strategy to drug discovery includes renewed analysis of the human genome, developing new approaches to detecting proteins, and focusing on genetic analysis for disease detection.
In genetic analysis, biosensors detect the presence of specific genes associated with human diseases. Research efforts include the development of electrochemical, whole-cell, and MEMS-based biosensors. Micro-arrays, based on fluorescence detection techniques, are used in genomics and proteomics research. Due to high cost, they find less usage not only in medical but also in industrial and environmental applications. Innovation based on the detection of differences induced by DNA hybridization on the capacitance of a two-electrode structure and the absorption of UV radiation by a layer of DNA deposited onto top of semiconductor UV sensor have been developed.
Researchers from the National Microelectronics Centre (NMC) are developing a biosensing system to detect mutations of the BRCA1 gene responsible for a virulent form of breast cancer; this could be adapted to detect other genetic deficiencies, proteins linked to viruses, and chemical contamination.
In spite of a number of innovative biosensors developed so far, the biosensors market is still far from meeting some of the key end-user needs. The key unmet needs include:
- development of biosensors capable of multitest detection and monitoring
- development of integrated biosensing platforms
- development of a self-configuring biosensor
- complete multiproduct, multivendor interoperability among biosensors
- migration to lab-on-chip biosensors
- availability of wireless options
The biosensors market is categorized as a growth market with applications increasing with the development of each new biosensor. Biosensor developments have resulted in standardized equipment, standardized biomolecules, and standardized test processes for use in drug discovery, biodefense, environmental monitoring, and the development of an artificial nose for security applications such as narcotics and explosive material detection.
The main vertical markets for biosensors include research laboratories, point-of-care, home diagnostics, process industries, environmental monitoring, security, and biodefense.
The chart in Figure 2 shows that the percent of revenues from markets like environmental, security and biodefense, and home diagnostics have grown from 2006 through 2009 and the forecasts up to 2016 suggest that this growth trend will continue.
Figure 2. The total biosensors market, showing the percent of revenues by vertical markets (world) for 2009 and 2016
Point-of-care continues to be the largest market for biosensors and it is likely to dominate to 2016 and beyond. The development of new biosensor types for new diagnostic tests should contribute to these trends. In biosensors for process applications, we expect a gradual shift from lab tests to inline biosensors to ensure real-time analysis.
Currently, biosensors are used in more than 47 end-user applications (Figure 3), and the number of applications is increasing each year. Although glucose monitoring dominates the market because it is used in both point-of-care and home diagnostics applications, biosensor use in the process industries, environmental monitoring, security, and biodefense is growing in terms of higher adoption within existing applications and development of new biosensor types to cater to specific detection needs.
Figure 3. The total world biosensors market, showing the percent revenues by end-user application for 2009 (Click image for larger version)
The range of end-user applications includes diverse uses such as detecting methamphetamine and opiates in biodefense applications, detecting cardiac biomarkers in point-of-care, and detecting salmonella bacteria in process industries. Continuous large investments are directed toward developing newer biosensors. Instrument manufacturers, meanwhile, cater to the need for higher sensor sensitivity and real-time result outputs. Bioscience companies strive to develop newer biomolecules and newer genetic strains for existing biosensing instruments.
We estimate that the global revenue for the biosensors market will continue to exhibit strong growth and will exceed the $14 billion mark in the next seven years (Figure 4). These revenues are estimated to grow at a CAGR of 11.5% from 2009 to 2016. Annual revenue growth rates are likely to be >12–14% by 2016. The bulk of this growth is from a major increase in demand from the security and biodefense, environmental monitoring, and home diagnostics market segments.
Figure 4. The total biosensors market showing the world revenue forecast for 2009–2016
The home diagnostic market continues to be served through retail, online sales, and manufacturer-direct sales and is likely to exhibit much higher percent revenues over the forecast period. Consequently, its market share is likely to increase during this period. Home diagnostic market revenues are estimated to exhibit growth at a CAGR of 12.4% during the 2009–2016 time period.
Point–of-care will continue to be the largest market until 2016. Biodefense and environmental markets are likely to experience the highest CAGRs, estimated to be in the range of 13%–15% for the period from 2009–2016.
Precision is the most preferred product attribute, and a very important competitive factor. Among end users of biosensors, the largest categories are individuals, patients, and point-of-care institutions; this will remain so over the next seven years.
Research and development in biosensors has resulted in new biosensor types. Numerous promising new types include silicon-based biosensors, use of optical fibers as sensor probes, nanotechnology-based biosensors capable of detecting very low concentrations of bacteria in water, and another biosensor under development for detecting cell-to-cell interactions.
Currently, biosensors are used in more than 47 different end-user applications in contrast to the just over 32 end-user applications seven years ago. Undoubtedly, this growth in end-user applications and expansion into other vertical markets is strongly aided by innovations within the biosensor market; more innovations will occur in the years to come.