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   Message 7,865 of 8,931   
   ScienceDaily to All   
   'Fishing' for biomarkers   
   20 Mar 23 22:30:24   
   
   MSGID: 1:317/3 641932ed   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    'Fishing' for biomarkers    
    Researchers have developed a broadly applicable nano-sensor capable of   
   single-molecule precision    
      
     Date:   
         March 20, 2023   
     Source:   
         Syracuse University   
     Summary:   
         Researchers have devised a tiny, nano-sized sensor capable of   
         detecting protein biomarkers in a sample at single-molecule   
         precision. Fittingly coined as 'hook and bait,' a tiny protein   
         binder fuses to a small hole created in the membrane of a cell --   
         known as a nanopore -- which allows ionic solution to flow through   
         it. When the sensor recognizes a targeted molecule, the ionic flow   
         changes. This change in flow serves as the signal from the sensor   
         that the biomarker has been found.   
      
      
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   FULL STORY   
   ==========================================================================   
   While a popular hobby for many, fishing is also a pastime full of   
   uncertainty.   
      
   Each time you have something on the line, you can never be completely sure   
   what type of fish you've hooked until you pull it out of the water. In   
   a similar way, scientists "fishing" for biomarkers -- molecules whose   
   health care applications include signaling for the presence of cancer --   
   in biofluids such as blood can also encounter unpredictability. Finding   
   a specific protein biomarker in a pool of thousands is like trying to   
   catch a particular fish species in the vast ocean.   
      
      
   ==========================================================================   
   Luckily, a team of researchers from Syracuse University's College of Arts   
   and Sciences (A&S), SUNY Upstate Medical University, Ichor Therapeutics,   
   and Clarkson University have devised a tiny, nano-sized sensor   
   capable of detecting protein biomarkers in a sample at single-molecule   
   precision. Fittingly coined as "hook and bait," a tiny protein binder   
   fuses to a small hole created in the membrane of a cell -- known as a   
   nanopore - which allows ionic solution to flow through it. When the   
   sensor recognizes a targeted molecule, the ionic flow changes. This   
   change in flow serves as the signal from the sensor that the biomarker   
   has been found.   
      
   "These nanopores are equipped with hooks that pull certain protein   
   biomarkers from a solution," says Liviu Movileanu, professor of physics   
   in A&S, who co- authored the study along with postdoctoral researcher   
   Mohammad Ahmad. "By fishing them from the solution quickly and accurately,   
   we can better identify and quantify protein biomarkers that are associated   
   with various hematological malignancies and solid tumors."  The team's   
   latest research, published in Nature Communications, addresses previous   
   challenges that existed in making this technology generalizable. Their   
   new findings formulate a sensor design architecture that can be applied   
   to a broad range of protein targets.   
      
   Combining Innovative Technologies For the first time, the team coupled   
   nanopore technology with antibody mimetic technology -- artificially   
   designed protein scaffolds that bind and interact with a specific   
   biomarker and behave like antibodies. Cells inside the body design their   
   own antibodies which bind to and eliminate unwanted substances.   
      
   When it comes to therapeutics, scientists engineer small proteins to   
   penetrate cells and stimulate the production of antibodies which target   
   specific pathogens like viruses or bacteria.   
      
   "Researchers design the scaffolds using established scaffolds from mother   
   nature and adapt them using evolutionary mutagenesis -- where they scan   
   billions of DNA mutations until they find some that interact strongly   
   with a specific protein," says Movileanu, whose work on the project   
   was supported by a $1.2 million grant from the National Institutes   
   of Health. "Creating highly specific protein detection technologies   
   will address these demands and also accelerate discoveries of new   
   biomarkers with potential consequences for the progression of pathological   
   conditions."  According to Movileanu, in addition to working in a clean   
   solution, the sensor is also highly effective in complex biofluids,   
   like blood serum, that contain numerous antibodies.   
      
   "Essentially you have a very specific hook that targets a very specific   
   protein," he explains. "Since the signal encodes the exact protein that   
   you are targeting, this technique does not have false positives, making   
   it practical for biomedical diagnostics."  To validate their findings,   
   the team tested their hypothesis using a blood serum sample. With their   
   technology, they were able to identify and quantify epidermal growth   
   factor receptor (EGFR), a protein biomarker in various cancers. In   
   addition, numerous calibrations of the sensors were conducted using   
   other biophysical techniques.   
      
   At the Forefront of Diagnosis While their paper provides a concept   
   prototype, Movileanu says the project paves the way for broad   
   applications. For example, by integrating the sensors into nanofluidic   
   devices, this technology would allow scientists to test for many   
   different biomarkers at once in a specimen, providing a fundamental   
   basis for biomarker detection in complex biofluids.   
      
   "The future of medicine won't rely as much on imaging and biopsies   
   when diagnosing cancers," says Movileanu. "Instead, researchers will   
   use nano-sensor technology, like what we are developing in our lab, to   
   test blood samples for the presence of various biomarkers associated with   
   different cancers. This research is critical to the future of prognostics,   
   diagnostics and therapeutics."   
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   ==========================================================================   
   Story Source: Materials provided by Syracuse_University. Original written   
   by Dan Bernardi.   
      
   Note: Content may be edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. M. Ahmad, J.-H. Ha, L.A. Mayse, M. Presti, A.J. Wolfe, K.J. Moody,   
      S.   
      
         Loh, L. Movileanu. A Generalizable Nanopore Sensor for Highly   
         Specific Protein Detection at Single-Molecule Precision. Nature   
         Communications, 2023 DOI: 10.1038/s41467-023-36944-9   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/03/230320143814.htm   
      
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