Bioassays
- Related Topics:
- nanomedicine
- grey goo
- nanosensor
- nanowhisker
- nanofabrication
A second area of intense study in nanomedicine is that of developing new diagnostic tools. Motivation for this work ranges from fundamental biomedical research at the level of single genes or cells to point-of-care applications for health delivery services. With advances in molecular biology, much diagnostic work now focuses on detecting specific biological “signatures.” These analyses are referred to as bioassays. Examples include studies to determine which genes are active in response to a particular disease or drug therapy. A general approach involves attaching fluorescing dye molecules to the target biomolecules in order to reveal their concentration.
Another approach to bioassays uses semiconductor nanoparticles, such as cadmium selenide, which emit light of a specific wavelength depending on their size. Different-size particles can be tagged to different receptors so that a wider variety of distinct colour tags are available than can be distinguished for dye molecules. The degradation in fluorescence with repeated excitation for dyes is avoided. Furthermore, various-size particles can be encapsulated in latex beads and their resulting wavelengths read like a bar code. This approach, while still in the exploratory stage, would allow for an enormous number of distinct labels for bioassays.
Another nanotechnology variation on bioassays is to attach one half of the single-stranded complementary DNA segment for the genetic sequence to be detected to one set of gold particles and the other half to a second set of gold particles. When the material of interest is present in a solution, the two attachments cause the gold balls to agglomerate, providing a large change in optical properties that can be seen in the colour of the solution. If both halves of the sequence do not match, no agglomeration will occur and no change will be observed.
Approaches that do not involve optical detection techniques are also being explored with nanoparticles. For example, magnetic nanoparticles can be attached to antibodies that in turn recognize and attach to specific biomolecules. The magnetic particles then act as tags and “handlebars” through which magnetic fields can be used for mixing, extracting, or identifying the attached biomolecules within microlitre- or nanolitre-sized samples. For example, magnetic nanoparticles stay magnetized as a single domain for a significant period, which enables them to be aligned and detected in a magnetic field. In particular, attached antibody–magnetic-nanoparticle combinations rotate slowly and give a distinctive magnetic signal. In contrast, magnetically tagged antibodies that are not attached to the biological material being detected rotate more rapidly and so do not give the same distinctive signal.
Microfluidic systems, or “labs-on-chips,” have been developed for biochemical assays of minuscule samples. Typically cramming numerous electronic and mechanical components into a portable unit no larger than a credit card, they are especially useful for conducting rapid analysis in the field. While these microfluidic systems primarily operate at the microscale (that is, millionths of a metre), nanotechnology has contributed new concepts and will likely play an increasing role in the future. For example, separation of DNA is sensitive to entropic effects, such as the entropy required to unfold DNA of a given length. A new approach to separating DNA could take advantage of its passage through a nanoscale array of posts or channels such that DNA molecules of different lengths would uncoil at different rates.
Other researchers have focused on detecting signal changes as nanometre-wide DNA strands are threaded through a nanoscale pore. Early studies used pores punched in membranes by viruses; artificially fabricated nanopores are also being tested. By applying an electric potential across the membrane in a liquid cell to pull the DNA through, changes in ion current can be measured as different repeating base units of the molecule pass through the pores. Nanotechnology-enabled advances in the entire area of bioassays will clearly impact health care in many ways, from early detection, rapid clinical analysis, and home monitoring to new understanding of molecular biology and genetic-based treatments for fighting disease.
Assistive devices and tissue engineering
Another biomedical application of nanotechnology involves assistive devices for people who have lost or lack certain natural capabilities. For example, researchers hope to design retinal implants for vision-impaired individuals. The concept is to implant chips with photodetector arrays to transmit signals from the retina to the brain via the optic nerve. Meaningful spatial information, even if only at a rudimentary level, would be of great assistance to the blind. Such research illustrates the tremendous challenge of designing hybrid systems that work at the interface between inorganic devices and biological systems.
Closely related research involves implanting nanoscale neural probes in brain tissue to activate and control motor functions. This requires effective and stable “wiring” of many electrodes to neurons. It is exciting because of the possibility of recovery of control for motor-impaired individuals. Studies employing neural stimulation of damaged spinal cords by electrical signals have demonstrated the return of some locomotion. Researchers are also seeking ways to assist in the regeneration and healing of bone, skin, and cartilage—for example, developing synthetic biocompatible or biodegradable structures with nanosized voids that would serve as templates for regenerating specific tissue while delivering chemicals to assist in the repair process. At a more sophisticated level, researchers hope to someday build nanoscale or microscale machines that can repair, assist, or replace more-complex organs.
