Instead of a pan and a pick ax, prospectors of the future might seek gold with a hand-held biosensor that uses a component of DNA to detect traces of the element in water.
The gold sensor is the latest in a series of metal-detecting biosensors under development by Rebecca Lai, an associate professor of chemistry at the University of Nebraska-Lincoln. Other sensors at various stages of development detect mercury, silver or platinum. Similar technology could be used to find cadmium, lead, arsenic, or other metals and metalloids.
A primary purpose for the sensors would be to detect water contaminants, Lai said. She cited the August 2015 blowout of a gold mine near Silverton, Colorado, which spilled chemicals into nearby rivers, as well as the ongoing problems with lead-tainted water supplies in Flint, Michigan.
Fabricated on paper strips about the size of a litmus strip, Lai's sensors are designed to be inexpensive, portable and reusable. Instead of sending water samples away for time-consuming tests, people might someday use the biosensors to routinely monitor household water supplies for lead, mercury, arsenic or other dangerous contaminants.
But Lai also is among scientists searching for new and better ways to find gold. Not only aesthetically appealing and financially valuable, the precious metal is in growing demand for pharmaceutical and scientific purposes, including anti-cancer agents and drugs fighting tuberculosis and rheumatoid arthritis.
"Geochemical exploration for gold is becoming increasingly important to the mining industry," Lai said. "There is a need for developing sensitive, selective and cost-effective analytical methods capable of identifying and quantifying gold in complex biological and environmental samples."
Scientists have employed several strategies to find gold, such as fluorescence-based sensors, nanomaterials and even a whole cell biosensor that uses transgenic E. coli. Lai was a co-author of a 2013 study that explored the use of E. coli as a gold biosensor.
DNA, the carrier of genetic information in nearly all living organisms, might seem an unlikely method to detect gold and other metals. Lai's research, however, exploits long-observed interactions between metal ions and the four basic building blocks of DNA: adenine, cytosine, guanine and thymine.
Different metal ions have affinities with the different DNA bases. The gold sensor, for example, is based on gold ions' interactions with adenine. A mercury sensor is based upon mercury ions' interaction with thymine. A silver sensor would be based upon silver ions' interaction with cytosine.
NUtech Ventures, UNL's affiliate for technology commercialization, is pursuing patent protection and seeking licensing partners for Lai's metal ion sensors. She applied for a patent for the sensors in 2014.
"Although these interactions have been well-studied, they have not been exploited for use in electrochemical metal ion sensing," Lai and doctoral student Yao Wu said in a recent Analytical Chemistry article describing the gold sensor.
Lai and Wu say their article is the first report of how oligoadenines -- short adenine chains -- can be used in the design and fabrication of this class of electrochemical biosensors, which would be able to measure concentrations of a target metal in a water sample as well as its presence.
The DNA-based sensor detects Au(III), a gold ion that originates from the dissolution of metallic gold. The mercury and silver sensors also detect dissolved mercury and silver ions.
"The detected Au(III) has to come from metallic gold, so if gold is found in a water supply, a gold deposit is somewhere nearby," Lai explained.
The DNA-based biosensors need more refinement before they can be made commercially available, she said.
Lai's sensor works by measuring electric current passing from an electrode to a tracer molecule, methylene blue in this case. In the absence of Au(III), the observed current is high because the oligoadenine probes are highly flexible and the electron transfer between the electrode and the tracer molecule is efficient.
But upon binding to Au(III) in the sample, the flexibility of the oligoadenine DNA probes is hindered, resulting in a large reduction in the current from the tracer molecule. The extent of the change in current is used to determine the concentration of AU(III) in the sample.
To allow the sensor to be reused multiple times, the Au(III) is later removed from the sensor with an application of another ligand.
Lai's research focus is on electrochemical ion sensors. Her research has been supported with grants from the National Institutes of Health and the National Science Foundation.
Released on 02/17/2016, at 2:02 AM
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University of Nebraska–Lincoln
Writer: Leslie Reed, University Communications
Diagnostic health care is often restricted in areas with limited resources, because the procedures required to detect many of the molecular markers that can diagnose diseases are too complex or expensive to be used outside of a central laboratory. Researchers in the lab of Rustem Ismagilov, Caltech's Ethel Wilson Bowles and Robert Bowles Professor of Chemistry and Chemical Engineering and director of the Jacobs Institute for Molecular Engineering for Medicine, are inventing new technologies to help bring emerging diagnostic capabilities out of laboratories and to the point of care. Among the important requirements for such diagnostic devices is that the results—or readouts—be robust against a variety of environmental conditions and user errors.
To address the need for a robust readout system for quantitative diagnostics, researchers in the Ismagilov lab have invented a new visual readout method that uses analytical chemistries and image processing to provide unambiguous quantification of single nucleic-acid molecules that can be performed by any cell-phone camera.
The visual readout method is described and validated using RNA from the hepatitis C virus—HCV RNA—in a paper in the February 22 issue of the journal ACS Nano.
