nanotech in biology

Applications of Nanobioengineering:

1. Nanobiosensors and Biochips: To understand biological phenomena and apply them in engineering, it is essential to measure biomolecules that exist in trace amounts. Biological detection technology is crucial not only for initially obtaining large amounts of bioinformation but also for industrial applications like disease prevention and diagnosis. For systems biology research to progress, tools are needed that can compare and analyze large amounts of samples simultaneously. The development of micro bio-analysis systems in the bioindustry is significant for genome and proteome research and new drug development. These systems help reduce costs and improve efficiency in analysis, diagnosis, and drug development. The current trend in bio-analysis systems is miniaturization and the use of arrays to process large sample volumes. Nanotechnology integration is now essential. In most biochip analyses, scanners using laser-induced fluorescence are widely used because binding reactions between DNA and proteins alone cannot generate electrical signals. In this case, samples to be measured are pre-bound with fluorescent substances, which react with biomolecules arranged in an array, and the fluorescence at the binding sites is measured to determine the extent of biochemical reactions. However, this fluorescence detection method requires expensive lasers and is not suitable for ultra-micro array systems. Recently, detection methods using fluorescent semiconductor crystals like water-soluble cadmium selenide have been developed. Fluorescent organic molecules are chemically unstable and require specific lasers to induce fluorescence, but these nanoparticles can be easily excited without lasers, simplifying the measuring equipment and providing high-sensitivity analysis, making them widely applicable. Furthermore, electrical detection methods using nanoparticles, such as the example of maltose-binding proteins, are being developed, where structural changes in specific proteins during biomolecular binding result in electrical detection. For example, disease-related proteins can be detected by coating molecules that bind to proteins on silicon wires with a diameter of 10 nm; when the proteins in the blood adhere to the silicon wires, they cause changes in the wire’s conductivity, allowing the proteins to be detected as electrical signals. Research is also underway on high-sensitivity, miniaturized chemical/biosensors that use single-walled carbon nanotubes (CNTs), which cause changes in resistance due to molecular adsorption on the CNT surface. The greatest advantage of these electrical detection methods is that they are suitable for system integration and miniaturized analytical systems, which makes them a major area of research in nanobiosensor development. Using nanoparticles allows for "solution array" analyses instead of traditional array concepts. This technology is gaining attention as a solution to the challenges of nano-array fabrication. Instead of arranging biomolecules on a two-dimensional surface, beads or nanoparticles are produced and coated with biomolecules bound to fluorescent substances. In this case, by measuring the color of the beads or nanoparticles, it is possible to determine which biomolecule is involved in the reaction, and by measuring the fluorescence on the particle surface, the occurrence and extent of biochemical reactions can be determined. These experiments allow for the simultaneous mixing of nanoparticles coated with biomolecules in the reaction solution, making them advantageous for analyzing large amounts of biosamples.


