[HN Gopher] Electrical detection of RNA cancer biomarkers at the...
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       Electrical detection of RNA cancer biomarkers at the single-
       molecule level
        
       Author : jdmark
       Score  : 86 points
       Date   : 2023-08-19 23:29 UTC (23 hours ago)
        
 (HTM) web link (medicalxpress.com)
 (TXT) w3m dump (medicalxpress.com)
        
       | adamredwoods wrote:
       | Prefer: https://www.nature.com/articles/s41598-023-39450-6
       | 
       | Abstract:
       | 
       | >> Cancer is a significant healthcare issue, and early screening
       | methods based on biomarker analysis in liquid biopsies are
       | promising avenues to reduce mortality rates. Electrical detection
       | of nucleic acids at the single molecule level could enable these
       | applications. We examine the electrical detection of RNA cancer
       | biomarkers (KRAS mutants G12C and G12V) as a single-molecule
       | proof-of-concept electrical biosensor for cancer screening
       | applications. We show that the electrical conductance is highly
       | sensitive to the sequence, allowing discrimination of the mutants
       | from a wild-type KRAS sequence differing in just one base. In
       | addition to this high specificity, our results also show that
       | these biosensors are sensitive down to an individual molecule
       | with a high signal-to-noise ratio. These results pave the way for
       | future miniaturized single-molecule electrical biosensors that
       | could be groundbreaking for cancer screening and other
       | applications.
        
       | tux3 wrote:
       | So, they seem to have made special DNA probes that attaches to
       | some cancer-specific bit of RNA, and the combination of the two
       | stuck together is something they can detect via "scanning
       | tunneling microscopy break junction (STM-BJ)". Is that right?
       | 
       | I guess the question is whether you can use this DNA/RNA
       | detection method _without_ having a whole sophisticated STM setup
       | as the other part of the detector. The article says calls it a
       | nanobiosensor, and says it  "has a promising future as an
       | inexpensive, highly sensitive and label-free miniaturized device
       | for early-stage cancer screening of liquid biopsies".
       | 
       | This is really cool, but it's only a nanobiosensor insomuch as
       | you can get a useful signal out of it without an expensive
       | scanning tunneling microscope setup attached, I would assume!
        
         | haldujai wrote:
         | Basically. It's been a while since I've worked in wetlabs
         | (clinical now) but looking at their methodology the fixed
         | equipment costs would seem comparable to ddPCR and I'd expect
         | cheaper than NGS currently used for ctDNA. Per-unit consumable
         | costs also seem negligible.
         | 
         | The specific AFM setup they used here is pretty old and can be
         | replicated (relatively) inexpensively.
         | 
         | I would guess the biggest cost barrier/disadvantage would be
         | throughput rather than setup costs but these results appear to
         | be a potentially good and/or cost-effective solution to the
         | sensitivity issues.
        
         | camus_absurd wrote:
         | I think you're overestimating the complexity of an stm setup.
         | There exist small coffee machine sized stm machines because the
         | principal behind the operation is relatively straightforward.
         | People have made diy stm machines using piezo electric buzzers
         | as the component that moves a tungsten needle over a sample.
         | It's relatively easy to make atomically thick tungsten needle
         | points because of how it fractures along its grain structure.
         | The tech behind the principle of operation of an stm is already
         | ubiquitous.
        
       | arrosenberg wrote:
       | This is neat, but seems wildly more complex than other detection
       | methods with liquid biopsy. Most major players in this space are
       | using methylation analysis with high specificity and sensitivity
       | - it's not obvious to me that there is a benefit to electrical
       | detection over that.
        
         | haldujai wrote:
         | Not sure I follow, methylation analysis is very different from
         | NA detection.
        
       | cancer-research wrote:
       | Apologies for my enthusiastic interruption. I am deeply intrigued
       | by this ctDNA work using electrical signal detection. However, I
       | see two challenges with current early detection liquid biopsy
       | methods. Firstly, they target signals that are inherently rare in
       | blood (less than 1% of any blood volume). Secondly, they focus on
       | either cfDNA or ctDNA, indicating that cancer has already
       | progressed significantly or spread to other areas.
       | 
       | In this context, I strongly believe that our approach positions
       | us as one of the most captivating players in this field. We aim
       | to leverage the immune response as an indicator of the body's
       | cancer status. By harnessing the highly effective detectors
       | within the immune system, we actively pursue cancer detection.
       | Additionally, relying solely on specific biomarkers seems
       | reminiscent of manually curating features, akin to the early days
       | of NLP when compared to modern transformers.
       | 
       | We are eager to share some of our methodologies and eagerly seek
       | collaboration with professionals from diverse backgrounds,
       | including genomics, wet lab scientists, bioinformatics experts,
       | as well as AI and full stack engineers. Although we are currently
       | in stealth mode and cannot divulge extensive details, we would be
       | thrilled to engage with inquisitive and enthusiastic scientists.
       | In some ways, we believe that our approach may also enable us to
       | validate the efforts of the prominent players in the field of
       | multi-cancer early detection.
       | 
       | For further discussions, please feel free to reach us at
       | qubind@qubind.com.
        
       | car wrote:
       | Why is this getting so many upvotes? Pretty unspectacular stuff.
        
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       (page generated 2023-08-20 23:00 UTC)