New bio-nanometer sensor developed a sharp increase in sensitivity
2018-04-18 23:00:26
[China Instrument Network Instrument Development] For many diseases, the earlier the diagnosis, the better the efficacy and prognosis. Scientists at Imperial College London and Vigo University in Spain have developed a new type of bio-nanosensor that is expected to diagnose diseases earlier.
The signal generated by traditional biosensors is proportional to the concentration of the target molecule. When the concentration of the target molecule is low, the sensitivity of the sensor is reduced and it becomes easy to be disturbed by other molecules.
Contrary to this new sensor developed by Molly Stevens and colleagues, the lower the concentration of the target molecule, the stronger the signal generated, so that a low concentration of target molecules can be reliably detected, and the detectable minimum concentration is lower than that of the hospital. The diagnostic method is several orders of magnitude lower, at least 10 times lower than the most sensitive detection method at present, which is good for early diagnosis of disease. Taking biomarkers such as cancer antigens as an example, the key to early diagnosis is whether it can reliably identify whether the concentration is “zero†or “traceâ€. "For many diseases, using existing technology to find early signs is like finding a needle in a haystack," Stevens said. "And our new technology can really get that needle."
Incubating Nanostars The team created sensors using small Venus (nanostar) diameters of 50 nanometers. The conduction electrons on the gold surface undergo coherent oscillations to form a plasma; glucose oxidase (GOx) adheres to the surface of Venus and acts as a biocatalyst to reduce the silver ions in the solution to silver atoms. When the concentration of GOx is low, silver atoms are deposited around the nanostars, and they are coated with a silver coating, causing the surface plasma resonance frequency to increase (blue shift). When the concentration of GOx is higher, the crystallization rate of silver is also higher, and it is easier to form independent nuclei in the solution, and the resonance frequency shift of the surface plasma of the nanostar is also less obvious. Visible-near-infrared light is emitted to the nanostars, and part of the light will be absorbed. The resonance frequency can be determined by detecting the maximum absorption peak. In this way, as long as the resonance frequency before and after the addition of GOx is measured, the concentration of GOx can be measured very sensitively.
The next task is to use nanosensors to determine the concentration of biomolecules that people are interested in. In this study, scientists determined that the target is a biomarker for prostate cancer called prostate-specific antigen (PSA). To do this, the researchers first packaged Nano Venus with an antibody that scavenges PSA from the solution, then added another antibody that binds to GOx, which in turn binds to the PSA on the nanostar surface; GOx reduces silver ions. The surface plasmon resonance is shifted to be detected.
With this technology, researchers can detect PSA concentrations as low as 10–18 g/ml, which is a billion times lower than the limit that can be detected by a widely used enzyme-linked immunosorbent assay (ELISA) in hospitals.
"The lower the concentration of target molecules, the stronger the signal generated by our sensors," Stevens said. "So even ultra-low concentration target molecules can be detected very reliably."
"Nice trick"
This new technology gave a good impression to David Duffy, head of research at Quanterix Inc. (Quanterix is ​​a company that develops single-molecule protein detection technology in Boston, USA). “It's like a wonderful trick. It's a unique way,†he said. , "It really caught me."
The method of detecting PSA with high sensitivity is very important. After prostate cancer surgery, PSA should no longer appear in the body unless the cancer spreads or the tissue affected by the cancer is not completely removed. “
In the past, people had been unable to detect ultra-low levels of PSA, so PSA is not currently used to judge the effect of surgery. All patients are facing the same risk - they do not know whether the long-term effect of the surgery is successful," Duffy explained. "There is no doubt that this new method is a great step forward in sensitivity compared with the gold standard ELISA. . â€
Looking forward to the future, David Fermin, a nanostructure and electrochemistry expert at the University of Bristol in the United Kingdom, also expressed his appreciation for this new result, calling it "a remarkable job."
Fermin suggested that the next step in the study should focus on the specificity of the assay, ie whether or not a very low concentration of biomarkers can be reliably detected in the presence of potentially interfering substances. “The researchers mentioned this issue simply in the paper, but I think it is very important. I think we can find a clever chemistry method and let this technology become highly specific. It is really exciting,†he said. Say.
So far, researchers have only conducted experiments on PSA, a biomarker, but Stevens said, "We believe this method can be used to diagnose many diseases early." The biomarkers they are interested in also include p24, a protein associated with HIV infection. Accurate detection of p24 will help diagnose the embryonic HIV infection.