The work utilizes a microfluidic technology called SlipChip, which was invented in the Ismagilov lab several years ago. A SlipChip serves as a portable lab-on-a-chip and can be used to quantify concentrations of single molecules. Each SlipChip encodes a complex program for isolating single molecules (such as DNA or RNA) along with chemical reactants in nanoliter-sized wells. The program also controls the complex reactions in each well: the chip consists of two plates that move—or "slip"—relative to one another, with each "slip" joining or separating the hundreds or even thousands of tiny wells, either bringing reactants and molecules into contact or isolating them. The architecture of the chip enables the user to have complete control over these chemical reactions and can prevent contamination, making it an ideal platform for a user-friendly, robust diagnostic device.
The new visual readout method builds upon this SlipChip platform. Special indicator chemistries are integrated into the wells of the SlipChip device. After an amplification reaction—a reaction that multiplies nucleic-acid molecules—wells change color depending on whether the reaction in it was positive or negative. For example, if a SlipChip is being used to count HCV RNA molecules in a sample, a well containing an RNA molecule that amplified during the reaction would turn blue; whereas a well lacking an RNA molecule would remain purple.
To read the result, a user simply takes a picture of the entire SlipChip using any camera phone. Then the photo is processed using a ratiometric approach that transforms the colors detected by the camera's sensor into an unambiguous readout of positives and negatives.
Previous SlipChip technologies utilized a chemical that would fluoresce when a reaction took place within a well. But those readouts can be too subtle for detection by a common cell-phone camera or can require specific lighting conditions. The new method provides guidelines for selecting indicators that yield color changes compatible with the color sensitivities of phone cameras, and the ratiometric processing removes the need for a user to distinguish colors by sight.
"The readout process we developed can be used with any cell-phone camera," says Jesus Rodriguez-Manzano, a postdoctoral scholar in chemical engineering and one of two first authors on the paper. "It is rapid, automated, and doesn't require counting or visual interpretation, so the results can be read by anyone—even users who are color blind or working under poor lighting conditions. This robustness makes our visual readout method appropriate for integration with devices used in any setting, including at the point of care in limited-resource settings. This is critical because the need for highly sensitive diagnostics is greatest in such regions."
The paper is titled "Reading Out Single-Molecule Digital RNA and DNA Isothermal Amplification in Nanoliter Volumes with Unmodified Camera Phones." In addition to Rodriguez-Manzano, Mikhail Karymov is also a first author. Other Caltech coauthors include Stefano Begolo, David Selck, Dmitriy Zhukov, and Erik Jue. The work was funded by grants from the Defense Advanced Research Projects Agency, the National Institutes of Health, and an Innovation in Regulatory Science Award from the Burroughs Wellcome Fund. Microfluidic technologies developed by Ismagilov's group have been licensed to Emerald BioStructures, RainDance Technologies, and SlipChip Corp., of which Ismagilov is a founder.
Written by Lori Dajose
Diatomic hydrogen, H2, is a gas at ordinary pressures (~100 Pa) and temperatures (~300 K, 27 oC). When cooled below 33 K (-240 oC) at pressures greater than 1.3 kPa, H2 liquefies and is used industrially.
In 1935, physicists Eugene Wigner and Hillard Huntington predicted that at sufficiently high pressure (and low enough temperature), hydrogen would become a metallic solid consisting of hydrogen atoms. Jupiter, a giant gas planet, is 90% hydrogen that exists as a diatomic gas in its outer atmosphere. Deeper in, the very large mass of the planet’s atmosphere creates high enough pressure to condense the gaseous H2 into a dense fluid near Jupiter’s surface. Even higher pressures exist in its interior. Computer modeling by planetary scientists suggests that in the interior, pressures near 1.93 x 1011 Pa (193 gigapascals) are sufficient to form liquid metallic hydrogen.
On Earth, laboratories achieve ultra- high pressures by using anvil presses. The target substance is compressed by squeezing it between opposing diamond-tipped metal anvils. Recently, researchers at the University of Edinburgh (Scotland) put a small amount of H2 gas between two diamond anvil presses to create ultra-high pressures as high as 384 gigapascals (55 x 10 6 psi). At a pressure of 325 gigapascal the hydrogen became a solid. It is particularly noteworthy that the process was done at about 300 K, close to room temperature. "This is at much higher pressures and much higher temperatures than previous work”, said researcher Phillip Dalladay-Simpson. This is the first time anyone has seen this form of the hydrogen at such a high temperature. This new phase (form) of hydrogen is called Phase V. To determine the structure of Phase V hydrogen, the researchers fired a laser at it and observed the way the wavelength of the light changed. They found that the hydrogen atoms (not diatomic H2 molecules) form alternating layers of orderly and random arrangements. Further study is needed to more fully characterize Phase V. Doing so at such extreme pressures is not easy. For example, conductivity studies must still be done to validate the possible formation of metallic hydrogen. However, the gap between the anvil diamond tips is so small that electrodes used to test conductivity don’t fit into the gap.
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Instead of a pan and a pick ax, prospectors of the future might seek gold with a hand-held ... Read MoreCounting Molecules with an Ordinary Cell Phone
Diagnostic health care is often restricted in areas with limited resources, because the ... Read MoreA New Hydrogen: Phase V
Diatomic hydrogen, H2, is a gas at ordinary pressures (~100 Pa) and temperatures (~300 ... Read More