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Nanoscience Advances in Biology

(Photo Courtesy of University of Toronto, Canada)


- Overview

An important part of modern biology is determining the three-dimensional structure of biological macromolecules such as proteins and nucleic acids and examining the interactions of biomolecular complexes. The methods used to determine the structure of macromolecules, namely X-ray crystallography, nuclear magnetic resonance spectroscopy, mass spectrometry and neutron scattering, have come a long way in the past few years. 

New techniques for mass spectrometry can now provide insight into primary structure and determine precise masses of normal and modified biopolymers. Small-angle neutron scattering (SANS) provides a sophisticated method for evaluating complexes formed between biomolecules and for evaluating conformational changes occurring in solution. In addition, new powerful computational methods could provide a way to predict protein folding and could be valuable in supporting structural data.


- Nanoscience in Biological Science

For biological purposes, nanoscience is an approach that utilizes materials, devices, and systems suitable for use at the nanoscale. Most living mechanisms fall at least partially into this size range. Some examples of natural biological entities measured in the nanometer range are: 

  • The diameter of the DNA double helix is 2 nm
  • The cell membrane is about 10 nm thick
  • Eukaryotic cells are about 10 um in diameter

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


- Microfluidics

Microfluidics is the science of manipulating and controlling fluids, typically in the range of microliters (10-6) to picoliters (10-12), in networks of channels ranging in size from tens to hundreds of micrometers. Microfluidics is a nanoscale technology for manipulating liquids in droplets about 1 picoliter or about 10 microns in diameter. The advantage is that the effective concentration of reagents is increased at these volumes while reducing the diffusion distance. This can improve the efficiency of high-throughput analysis. 

Microfluidics originated in the early 1990s and has grown exponentially. It is seen as an important tool in life science research or in the wider field of biotechnology. Microfluidics is a very attractive technology for both academic researchers and industrial groups because of its size: 

  • Reduce sample and reagent consumption.
  • Shorten the experiment time.
  • Reduce the overall cost of the alliance.

 Furthermore, through miniaturization and automation enabled by microfluidics and nanofluidics, one can: 

  • Improve experimental accuracy
  • Lower detection limit
  • Run multiple analyses simultaneously

Nanoscale materials can be used in clinical diagnostics because their larger surface area can be used to capture biomarkers. The researchers developed a device for analyzing blood using a microfluidic chip with a patterned matrix that uses DNA linkers to bind antibodies. Antibodies detect biomarkers associated with cytokine, growth factor, and antigen expression.


- Micro and Nano-Needles Aid Drug Delivery

Providing treatment in a painless manner is one of many goals in the treatment of clinical conditions. Microneedles and nanoneedles are small devices that can help overcome resistance encountered during drug diffusion by forming small-scale conduits in biofilms. Nanotechnology has been used to develop needles that can deliver substances through cell walls without damaging cells or through human skin, which are less invasive than hypodermic needles. 

In the experiments, patterned silicon nanowire arrays about 50 nm in diameter and 1 um in height were used to deliver molecular agents into cells to promote neuronal growth, siRNA knockdown, and inhibition of apoptosis. They also targeted the protein to the organelle. Another type of nanoneedle array is used to deliver drugs to controlled depths of the skin. Microneedles degrade quickly and leave no traces. 

Microneedles for drug delivery applications were produced manually until the 1990s, and have since been produced using high-precision techniques from the semiconductor industry. Microneedles for transdermal applications have been extensively studied over the past decade or so. Currently, microneedle patches based primarily on hyaluronate are available over the counter for cosmetic applications. 

On the other hand, nanoneedles are used in atomic force microscopy, which have been explored for drug delivery and biosensing over the past two decades. Microneedle- and nanoneedle-based biosensing also brings potential for environment-responsive drug delivery.


- Measurement Devices

Nanoscale pores can be used to separate molecules by size and biochemical properties. Ion channels are an example of a natural structure, rather than distinguishing molecules based on size. Ion channels have selectivity in the angstrom range, or about a tenth of a nanometer. 

The researchers speculate that the same mechanism could be used to unfold and separate DNA to sequence its nucleotides. In one experiment, a modified natural protein pore, alpha-hemolysin, was inserted into a slightly larger synthetic nanopore. Compared with natural pores, mixed pores show higher selectivity and sensitivity, but higher mechanical stability. 

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


[More to come ...]


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