Method improves single-cell genome analysis - C&EN Global

The transposons tag the DNA fragments so that they get amplified linearly instead of exponentially. The amplified DNA is then used to generate a libra...
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Lanthanide MOFs detect solvents Emissions fingerprinting approach distinguishes among H2O, D2O, and other compounds With the help of a little light, a metal-organic framework (MOF) containing photoluminescent lanthanides can uniquely identify and measure the concentrations of multiple solvents, a research team reports (Chem 2017, DOI: j.chempr.2017.02.010). Applied to a dipstick, the material could enable rapid identification of environ-

um(III). Each lanthanide has a unique emission spectrum: EuIII emits red, GdIII emits ultraviolet, and TbIII emits green light. But when solvent molecules bind within the MOF, the molecules’ vibrational frequencies quench the lanthanide emissions in a way that’s unique to each solvent-lanthanide combination. The researchers

mental contaminants on-site rather than require responders to send samples to a lab. The approach could also solve the tricky analytical problem of determining how much H2O contaminates D2O, an issue for isotopic labeling in biomolecular experiments and calibration for spectroscopic methods such as nuclear magnetic resonance. Led by University of Texas, Austin, chemistry professor Simon M. Humphrey, the team investigated a MOF composed of tris(p-carboxylato)triphenylphosphine and europium(III), gadolinium(III), and terbi-

A triphenylphosphine metal-organic framework containing EuIII and TbIII in a 1:1 ratio emits different colors depending on its solvent exposure. exploited those properties to identify solvents by creating several MOFs with varying ratios of the lanthanides. They exposed each of four MOF varieties to a solvent, excited them at 365 nm, and compared the resulting emission intensity at three wavelengths. The approach allowed the scientists to identify a characteristic fingerprint

for each solvent, thereby distinguishing among H2O, D2O, methanol, ethanol, toluene, benzene, and 12 other solvents. “We were lucky that we stumbled across the right combination of lanthanides to do this,” Humphrey says. He and colleagues created dipstick-like sensors by using spray glue to deposit the MOFs onto glass slides and immersing them in solvents. The researchers could reuse the dipsticks multiple times by heating them to drive off the solvent.

Preliminary data suggest the MOFs also work to selectively detect halogens and heavy metals, Humphrey says. Distinguishing between H2O and D2O is particularly difficult because the two molecules are so similar. “Using a lanthanide MOF as a sensor to detect a trace amount of H2O in D2O is really fantastic work that not only greatly deepens the research of luminescent lanthanide MOFs but also proposes a new application,” comments Peng Chen, a chemistry professor at Nankai University.—JYLLIAN KEMSLEY

GENOMICS

CREDIT: CHEM

Method improves single-cell genome analysis Genomic changes in individual cells can eventually lead to cancer or other diseases. So scientists would like to be able to sequence the genome in a single cell. But the methods to do so can be plagued by the preferential amplification of some regions of the genome over others, leading to incomplete sequence coverage. A team led by X. Sunney Xie of Harvard University and Peking University has developed a whole-genome amplification method that reduces such bias and errors (Science 2017, DOI: 10.1126/science.aak9787). In the method, called LIANTI, research-

ers fragment genomic DNA from a single cell by inserting pieces of DNA called transposons. The transposons tag the DNA fragments so that they get amplified linearly instead of exponentially. The amplified DNA is then used to generate a library for subsequent DNA sequencing. Compared with other whole-genome amplification methods, LIANTI has more uniform amplification and higher sequence coverage. The method enabled the detection of a type of mutation called copy-number variation, which involves the gain or loss of regions of the genome, which is hard to

detect with high resolution using other amplification methods. The researchers were even able to characterize so-called micro-copy-number variations, which are smaller than 100,000 bases, with a resolution of about 10,000 bases. Xie and coworkers used this ability to detect gains and losses of sequences to show that initiation of DNA replication is random and differs from cell to cell. They also showed that many single-nucleotide variations detected in previous single-cell sequencing are artifacts caused by instability of the DNA bases.—CELIA ARNAUD APRIL 17, 2017 | CEN.ACS.ORG | C&EN

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