Project Name

Primary authors: Andrea Bartlett, Daniel King, Jonghoon Kim, Xiao Ba

Motivation

 Nanotechnology can be applied to detect various molecules inside the body and it is used to diagnose diseases in a shorter amount of time.  It is very important for diseases to be diagnosed at an early stage, especially cancer. According to statistics issued by the National Center for Health Statistics, Centers for Disease Control and Prevention, 2008, the second cause of death in the United States is cancer, killing 559,312 people alone in 2005.

  However, detecting cancer early using nanobiotechnology can eliminate it while it has not matured and may, in turn, decrease the death rate.  For example, pancreatic cancer is very difficult to detect, but using nanotechnology tumor can be discovered more easily and earlier.  Therefore, if we study nanobiotechnology and develop the molecular recognition, then we can increase the amount of people cured from diseases and have a higher quality of life.

Previous work

     There has been quite a bit of research on molecular recoginition as many have recognized the benefits of being able to accurately detect biological signals such as those given by cancerous tumors or infectious diseases. Generally speaking, most species of interest, i.e. cancer cells, do not give off a unique signal that can be detected relatively easily. The process of molecular recoginition involves labeling the species, and only that species, with a molecule that can be detected easily. For most of the previous work, that involves a fluorophore, a luminescent or fluorescent molecule. There are many different types of fluorophore, each giving off a unique wavelength of light. The focus of research on molecular recognition is being able to get the fluorophore attached to a particular species.

Exploiting the vast amounts of antigens and the corresponding antibody has been another area of research on molecular recognition. Because there is only one antibody for a particular antigen, this relationship is very precise. Modification of fragments of antibody so that it can give off a signal can and is done frequently. It is a costly and time consuming process to fragment and properly modify antibodies. Given that there are so many different antibodies, production is on the low scale per antibody and different antibodies are required for different purposes. Thus the main advantage of using antibodies is also the main disadvantage. It is just not economical to use antibodies as a mainstream molecular recoginition method.

Future Strategies

Overview

 Future use of nanotechnology for molecular recognition inside the body has great potential.  Perhaps the biggest goal within the field is being able to place nanoparticles within the body that would essentially be able to monitor the health of the body 24 hours a day, 7 days a week.  This would allow various health risk to be detected almost instantly from inside of the body, in many cases allowing illness to be detected and prevented before symptoms even begin to show, which would obviously be a major step forward from current diagnostic procedures.

Without the use of nanotechnology, the method used to detect different molecules is watching for a binding event by monitoring single colors on fixed arrays.  There are several problems with this current method.  The process is rather slow and very expensive.  Because it monitors through single colors, false positives can result.  Nanotechnology provides a much faster, alternative method of molecular recognition.  Quantum dots, nanorods and nanoprisms are all examples of multicomplex molecular tagging.  This can be applied to identifying different DNA fragments or proteins in the body. 

Quantum Dots 

Quantum dots are more advanced than flourophore tags.  Quantum dots provide wider absorption spectra over which different molecules can be detected.  They are also very useful in molecular recognition because a single wavelength of light can excite a quantum dot to emit multiple colors.  This allows for a vast number of individual signatures (several thousand) which can be used to identify various molecules present in the body.  The colors emitted by quantum dots are visible without the extensive bleachingrequiredfor fluorophore recognition.  Bioconjugated quantum dots have been used to label cells and see the macromolecular level of cells.  Quantum dots are water soluble, and so are easy for the body to break down once they are in the blood stream.  All of these properties of quantum dots give scientists great hope that they can be used in a medical environment in the near future, in particular forlocating tumors within the body.  As of 2005 the major challenges that existed in producing quantum dots (cheifly manufacturability and toxicity when used in living cells) had been overcome.  Quantum dot research is ongoing, and recent research has continued to be very promising.  A report published in December 2008 examined the way that quantum dots could be used as a bioprobe for fast-screening viral agents, and concluded that they did in fact serve as a good detector.  All of this information leads to the conclusion that the future looks bright for quantum dot-related nanotechnology in the field of medicine.

The top image shows Quantum Dot-tagged beads emitting

single-color signals; the bottom image is a display of ten

distinguishable colors emitted by Quantum Dots.

Nanorods  

Nanorods are another facet of nanobiotechnology that could aid in molecular recognition.  They have metal barcoded stripes on them so that they can be detected using their reflective properties.  An optical microscope is used to see the barcodes and identify the molecule.  Nanoprisms are another application of nanotechnology to labeling molecules.  Nanoprisms are made from silver and are used because their shape interacts with light differently than spherical particles, giving a different color than spherical particles.  This enables different nanoparticles to be made of the same material but simply have different shapes, giving them a wider range of colors.  Nanorods are made by placing metal stripes which form barcodes into an aluminum ocide membrane via electro-deposition. 

Nanotubes

Nanotubes are also used in molecular recognition.  These carbon nanotubes have ssDNA probes that react with the target DNA, enabling molecular recognition using an electrochemical method.  Atomic Force Microscopy has also utilized carbon nanotubes as tips.  Atomic Force Microscopy uses high resolution imaging for detecting different DNA fragments.  Like other nanotechnologies, different materials allow different molecules to be detected.

A mass of carbon nanotubes

Living with diabetes can be difficult, not helped by the fact that one must test his/her glucose levels every so often by pricking his/her finger.  This can be quite painful.  Different ways to monitor glucose levels have begun to develop from the fields of nano and micro technologies.  In microtechnology, people have begun to develop patches that can noninvasively monitor glucose by using a biosensor to make small pores (roughly about 50 micrometers in size) that would be undetectable by the patient.  Fluid arises and sensors on the biosensor detect the amount of glucose concentration in the body.  Another way to detect glucose levels is through nanotechnology.  Single-walled carbon nanotubes are implanted into tissue and would react with glucose to give off a fluorescent glow near the infrared region.  The brighter the fluorescent, the higher the concentration of glucose would be.  To see the nanotubes fluoresce, they would be excited simply with a laser pointer.

Nanobiotechnology could greatly change diagnostics.  Specific mutation in DNA could be found through different methods of tagging.

Current Availability

While research has advanced a long way in the past few years, the practical application of nanobiotechnology for molecular detection in humans is still spoken of in hypotheticals.  The field of nanotechnology is so new, relatively speaking, that new research developments seem to occur practially all the time, and as such it is hard to get a real gauge of how close researchers are to perfecting the technology for human use.  Thus, it is almost impossible to come up with a real estimate for the cost of the technology at the moment.  While this may make the practical implementations of nanobiotechnology seem rather up in the air, one gets the impression that this is an area of medicine that we will see a lot of in coming years. 

Citations

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