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!
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?
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.
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 (née 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?
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.
Great questions actually. To your second question, the current offering of the system is not hackable -- both instruments and consumables.
This is awesome. I am highly interested in the BioTech space and happened to work with electro-wetting for zero gravity space applications almost 10 years ago!
This is such a cool application of the tech. Everything is accelerating in biotech.
We were using electro-wetting as a low power heat pipe on the Space Station, since heat doesn’t dissipate the same way there as it does on Earth. The tech I built with some engineers used these tiny DC to DC high voltage transformers that would step up the voltage from the 18V power supply to something like 450V on the circuit board to enable the electro-wetting heat pipes to move water droplets.
Would love to chat sometime if you are ever interested.
For reference, our very scrappy POC for the space station: https://ntrs.nasa.gov/api/citations/20190006008/downloads/20...
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? What is the value proposition for university labs that 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?
1. We have a rigorous validation plan for ensuring that the applications on the platform perform robustly. We also operate in an industry where the standards are very high and samples being processed are previous and there are no excuses for failures. Moreover we have deployed with several customers in 2023, results of which have been showcased at premier genomics conference like AGBT. They are all published on our website here: https://www.voltalabs.com/resources
2. Some technical limitations of the platform include its inability to do PCR or onboard implication, there are also limitations on range of volumes we can work with. We plan to address these in the future.
3. Our system actually leverages an advanced form of electrowetting, magnetic manipulation of samples and thermal control in combination with liquid transfer technologies like pipettors. Our roadmap includes advancing all of these underlying technologies: for example being able to go to higher or lower temperatures. If you also think about the declining cost of sequencing, the cost of sample prep needs to go down relative to the cost of sequencing: we are going to advance the technology to drive the cost curve down. We might potentially expand into other applications beyond sequencing: those include synthetic biology, proteomics to name a couple.
The name 'Callisto' refers to one of Jupiter's moons. It indeed mirrors the system's qualities and capabilities. Specifically, the name signifies the grandeur of this planet and its moons.
So this would be a step before feeding the outputs to something like one of illumina's machines?
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.
Congrats Udayan on the launch!
It’s really neat to see the open-face nature of this product as compared to others doing EWOD with a second immiscible phase / a glass top plate that the droplet is squished under — makes it much easier to do IO to the chip.
Are the chips disposable, to accomodate contamination constraints, or is there some on-site surface reconditioning that we can do to refurb the chips?
Interesting to note that this is down-scaled from some of your older prototypes. What design tradeoffs made you go fron large open faced arrays to a set of smaller arrays?
Hi Dash!
The system uses a disposable plastic consumable that gets replaced after each run.
In terms of design trade offs, its not just a electrowetting system. It employs complex magnetic manipulation, thermal controls and other forms of sample manipulation. We had to work under these constraints.
How does your technology compare to Nuclera's chip based system?https://www.nuclera.com/technology/
We do not have firsthand experience with the Nuclera's chip based system. But there are some key differences based on what we can find online:
- their system uses display technology based backpanel from Eink to activate the electrodes. The display itself could be the consumable that is disposed after each run (we are not sure from their website). The technology is suited for manipulating very small volumes. Looks like they have picked applications that span enzymatic DNA synthesis and protein eexpression
- the Callisto system uses standard PCBs and plastic surface that interfaces with the droplets. The PCBs are not disposed after each run, while the plastic surface is. We can also handle a large dynamic range of volumes in liquids making it suitable for more standard molecular biology workflows.
we already have hackable, $26k solutions for single cell library prep: https://labautomation.io/t/10x-scrna-seq-library-prep-26k/30
what i am curious about is techniques to scale biological data generation & scientific progress via large-scale single-cell biological profiling
Awesome to see this!!!
I am curious about the solution you have on there:
- Is this built on Opentrons or something similar?
- Was this an off the shelf solution or something you built?
- I would also be curious about the sample batch size
Note that the Volta solution does not require app development or method development. Many off the shelf sample prep workflows are readily available on the Callisto system.
This seems interesting for my work. Can it run DNA extractions on environmental samples? Have you benchmarked against any synthetic communities?
We have not processes any environmental samples yet. Previously we have looked at Zymo microbial community, that as far as it goes with synthetic communities. But with some fluidics focussed work, I dont see it would not be possible to extract DNA from environmental samples.
What specific samples did you have in mind?
I have high biomass samples from soda lakes (high salinity and alkalinity). Other people in my lab work with soil samples, samples from methane seeps, and low biomass samples from rocks. It could also be useful for wastewater samples.
What’s the general pricing structure? It sounds like you can do 24 samples at once? Approx how much does each sample end up costing (for dna extraction and library prep?).
Those sample might be hard to process on the current form of Callisto. The instrument is priced at $125k. Your per sample cost comes down to $20 - $100 depending on the workflow.
For several workflows Volta provides reagents as well. So that will be your all in cost essentially.
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
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
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.
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?
Yes - I'm confident in our ability to build and support our product for several reasons. We've recruited exceptional talents who believe in Volta's mission, and we are making deliberate adjustments to better listen, learn, and support them. I agree that the Glassdoor reviews are challenging. However, these reviews, along with employee feedback, hiring, and exit insights, are instrumental in actively positioning the right people and systems to improve the overall employee experience. For instance, we've been hiring experienced leaders to better mentor our team.
Moreover, we've undergone several transformations as a business rapidly over the past year. We transitioned from an R&D focus to a commercial focus, almost doubled our team size (and continue to grow), and now, with our commercial launch, we're evolving again. There have been some tough growing pains, and change isn't always easy. But we're committed to building a sustainable business, and the way to achieve this is by fostering an environment that encourages openness, collaboration, and innovation.
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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.
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.
Employee reviews are a very underrated way to judge a company. Especially one that offers breakthrough tech