[HN Gopher] Launch HN: Volta Labs (YC W19) - Easier sample prep ...
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       Launch HN: Volta Labs (YC W19) - Easier sample prep for genomics
        
       Hi HN, I'm Udayan Umapathi, founder of Volta Labs
       (https://www.voltalabs.com), a genomics applications company that
       is using advanced electrowetting technology to solve one of the
       toughest challenges facing the genomics industry--scalable sample
       prep. We've built a walk-away benchtop sample prep system that
       comes preloaded with apps that require no user programming or
       optimization, enabling labs to maximize resources, scale sample
       throughput, and reduce risks related to manual handling. I filmed a
       quick video in the lab if you want to see what it looks like IRL:
       https://vimeo.com/935960826/d0efdf3f14.  Sample prep is the process
       of going from raw biological samples to sequenceable molecules. The
       process typically involves isolating nucleic acids from samples
       like blood/cells, breaking up these nucleic acids into small
       pieces, and adding barcodes at a molecular level.  Although
       sequencing technologies have made huge advancements in general,
       sample preparation is largely still done manually and remains a
       bottleneck. Many companies, small and large, have attempted to
       develop solutions that haven't panned out. A couple things make it
       so challenging:  (1) The number of sample types - for humans alone,
       sample types include blood, saliva, various tissue types, buccal
       swab, etc. Each has its own requirements when it comes to handling
       to isolate nucleic acids, and even within each type there are
       significant differences. For example, blood from various donors has
       different cell density.  (2) There is a large array of chemistries
       for different analyses and sequencing technologies, and there is a
       need for flexibility in throughputs to process a few samples at a
       time or run large batches.  Developing a technology that is
       flexible enough to work with various sample types and chemistries
       while maintaining quality spans many disciplines: fluidic dynamics,
       thermal engineering, molecular biology, material science,
       mechanical engineering, electrical engineering, and software
       engineering.  I didn't set out to develop a way to automate sample
       prep. I was exploring the use of electrowetting to manipulate
       colored droplets on a circuit board during my research in the MIT
       Media Lab. During one of my demos, there was huge interest from
       biologists at the lab as well as from biotech/pharma sponsors. I
       quickly began to realize that the application of this technology
       and the potential impact it could have was much larger than I had
       anticipated. I immediately got to work studying biology, focusing
       on five broad markets that included DNA sequencing and synthetic
       biology. The opportunity in the well-established DNA sequencing
       market begging for a solution to improve the quality of samples,
       reduce costs and create throughput flexibility led me to developing
       a way to automate sample prep. And here we are today, bringing it
       to market.  The Callisto Sample Prep System is a sequencer-agnostic
       benchtop system that enables a push-button, walkaway sample prep
       experience. This enables all labs--labs already using sequencing
       automation, and those new to sequencing--to free up resources and
       not rely on skilled labor to maximize throughput. By automating the
       process end to end, reliably, scientists can focus on other aspects
       of research and development.  What exactly does the instrument do?
       It manipulates little droplets on a surface using electric and
       magnetic fields. These droplets contain DNA, RNA, enzymes and other
       biochemistries, or they can be raw samples such as blood, saliva,
       etc. Once these droplets are on the surface, we move, merge, mix
       and split them in various ways. We also incubate these samples to
       specific temperatures on the same surface. We also use traditional
       robotic technologies such as gantry and pipettors for a limited set
       of operations.  Our approach has many advantages over existing
       technologies: it allows us to reduce total cost to our customers
       with less plastic waste and reagent usage; it improves quality of
       samples prepared; it provides reliable sample manipulation given
       the electric and magnetic nature of the technology; and it offers
       complete walk-away automation, bringing the push-button experience
       of a sequencer to sample prep.  I'm proud to bring a solution to
       the market that is accessible for all labs, especially labs with
       lower budgets (which are the majority). Now small core labs can
       provide low-cost, competitive solutions relative to commercial
       service providers, and larger labs can scale up their processes to
       make new sequencing technologies available to their customers.
       Individual labs at universities can now bring sequencers in-house
       for cost-effective, efficient, and reliable sequencing. So many
       applications, with huge potential impact for consumers!  Fewer than
       5M humans have so far been exposed directly to sequencing
       technologies, yet sequencing technologies and life sciences tool
       development is what propels the modern world of biology. The only
       other field that has experienced advancements faster than
       sequencing technologies over the past two decades is AI, if that
       gives a basis of comparison for how big this is.  This level of
       sample prep automation is new to genomics, new to the world! I'm
       excited to hear your comments, questions, thoughts, ideas - please
       share your insights and experiences to help us realize the full
       potential of this technology and make a tangible impact on science
       and society. And, go!
        
