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Nanoscience Advances in Biology

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(Photo Courtesy of University of Toronto, Canada)
 

 

An important component of modern biology is the determination of the three-dimensional structures of large biomolecules such as proteins and nucleic acids and examination of the interaction of biomolecular complexes. The methods that are used for determination of macromolecular structure, namely x-ray crystallography, NMR spectroscopy, mass spectrometry, and neutron scattering, have advanced greatly within the last few years. New techniques in mass spectrometry can now provide insight to primary structure and determination of exact mass of normal and modified biopolymers. Small angle neutron scattering (SANS) provides an exquisite means for evaluating complexes that form between biological molecules and for evaluating conformational changes that occur in solution. Also, new powerful computational methods can provide a means of predicting protein folds and can be valuable in supporting structural data.

For the purposes of biology, nanoscience is an approach that makes use of materials, devices, and systems that are applicable on a nanometer scale. Most of the mechanisms of life fall at least partially into that size range. Some examples of natural biological entities that measure in the nanometer range are:

 

  • the DNA double helix has a 2 nm diameter
  • cell membranes are about 10 nm thick
  • eukaryotic cells have a diameter of about 10 um


Similarly, artificial nanostructures can be constructed at those same dimensions. Some examples of these are nanopores with openings of about 2 nm, nanowires of 10 nm diameter, and nanoparticles of 10 to 100 nanometers in diameter. The chemistry and physics of nanomaterials can unique and surprising, and have led to some important innovations in biological science.

 

- Microfluidics

Microfluidics is the science of manipulating and controlling fluids, usually in the range of microliters (10-6) to picoliters (10-12), in networks of channels with dimensions from tens to hundreds of micrometers. Microfluidics is a nanoscale technology for manipulating liquids in droplets of around 1 picoliter, or about 10 um in diameter. The advantage is that effective concentration of reagents is increased at those volumes, while diffusion distance is decreased. This enables greater efficiency for high throughput assays.

Microfluidics takes its origins in the early 1990’s and has grown exponentially. It is viewed as an essential tool for life science research or in a larger way in biotechnologies. Microfluidics is a very attractive technology for both academic researchers and industrial groups since it considerably:

  • Decreases sample and reagent consumption.
  • Shortens time of experiments.
  • Reduces the overall costs of allications.

 

Furthermore, through the miniaturization and automation made possible by microfluidics and nanofluidics, one may: 

  • Improve the precision of experiments
  • Lower limits of detection
  • Run multiple analyses simultaneously

 

Nanoscale materials are useful in clinical diagnostics because their greater surface area can be used to capture biomarkers. Researchers have developed a device for analysis of blood using microfluidic chips with a patterned matrix that uses DNA linkers to bind antibodies. The antibodies detect biomarkers that correlate with cytokine, growth factor, and antigen expression.

 

- Micro and Nano-Needles Aid Drug Delivery

Delivering therapeutics in a painless manner is one of the many objectives for the treatment of clinical conditions. Micro and nanoneedles are small-scale devices that can help overcome the resistance encountered during drug diffusion by creating conduits of small dimensions through biomembranes. Nanotechnology has been used to develop needles that can deliver substances through cell walls without destroying the cell or through human skin less invasively than a hypodermic needle.

A patterned array of silicon nanowires of about 50 nm in diameter and 1 um in height were used to deliver molecular agents into cells to promote the growth of neurons, siRNA knockdown, and inhibition of apoptosis in experiments. They also targeted proteins to organelles. Another type of nano-needle array was used to deliver drugs to a controlled depth in the skin. The microneedles degrade quickly, leaving no trace. 

Microneedles for drug delivery applications were manually produced until the 1990s and after this the high precision technology from the semiconductor industry was adopted for their production. Over the last decade or so, microneedles for transdermal applications have been widely studied. Currently, microneedle patches, mainly based on hyaluronates, are available over the counter for cosmetic applications. 

On the other hand, nanoneedles are used in atomic force microscopy, which has been explored for drug delivery and biosensing over the last two decades. Micro and nanoneedle-based biosensing also poses potential for environment-responsive drug delivery.

 

- Measurement Devices

Nanoscale pores can be used to separate molecules by size and biochemical properties. Ion channels are one example of a natural structure than discriminate molecules based on size. An ion channel has a selectivity in the angstrom range, or around one tenth of a nanometer. 

Researchers have theorized that the same mechanism can be used to uncoil and separate DNA for sequencing of its nucleotides. In one experiment, a modified natural protein pore, α-hemolysin, was inserted into a somewhat larger synthetic nanopore. The hybrid pore showed an increased selectivity and sensitivity compared to the natural pore, but was more mechanically stable. 

Another measurement device that has been created based on nanotechnology is a carbon nanotube sensor for reactive oxygen species (ROS). It had single-molecule resolution based on optical fluorescence quenching. The sensor was able to identify transient “hot spots” of high ROS concentration near the cell membrane. 

 

 

 

[More to come ...]



 

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