December 29th, 2009 marked the fiftieth anniversary of Richard
Feynman asking the famous question1: Why cannot
we write the entire 24 volumes of the Encyclopedia Brittanica on the head of a
pin? The legendary physicist from Caltech figured that regular type would
need to be shrunk by 1/25,000 to achieve the feat. He offered a $1,000 price for
the first experimental demonstration, which was done in 1985 by Tome Newman, a
grad student from Stanford.
Fifty years post Feynman's lecture, and 25 years after Newman's
demonstration, there is one area where our ability to shrink the physical
embodiment of encoded information to such nanodimensions is proving to be
critical: in barcoding and tagging of individual biomolecules.
Biomolecules – proteins, DNA's, RNAs, lipids, sugars - are the physical
carriers of biological information in every living organism. The ability to
detect and inventorize these molecules is necessary if we are to crack the
algorithms by which biological systems operate, and perhaps more importantly,
they ways in which these algorithms are broken at time of illness.
Deoxyribonucleic Acid (DNA), is the
molecules inside cells that carry genetic information and pass it from one
generation to the next.
Ribonucleic Acid (RNA), is one of two types of nucleic
acid made by cells. RNA contains information that has been copied from DNA (the
other type of nucleic acid). Cells make several different forms of RNA, and each
form has a specific job in the cell. Many forms of RNA have functions related to
making proteins. RNA is also the genetic material of some viruses instead of
DNA. RNA can be made in the laboratory and used in research studies.
Tagging of individual biomolecules with easily detectable nanobarcodes
enables their direct digital counting and quantification. This is a
fundamentally different concept from using functionalized "barcoded" particles
as miniature test tubes, on the surface of which a standard analogue-based
detection assay can be performed. In contrast to such analogue methods, direct
digital counting offers all of the advantages associated with other digital
technologies: accuracy at low cost, sensitivity, and (at least in theory)
infinitely expandable dynamic range.
It was in 2000 in Seattle when I invented the "nanostring",2 a fluorescent nanobarcode for single biomolecules, which
since has resulted in a commercial product3 finding
diverse applications in systems biology. For example, scientists from the Broad
Institute and M.I.T. have used the NanoString barcodes to ask detailed questions
about how our immune system responds to pathogenic challenges4 for it is the detection method that dictates what
nanostructures would need to be synthesized as barcodes.
Using fluorescence labels to encode information in a nanobarcode has multiple
advantages and one substantial limitation: Raleigh's diffraction limit. In 1959
Feynman envisioned that an electron microscope would be used to read-out
information encoded in nanostructures, with resolution exceeding that of optical
detection. Yet, electron microscopy is still an expensive and sophisticated
technique, unsuitable for clinical laboratories and physician's offices.
Dr Krassen Dimitrov and his colleagues at the Single
Molecule Nanotechnology group is now working on new methods for electronic
detection of nanobarcodes, which will offer higher resolution than fluorescence,
yet at very low costs.
2. Methods for detection and quantification of
analytes in complex mixtures. United States Patent 7473767
3. Geiss G.K., Bumgarner R.E., et. al., Direct
multiplexed measurement of gene expression with color-coded probe pairs. Nature
Biotechnology 26, 317 - 325 (2008).
I., Garber M., et. al., Unbiased Reconstruction of a Mammalian Transcriptional
Network Mediating Pathogen Responses. 2009 Oct 9; Vol. 326. no. 5950, pp. 257 -
Copyright AZoNano.com, Dr Krassen Dimitrov (The University of
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