Information technology
Semiconductor experts agree that the ongoing shrinkage in “conventional” electronic devices will inevitably reach fundamental limits due to quantum effects such as “tunneling,” in which electrons jump out of their prescribed circuit path and create atomic-scale interference between devices. At that point, radical new approaches to data storage and information processing will be required for further advances. For example, radically new systems have been imagined that are based on quantum computing or biomolecular computing.
Molecular electronics
The use of molecules for electronic devices was suggested by Mark Ratner of Northwestern University and Avi Aviram of IBM as early as the 1970s, but proper nanotechnology tools did not become available until the turn of the 21st century. Wiring up molecules some half a nanometre wide and a few nanometres long remains a major challenge, and an understanding of electrical transport through single molecules is only beginning to emerge. A number of groups have been able to demonstrate molecular switches, for example, that could conceivably be used in computer memory or logic arrays. Current areas of research include mechanisms to guide the selection of molecules, architectures for assembling molecules into nanoscale gates, and three-terminal molecules for transistor-like behaviour. More-radical approaches include DNA computing, where single-stranded DNA on a silicon chip would encode all possible variable values and complementary strand interactions would be used for a parallel processing approach to finding solutions. An area related to molecular electronics is that of organic thin-film transistors and light emitters, which promise new applications such as video displays that can be rolled out like wallpaper and flexible electronic newspapers.
Nanotubes and nanowires
Carbon nanotubes have remarkable electronic, mechanical, and chemical properties. Depending on their specific diameter and the bonding arrangement of their carbon atoms, nanotubes exhibit either metallic or semiconducting behaviour. Electrical conduction within a perfect nanotube is ballistic (negligible scattering), with low thermal dissipation. As a result, a wire made from a nanotube, or a nanowire, can carry much more current than an ordinary metal wire of comparable size. At 1.4 nanometres in diameter, nanotubes are about a hundred times smaller than the gate width of silicon semiconductor devices. In addition to nanowires for conduction, transistors, diodes, and simple logic circuits have been demonstrated by combining metallic and semiconductor carbon nanotubes. Similarly, silicon nanowires have been used to build experimental devices, such as field-effect transistors, bipolar transistors, inverters, light-emitting diodes, sensors, and even simple memory. A major challenge for nanowire circuits, as for molecular electronics, is connecting and integrating these devices into a workable high-density architecture. Ideally, the structure would be grown and assembled in place. Crossbar architectures that combine the function of wires and devices are of particular interest.
Single-electron transistors
At nanoscale dimensions the energy required to add one additional electron to a “small island” (isolated physical region)—for example, through a tunneling barrier—becomes significant. This change in energy provides the basis for devising single-electron transistors. At low temperatures, where thermal fluctuations are small, various single-electron-device nanostructures are readily achievable, and extensive research has been carried out for structures with confined electron flow. However, room-temperature applications will require that sizes be reduced significantly, to the one-nanometre range, to achieve stable operation. For large-scale application with millions of devices, as found in current integrated circuits, the need for structures with very uniform size to maintain uniform device characteristics presents a significant challenge. Also, in this and many new nanodevices being explored, the lack of gain is a serious drawback limiting implementation in large-scale electronic circuits.
Spintronics
Spintronics refers to electronic devices that perform logic operations based on not just the electrical charge of carriers but also their spin. For example, information could be transported or stored through the spin-up or spin-down states of electrons. This is a new area of research, and issues include the injection of spin-polarized carriers, their transport, and their detection. The role of nanoscale structure and electronic properties of the ferromagnetic-semiconductor interface on the spin injection process, the growth of new ferromagnetic semiconductors with nanoscale control, and the possible use of nanostructured features to manipulate spin are all of interest.
Information storage
Current approaches to information storage and retrieval include high-density, high-speed, solid-state electronic memories, as well as slower (but generally more spacious) magnetic and optical discs (see computer memory). As the minimum feature size for electronic processing approaches 100 nanometres, nanotechnology provides ways to decrease further the bit size of the stored information, thus increasing density and reducing interconnection distances for obtaining still-higher speeds. For example, the basis of the current generation of magnetic disks is the giant magnetoresistance effect. A magnetic read/write head stores bits of information by setting the direction of the magnetic field in nanometre-thick metallic layers that alternate between ferromagnetic and nonferromagnetic. Differences in spin-dependent scattering of electrons at the interface layers lead to resistance differences that can be read by the magnetic head. Mechanical properties, particularly tribology (friction and wear of moving surfaces), also play an important role in magnetic hard disk drives, since magnetic heads float only about 10 nanometres above spinning magnetic disks.