       Author : perceptron
       Score  : 34 points
       Date   : 2024-04-18 12:40 UTC (10 hours ago)
        
       | DHaldane wrote:
       | Fascinating technology - if I interpret it correctly it looks
       | like you're replacing lots of manual pipetting with a surface
       | that can scooch little drops around using electrostatics. And
       | then do a bunch of stuff you can't do with a pipette like
       | controlling temperature, mixing.
       | 
       | Have you found an increase in throughput from the device vs a
       | human with a traditional wet lab? Or is more about saving bio-
       | chemists some serious back pain?
       | 
       | Are there new experiments we can do now?
        
         | perceptron wrote:
         | Your assessment is more or less spot on. We are replacing many
         | pipetting steps with electric and magnetic manipulation of
         | samples on a surface.
         | 
         | Traditionally these operations when done manually (or even on
         | other automation) are done inside tubes. When these operations
         | are carried out inside tubes you have many limitations: you end
         | up using a lot of tips, when pipetting manually some workflows
         | require special techniques to pipette handle the samples. These
         | operations are also extremely painful when do them over and
         | over again -- very tedious and very easy to make a mistake.
         | 
         | Yes we have seen increase in throughputs relative to human.
         | Most humans (often) process samples in batches of 8 / 12
         | samples. To give you a sense of the length of the workflow in a
         | lab it can range from two hours to two days. The Callisto
         | system can process anywhere from 1 - 24 samples for many
         | workflows and is software controlled. It not only eliminates
         | the manual steps: it provides at least 3X the throughput with
         | 15 mins setup time, provides reproducible results and improves
         | quality.
        
       | waiquoo wrote:
       | How does your technology compare to Nuclera's chip based
       | system?https://www.nuclera.com/technology/
        
       | Vt71fcAqt7 wrote:
       | So this would be a step before feeding the outputs to something
       | like one of illumina's machines?
        
         | perceptron wrote:
         | Hello! Yes this it the step that comes before Illumina machines
         | as well as every other sequencer on the market. Samples coming
         | out of Callisto can also feed into other sequencers including
         | PacBio, Oxford Nanopore, Element, Ultima and other sequencer on
         | the market.
        
       | _ihaque wrote:
       | Hi Udayan - nice to see another shot at electrowetting
       | microfluidics in this space.
       | 
       | 1. How does your technology or product offering distinguish
       | itself from prior attempts like NeoPrep (nee Advanced Liquid
       | Logic) from Illumina or Voltrax from ONT?
       | 
       | 2. How "hackable" is the offering for power users to implement
       | custom protocols on the instrument and consumables?
        
         | perceptron wrote:
         | Great questions actually. To your second question, the current
         | offering of the system is not hackable -- both instruments and
         | consumables.
        
         | perceptron wrote:
         | In response to your first question, there are notable
         | differences between the NeoPrep and Callisto, and between
         | Voltrax and Callisto.
         | 
         | NeoPrep / Voltrax vs Callisto:
         | 
         | - NeoPrep and Voltrax primarily use electrowetting to
         | manipulate samples and droplets. In contrast, Volta Labs'
         | Callisto uses electrowetting where appropriate and employs
         | other traditional and non-traditional technologies for
         | different droplet manipulation operations. For instance (in the
         | linked video), we demonstrate the use of a standard pipettor
         | for transferring liquids from tubes on the electrowetting
         | surface in our video.
         | 
         | - While NeoPrep and Voltrax have limitations in certain
         | workflow capabilities compared to Callisto, they also surpass
         | Callisto in other aspects. For example, they have lower
         | throughput and lack batch level flexibility. Unlike the Volta
         | Callisto system, these two systems cannot process raw samples
         | such as blood, saliva, or cells. However, the Volta Callisto
         | system can extract DNA/RNA from raw biological samples,
         | including blood and saliva. On the contrary both the Voltrax
         | and NeoPrep systems can perform onboard/on-chip PCR and measure
         | DNA quantities using optical sensors, capabilities that the
         | Volta Callisto system currently lacks.
         | 
         | - The NeoPrep system used a PCB cartridge which had significant
         | robustness issues, and the entire PCB was disposable.
         | Similarly, the Voltrax system's LCD display is disposable after
         | each run. On the other hand, the Callisto system uses a simple
         | plastic component as the disposable.
         | 
         | - User interaction with NeoPrep and Voltrax can be quite messy,
         | requiring users to fill oil through channels and dispense
         | reagents/samples through small holes. The Callisto system,
         | however, accepts standard tubes as inputs and outputs,
         | eliminating the need for users to learn new techniques for
         | loading/unloading samples into the system.
        
