MIT Technology Review has brought to our attention ZS Genetics, a North Reading, MA company that is developing a surprisingly new method of sequencing DNA. Instead of using common bio-chemical methods like PCR, the company is using electron microscopy to effectively image the sequence of DNA molecule’s base pairs. As the company proclaims, they “work at the scale of life.”
More about the technology, taken from the company’s website:
Normal DNA is not visible with electron microscopes (EMs). ZSG has a simple process that makes DNA directly and starkly visible.
Light elements are transparent to Electron Microscopes (EMs). EMs generate contrast from the charges on atomic nuclei. Atoms with low Z are transparent to EMs; atoms with high Z are opaque. The average Z for DNA is around 5.5. The structure of a double strand means that more than half of the cross-section is simply void under EM vacuum conditions, giving an effective average Z of about 2.0. Consequently, natural DNA is essentially invisible to EM analysis.
Normal DNA has only light elements, so it is inherently low contrast. Atomic numbers (Zs) for naturally occurring elements range from 1 to 92. DNA is mostly made of Carbon, Nitrogen, and Oxygen which have Z’s of 6, 7, & 8 respectively. There are also small amounts of Hydrogen and Phosphorus with Z’s of 1 & 15.
ZSG uses heavier elements as labels. Iodated (Z = 53) and Brominated (Z = 35) nucleotides are commercially available. We can use any element, or a combination of elements, with sufficient nuclear charge (Z) to provide an adequate ratio of signal-to-background noise. The specific types of atom(s) we use and the number of base-types labeled depends on the product and application.
Labels of a few or one atom are more precise than fluorescent labels. They are incorporated into the DNA in much the same way as fluorescent labels but are dramatically smaller and consequently easier to incorporate into very long molecules. Atomic label bias should be less than fluorescent labels and also result in greater experiment reproducibility.