Another approach to information storage that is dependent on designing nanometre-thick magnetic layers is under commercial development. Known as magnetic random access memory (MRAM), a line of electrically switchable magnetic material is separated from a permanently magnetized layer by a nanoscale nonmagnetic interlayer. A resistance change that depends on the relative alignment of the fields is read electrically from a large array of wires through cross lines. MRAM will require a relatively small evolution from conventional semiconductor manufacturing, and it has the added benefit of producing nonvolatile memory (no power or batteries are needed to maintain stored memory states).
Still at an exploratory stage, studies of electrical conduction through molecules have generated interest in their possible use as memory. While still very speculative, molecular and nanowire approaches to memory are intriguing because of the small volume in which the bits of memory are stored and the effectiveness with which biological systems store large amounts of information.
Communications
Nanoscale structuring of optical devices, such as vertical-cavity surface-emitting lasers (VCSELs), quantum dot lasers, and photonic crystal materials, is leading to additional advances in communications technology.
VCSELs have nanoscale layers of compound semiconductors epitaxially grown into their structure—alternating dielectric layers as mirrors and quantum wells. Quantum wells allow the charge carriers to be confined in well-defined regions and provide the energy conversion into light at desired wavelengths. They are placed in the laser’s cavity to confine carriers at the nodes of a standing wave and to tailor the band structure for more efficient radiative recombination. One-dimensional nanotechnology techniques involving precise growth of very thin epitaxial semiconductor layers were developed during the 1990s. Such nanostructuring has enhanced the efficiency of VCSELs and reduced the current required for lasing to start (called the threshold current). Because of improving performance and their compatibility with planar manufacturing technology, VCSELs are fast becoming a preferred laser source in a variety of communications applications.
More recently, the introduction of quantum dots (regions so small that they can be given a single electric charge) into semiconductor lasers has been investigated and found to give additional benefits—both further reductions in threshold current and narrower line widths. Quantum dots further confine the optical emission modes within a very narrow spectrum and give the lowest threshold current densities for lasing achieved to date in VCSELs. The quantum dots are introduced into the laser during the growth of strained layers, by a process called Stransky-Krastanov growth. They arise because of the lattice mismatch stress and surface tension of the growing film. Improvements in ways to control precisely the resulting quantum dots to a more uniform single size are still being sought.
Photonic crystals provide a new means to control the steering and manipulation of photons based on periodic dielectric lattices with repeat dimensions on the order of the wavelength of light. These materials can have very exotic properties, such as not allowing light within certain wavelengths to be propagated in a material based on the particular periodic structure. Photonic lattices can act as perfect wavelength-selective mirrors to reflect back incident light from all orientations. They provide the basis for optical switching, steering, and wavelength separation on unprecedented small scales. The periodic structures required for these artificial crystals can be configured as both two- and three-dimensional lattices. Optical sources, switches, and routers are being considered, with two-dimensional planar geometries receiving the most attention, because of their greater ease of fabrication.
Another potentially important communications application for nanotechnology is microelectromechanical systems (MEMS), devices sized at the micrometre level (millionths of a metre). MEMS are currently poised to have a major impact on communications via optical switching. In the future, electromechanical devices may shrink to nanodimensions to take advantage of the higher frequencies of mechanical vibration at smaller masses. The natural (resonant) frequency of vibration for small mechanical beams increases as their size decreases, so that little power is needed to drive them as oscillators. Their efficiency is rated by a quality factor, known as Q, which is a ratio of the energy stored per cycle versus the energy dissipated per cycle. The higher the Q, the more precise the absolute frequency of an oscillator. The Q is very high for micro- and nanoscale mechanical oscillators, and these devices can reach very high frequencies (up to microwave frequencies), making them potential low-power replacements for electronic-based oscillators and filters.
Mechanical oscillators have been made from silicon at dimensions of 10 × 100 nanometres, where more than 10 percent of the atoms are less than one atomic distance from the surface. While highly homogeneous materials can be made at these dimensions—for example, single-crystal silicon bars—surfaces play an increasing role at nanoscales, and energy losses increase, presumably because of surface defects and molecular species absorbed on surfaces.
It is possible to envision even higher frequencies, in what might be viewed as the ultimate in nanomechanical systems, by moving from nanomachined structures to molecular systems. As an example, multiwalled carbon nanotubes are being explored for their mechanical properties. When the ends of the outer nanotube are removed, the inner tube may be pulled partway out from the outer tube where van der Waals forces between the two tubes will supply a restoring force. The inner tube can thus oscillate, sliding back and forth inside the outer tube. The resonant frequency of oscillation for such structures is predicted to be above one gigahertz (one billion cycles per second). It is unknown whether connecting such systems to the macro world and protecting them from surface effects will ever be practical.