       | handbasket_ride wrote:
       | The Volta Labs employee reviews on GlassDoor paint a picture of a
       | high functioning team feeling crippled by absent or dysfunctional
       | management. There are some high ratings but to my eye they look
       | like they were probably written by management.
       | 
       | Are you confident you can launch and support a complex innovative
       | product successfully with an apparently disgruntled and depressed
       | technical team?
        
         | qkucy wrote:
         | I'm honestly surprised their Glassdoor rating is as high as it
         | currently is- perhaps review-washing? A year back when I
         | interviewed for a position there, the rating was much lower, in
         | the 2-3 range.
        
           | circumlocution_ wrote:
           | They have a 2.6 if all 15 current reviews are included. I
           | believe you're right about review-washing; negative reviews I
           | saw a year ago appear to have been removed.
        
         | ub-volta-toss wrote:
         | Employee reviews are a very underrated way to judge a company.
         | Especially one that offers breakthrough tech
        
       | ub-volta-toss wrote:
       | that vimeo is just a guy talking? lets see some science!
       | 
       | i think nato built something like this at uBiome, but it never
       | saw use. another yc that scrubbed the glass-door reviews
        
         | ub-volta-toss wrote:
         | Further reflection- this video is a little sketchy. it has
         | subtle flaws that look like red flags
         | 
         | - Nobody who works in a lab would call screw cap tubes 'these
         | little tubes'
         | 
         | - Shows no action from machine
         | 
         | - How is machine supposed to open 'these little tubes'? It
         | can't unscrew them.
         | 
         | - If the operator starts the machine with open screw-cap tubes
         | (usually full of expensive things) how would the operator (or
         | robot) close the tube for the rest of the run? Leaving it open
         | is bad, seems like opening the machine should be bad...
         | 
         | I think if this company actually had a working machine, they'd
         | show it working
         | 
         | edit: glassdoor reviews are insaaaane. if people are willing to
         | leave reviews like that at a company this small, its gotta be
         | worse than they're even describing.
         | 
         | so much promise in the bio space absorbing tech, so much peril
         | when tech tries to bio
        
           | perceptron wrote:
           | Thank you for the valuable criticism.
           | 
           | - We created this video specifically for the HackerNews
           | community, opting for simple language to cater to a broad
           | audience. - We are open to filming again to showcase more of
           | the technology. - The Callisto system doesn't unscrew the
           | caps; users do that before using it. - Neither the robot nor
           | the operator close the tubes for the remainder of the run.
           | They're left open for the pipettor. The reagents and samples
           | in the tubes are consumed throughout the process.
        
       | startingQB wrote:
       | This is fascinating!
       | 
       | 1. How do you ensure the reliability of the Callisto system, and
       | what evidence can you provide that demonstrates its performance
       | and consistency in different laboratory settings?
       | 
       | 2. What are the technical limitations of the current version of
       | your system, and how do you plan to address these in future
       | iterations?
       | 
       | 3. What are the long-term goals for Volta Labs, and how do you
       | plan to evolve your technology to meet future market needs?
       | 
       | 4. Could you provide details on the initial and operating costs
       | of the Callisto Sample Prep System? Considering you mention
       | lowering the cost for small labs, how does the investment compare
       | in terms of ROI and scalability? How does it compare for
       | university labs traditionally use student volunteers for manual
       | tasks?
       | 
       | 5. What is the significance of the name 'Callisto' for your
       | sample prep system? Is there a connection to its namesake, either
       | the nymph or the moon of Jupiter, that reflects the system's
       | qualities or capabilities?
        
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       (page generated 2024-04-18 23:00 UTC)