(Original title: Nanosensors: A New Star for Early Diagnosis of Disease)
The signal generated by traditional biosensors is proportional to the concentration of the target molecule. When the concentration of the target molecule is low, the sensitivity of the sensor is reduced and it becomes easy to be disturbed by other molecules.
Contrary to this new sensor developed by Molly Stevens and colleagues, the lower the concentration of the target molecule, the stronger the signal generated, so that a low concentration of target molecules can be reliably detected, and the detectable minimum concentration is lower than that of the hospital. The diagnostic method is several orders of magnitude lower, at least 10 times lower than the most sensitive detection method at present, which is good for early diagnosis of disease. Taking biomarkers such as cancer antigens as an example, the key to early diagnosis is whether it can reliably identify whether the concentration is “zero†or “traceâ€. "For many diseases, using existing technology to find early signs is like finding a needle in a haystack," Stevens said. "And our new technology can really get that needle."
Incubating Nanostars The team created sensors using small Venus (nanostar) diameters of 50 nanometers. The conduction electrons on the gold surface undergo coherent oscillations to form a plasma; glucose oxidase (GOx) adheres to the surface of Venus and acts as a biocatalyst to reduce the silver ions in the solution to silver atoms. When the concentration of GOx is low, silver atoms are deposited around the nanostars, and they are coated with a silver coating, causing the surface plasma resonance frequency to increase (blue shift). When the concentration of GOx is higher, the crystallization rate of silver is also higher, and it is easier to form independent nuclei in the solution, and the resonance frequency shift of the surface plasma of the nanostar is also less obvious. Visible-near-infrared light is emitted to the nanostars, and part of the light will be absorbed. The resonance frequency can be determined by detecting the maximum absorption peak. In this way, as long as the resonance frequency before and after the addition of GOx is measured, the concentration of GOx can be measured very sensitively.
The next task is to use nanosensors to determine the concentration of biomolecules that people are interested in. In this study, scientists determined that the target is a biomarker for prostate cancer called prostate-specific antigen (PSA). To do this, the researchers first packaged Nano Venus with an antibody that scavenges PSA from the solution, then added another antibody that binds to GOx, which in turn binds to the PSA on the nanostar surface; GOx reduces silver ions. The surface plasmon resonance is shifted to be detected.
With this technology, researchers can detect PSA concentrations as low as 10–18 g/ml, which is a billion times lower than the limit that can be detected by a widely used enzyme-linked immunosorbent assay (ELISA) in hospitals.
"The lower the concentration of target molecules, the stronger the signal generated by our sensors," Stevens said. "So even ultra-low concentration target molecules can be detected very reliably."
"Nice trick"
This new technology gave a good impression to David Duffy, head of research at Quanterix Inc. (Quanterix is ​​a company that develops single-molecule protein detection technology in Boston, USA). “It's like a wonderful trick. It's a unique way,†he said. , "It really caught me."
The method of detecting PSA with high sensitivity is very important. After prostate cancer surgery, PSA should no longer appear in the body unless the cancer spreads or the tissue affected by the cancer is not completely removed. “
In the past, people had been unable to detect ultra-low levels of PSA, so PSA is not currently used to judge the effect of surgery. All patients are facing the same risk - they do not know whether the long-term effect of the surgery is successful," Duffy explained. "There is no doubt that this new method is a great step forward in sensitivity compared with the gold standard ELISA. . â€
Looking forward to the future, David Fermin, a nanostructure and electrochemistry expert at the University of Bristol in the United Kingdom, also expressed his appreciation for this new result, calling it "a remarkable job."
Fermin suggested that the next step in the study should focus on the specificity of the assay, ie whether or not a very low concentration of biomarkers can be reliably detected in the presence of potentially interfering substances. “The researchers mentioned this issue simply in the paper, but I think it is very important. I think we can find a clever chemistry method and let this technology become highly specific. It is really exciting,†he said. Say.
So far, researchers have only conducted experiments on PSA, a biomarker, but Stevens said, "We believe this method can be used to diagnose many diseases early." The biomarkers they are interested in also include p24, a protein associated with HIV infection. Accurate detection of p24 will help diagnose the embryonic HIV infection.
(Original title: Nanosensors: A New Star for Early Diagnosis of Disease)