2. Lab-on-a-Chip and Biofluidic Devices: Microfluidics is a field that researches and develops the foundational and core technologies for micro-total analysis systems (μ-TAS) and the commercialization of lab-on-a-chip technology. μ-TAS refers to a system that integrates multiple experimental steps and reactions, such as chemical and biological experiments and analyses, into a single unit on a lab bench. Such a system can be composed of a sample collection area, microfluidic circuits, detectors, and control units. Lab-on-a-chip, meaning "laboratory on a chip," implements the concept and functionality of μ-TAS on a small chip. To develop a lab-on-a-chip, it is necessary to create microchannels on surfaces of plastic, glass, or silicon that allow fluid to flow, enabling the miniaturization and integration of processes such as sample pretreatment, separation, dilution, mixing, biochemical reactions, and detection on a single chip. So far, development has focused more on biofluidic devices with specific functions rather than lab-on-a-chip systems with integrated functions. In such cases, microfluidics plays an essential role in transporting biofluids. For example, Caliper Technology developed a method for moving fluids using electroosmotic flow generated by applying high voltage across the ends of microchannels. Electrophoresis and electroosmosis, which control fluid flow by applying an electric field of hundreds of volts per centimeter in the direction of the fluid, leverage charge separation at the interface between the fluid and the microchannel. Caliper recently used this electrophoretic separation technique to develop methods for separating DNA, RNA, and proteins by size. However, this method requires multiple electrodes and high-voltage power supplies, which is a limitation. Meanwhile, Micronics has developed a technique that uses molecular diffusion from laminar flow within microfluidic channels, enabling direct blood analysis. This technology has been integrated into microfluidic circuits on plastic cards the size of a credit card, allowing for the separation of red blood cells from plasma and the analysis of enzymes, proteins, electrolytes, and pharmacological substances in plasma. Other biofluidic control techniques being developed include methods using centrifugal force by companies like Tecan and Gyros, and electrowetting methods being researched by UCLA. The multilayer soft lithography technology, commercialized by Caltech's research group and Fluidigm, introduces a design and fabrication method for microfluidic chips capable of parallel analysis by intersecting channels for fluid and air flow in a multilayer structure. This method is expected to be applied to protein crystallization devices, cell lysis for nucleic acid analysis, and other bio-sample parallel preprocessing devices. However, despite the breakthrough in interfacing microfluidic chips, additional external devices are still required for fluid control and reaction measurement within the chips.


3. Bio-inspired Molecular Self-Assembly: The complementary binding of DNA can be applied to the assembly processes of electronic materials through patterning. Although not yet commercialized, attempts are being made to develop molecular wires and liquid crystals using biological materials. For example, coating DNA surfaces with metal results in highly conductive molecular wires, and bacteriophages have been used in liquid crystal production. Using a library of millions of peptides, it is possible to select peptides with selective affinity for semiconductor surfaces, which can be used to create new functional materials. Additionally, carbon nanotubes (CNTs) are a major material for nanodevice research due to their excellent electrical and mechanical properties. However, conventional CNT manufacturing processes require the separation of different types. By utilizing the self-assembly of single-stranded DNA with specific sequences around CNT arrays, the challenging process of CNT separation can be simplified. The electrostatic characteristics of DNA bound to CNTs can be used to distinguish the tube shape, conductivity, and diameter.


4. Intelligent Drug Delivery Systems: Intelligent drug delivery technology can be developed through the convergence of various technologies, such as cell penetration, nanoparticle synthesis, targeting, controlled drug release, gene delivery, and localized drug delivery. This technology is expected to be applied not only to existing drugs but also to future custom-made drugs created through biotechnology. Recently, drug delivery technologies using nanoparticles, selective drug delivery using polymer microchips, and drug delivery systems (DDS) using nanopores with diameters of 10-100 nm have been developed, and several companies are working towards commercialization.


5. Nanomachines, Nano-Bio Devices, and Systems: Molecular motors, such as ATPase hybridized with nanorods, have already been demonstrated. If molecular motors and other nanomachines can eventually be powered by biological energy sources, it may become possible to achieve therapeutic technologies using nanorobots that have been conceptualized for a long time. Recently, German scientists developed a molecular machine using DNA aptamers, which can bind to specific protein molecules like thrombin. DNA aptamers are selective for specific proteins, and their reactions are reversible. This ability to bind and separate allows the aptamers, known as "DNA hands," to assemble molecular-scale machines. Meanwhile, microchips that replace patch-clamps have been commercialized by companies like AVIVA, and nanobio research tools and various nano-bio application technologies, such as biomimetic systems, are expected to advance in the near future.


6. Nanomedicine: Recently, the U.S. NIH developed a roadmap outlining the concept and future development directions for nanomedicine (http://nihroadmap.nih.gov/nanomedicine/). Over the next 10 years, various technologies are expected to develop, including new nanomachines aimed at improving human health, along with advancements in disease diagnosis and treatment. Research is also expected in areas such as molecular imaging using nanoparticles, and treatments involving nanoparticle fluids, as well as studies on cellular biology and biochemistry at the nanoscale level, such as the manipulation of biomolecules like viruses and the interpretation of protein and cellular responses on nanostructures.