The complex processes inside living systems emerge from the interactions of countless molecules. Understanding these interactions at the single molecule level is of great importance because mechanisms governing their function can be revealed best by interrogating individual molecules. Scientists rely on single-molecule techniques that allow them to isolate individual molecules and sequentially transport them for measurement and, potentially, manipulation. Most commonly, molecules are interfaced with tools like optical tweezers and atomic force microscopes. These devices are precision force sensors. Many interactions among biological molecules are short lived. Their lifetimes can be as short as a nanosecond. The existing single molecule techniques are limited in their temporal resolution, probing the timescales on the order of several milliseconds to a second. In new work, researchers have extended the reach of single molecule experiments to the microsecond timescale.
In order to get a true picture of the processes and events that take place inside unmodified, living cells, probing techniques need to be non-destructive, noninvasive and in real-time. Due to their small dimensions, high-aspect ratio nanomaterials such as nanofibers, nanowires and carbon nanotubes are ideal for cellular applications since they can cross the cell membrane without causing significant damage. In particular, semiconductor nanowires attract a lot of interest because of their uniformity, reproducibility and possibility of fine-tuning their intrinsic properties - physical dimensions, crystal structure, electrical and optical properties, etc. Researchers have now shown, for the first time, the spontaneous and close interface of arrays of vertically aligned indium arsenide nanowires with two relevant cell lines, human embryonic kidney cells and rat embryonic dorsal root ganglion neurons.
Currently, the most common methods for sizing nanoparticles extract data from bulk measurements. These techniques are inherently averaging and so are unable to effectively resolve mixtures of different-sized particles. While individual nanoparticles can be sized using electron microscopy, this approach is time-consuming and of little utility in assembling significant population statistics. Researchers have now developed a microfluidic device for the all-electronic analysis of complex suspensions of nanoparticles in fluid. This device is capable of detecting and sizing individual and unlabeled particles as small as a few tens of nanometers in diameter at rates estimated to exceed 100,000 particles per second.
Multifunctional nanomaterials have become widely researched in nanomedicine with the goal of developing highly accurate probes for detecting and isolating cancer cells. Of particular interest here are magnetic nanoparticles, which offer the capability of cell isolation from original or enriched samples without the use of centrifugation or filtration. In particular, the combination of fluorescent quantum dots and magnetic nanoparticles into single nanospheres to obtain fluorescent-magnetic bifunctional nanospheres has created the potential for broader applications in biomedicine and in clinical diagnosis. In new work, researchers have now expanded this technique to multiplexed assays. They demonstrated the ability to detect and collect multiple types of cancer cells, such as leukemia cells and prostate cancer cells, from mixed samples within 25 minutes by using a magnet and an ordinary fluorescence microscope.
No matter how precise nanosensors and -probes become, bridging the huge gap between nanoscale dimensions and macroscale structures (e.g., wafer size) has been a tremendous challenge for researchers. Researchers in the U.S. have demonstrated a generalized hybrid nanofabrication concept that combines both top-down (deep-UV lithography) and bottom-up (controlled lateral epitaxial growth and atomic layer deposition) fabrication techniques. This unique methodology allows the development of reproducible nanostructured platforms that contain controlled sub-10 nm gaps between plasmonic nanostructures over an entire wafer, i.e. a 6-12 inch area. This approach opens new horizons to more widespread applications in chemical sensing and biomedical diagnostics.
Research to develop sensors that can rapidly detect biomarkers (associated with certain diseases such as cancer) in whole blood, ideally at the point of care, and when the protein biomarker level in blood is very low (i.e. the disease is in an early stage) is being advanced by nanosensor technology. In a recent development, scientists in Spain have developed a rapid nanochannel-based immunoassay capable of the filtering and subsequent detection of proteins in whole blood without any sample preparation. This is the first time that a simple assay to detect proteins in whole blood using nanochannels has been achieved. This is a simple device and set-up that allows nanochannels to achieve such the double functionality of filtering and detection on the same platform.
A multi-disciplinary research team has introduced a novel label-free optofluidic-nanoplasmonic biosensor and demonstrated direct detection of live viruses from biological media at medically relevant concentrations with little to no sample preparation. This novel platform can be easily adapted for point-of-care diagnostics to detect a broad range of viral pathogens in resource-limited clinical settings at the far corners of the world, in defense and homeland security applications as well as in civilian settings such as airports or other public spaces. This work is the first demonstration of detection of intact viruses using extraordinary light transmission phenomena in plasmonic nanohole arrays.
In order to improve throughput speed of DNA sequencing and reduce its cost, researchers are pursuing real-time solid-state DNA sequencing devices. To that end, electronic functional devices in liquid environments need to be developed, ideally utilizing the compatibility with current complementary metal oxide semiconductor (CMOS) based fabrication technology. In this regard, the combination of electronics and nanofluidics leads to the field of electrofluidics, which utilizes the electrical behaviors of fluids for solid state device applications. In order to explore the ion transport and biomolecule transport through nanochannels, researchers have now reported the fabrication of an electrofluidic platform to study the motion of single molecules, including DNA. The device's nanochannel structures were fabricated with sub-lithographic dimension through top-down based, conventional semiconductor fabrication methods.