Medical Device Link.

Originally Published IVD Technology September 2003

INDUSTRY NEWS

Jennifer Zakroff

Figure 1. The market for nanoscale biosensors is expected to achieve an estimated compound annual growth rate (CAGR) of 92% into 2008 due to nanotechnology in medical diagnostics. Revenue is expected to be generated initially from in vitro applications. Source: Front Line Strategic Consulting Inc. (San Mateo, CA), 2003 (Click to enlarge).

A large effort has been made to advance the field of nanotechnology. Under the Clinton administration, the National Nanotechnology Initiative (www.nano.gov) was put forth. The National Science Technology Council’s Subcommittee on Nanoscale Science (Arlington, VA) offers governmental support for the expansion of this field. Where publicity, funding, and political support lead, the market is likely to follow. IVDs are likely to be at the forefront of this trend. 

According to one study from Front Line Strategic Consulting Inc. (San Mateo, CA), the compound annual growth rate for revenues generated from sales of nanobiosensors is expected to be 92% over the next five years (see Table I). 

A study from Business Communications Company, Inc. (BCC; Norwalk, CT), also forecasts astronomical market growth. This study concludes that the worldwide market for nanoscale devices and molecular modeling will rise at an average annual growth rate (AAGR) of 27.5% from $406 million in 2002 to $1.37 billion in 2007. For revenues derived from biomedical nanoscale devices alone, the study projects a 34.5% AAGR through 2007, at which time it will have become a one-billion-dollar industry. Recent successes in fundamental research support this prediction. 

Engineers at the University of California (UC), Berkeley, have been able to grow silicon nanowires and carbon nanotubes directly on microstructures at room temperature. 

Before this achievement, nanomaterials had to be produced separately and then manually connected to larger systems. The technique of growing the nanotubes and nanowires onto microstructures will eliminate the cumbersome steps involved in connecting them onto microstructures and should speed the commercialization of nanotechnology-based devices. 

A second study at UC Berkeley used a gold rotor on a multiwalled nanotube shaft to develop an electrostatic nanoscale motor that could be used to mix liquids in microfluidic devices. 

Higher-level applications have also been successful. Naomi Halas, professor of chemistry and of electrical and computer engineering, and Jennifer West, associate professor of bioengineering and chemical engineering, at Rice University (Houston) improved upon existing diagnostic platforms by using nanotechnology to produce a fast, inexpensive, and consistent whole-blood immunoassay. The immunoassay is based on a platform that uses nanoshells that are coupled to antibodies and absorb near-infrared light. Near-infrared light penetrates whole blood, so the blood samples need not be processed ahead of time. 

The nanoshells consist of a core of silica or another non-conducting material coated with a gold shell. The nanoshells are conjugated with antibodies, which serve as recognition sites for a specific analyte. The resonance frequency of the nanoshells can be tuned by adjusting the relative dimensions of the silica core and the gold shell. 

As the nanoshells bind to the target molecule, their optical properties change in a characteristic way. By using infrared light to screen for this change in the sample, very low concentrations of antigens can be detected in whole blood with no time-intensive sample preparation. 

The sensitivity of the test is comparable to that of ELISA, although the time required to process the sample is far less: 10 minutes, as compared with several hours. The technology should allow practitioners who work at the point of care to rapidly diagnose stroke, heart attack, and several other diseases. 

The technology has been licensed by Nanospectra Biosciences (Houston), although they are potentially interested in investors and partners. West estimates that the immunoassay should be ready for the market in 2–3 years. “We envision a handheld device where a sample is placed on the device and, a few minutes, later a reading is given. This is so simple and portable that it could be used in the ER, in an ambulance, or by healthcare workers,” says West.

Not only are such advances taking place in academia, but also in national research labs. Scientists at NASA Ames Research Center (Moffett Field, CA) have used carbon nanotubes to develop an ultrasensitive electronic DNA detector. This DNA/RNA microarray platform can be used to directly measure gene expression and detect pathogen presence without polymerase chain reaction (PCR) amplification. 

The chip can detect approximately 300-bp PCR amplicon mRNA, without labeling. The sensitivity can reach less than 1000 targets on each 20 ¥ 20 µm2 electrode. Each electrode consists of approximately 100 vertically aligned carbon nanotubes. 

This level of sensitivity approaches the limit of laser-based fluorescence techniques and is much greater than other electrochemical methods of detection. For detecting DNA, some PCR amplification may be necessary, although the number of cycles will likely be far less than required by conventional electrochemical methods. 

This carbon nanotube nanoelectrode array could be used to detect cancer cells and environmental contaminants. Among the advantages of the chip are that it can be easily interfaced with microelectronics and it uses label-free detection. Since the chip is an electronics-based platform, the assay will be simpler to operate and less expensive to manufacture than other tests. 

The test incorporates a relatively small dynamic signal range. “This technique is very good for detecting very small samples for applications such as early cancer diagnosis. However, it is not ideal for quantitative measurements unless the number of carbon nanotubes is increased, which would then sacrifice the sensitivity,” noted Jun Li, PhD, researcher at the NASA Ames Research Center.

Manufacturers are the key to capitalizing on this technology. “We are currently limited by the fabrication and processing facilities. With the support of manufacturers, development will definitely move much faster. We hope to fill the market’s needs for simple, cheap, and fast diagnostics. A handheld device with disposable cartridges will find applications in point of care, environmental monitoring, homeland defense, and space exploration,” says Li.
Nanotechnology has much in store for the advancement of IVD technology. According to West, “Nanotechnology is a very broad field where many new materials are being developed. A few specific innovations that could impact IVDs include fluorescent materials that are not prone to photobleaching, materials that provide strong surface-enhanced Raman scattering, and nanopatterned surfaces for high-throughput applications.” 

The Front Line study can be found at www.frontlinesmc.com; the BCC study can be found at www.buscom.com.  

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