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COMMENT PAGE FOR:
DIR Launch HN: Volta Labs (YC W19) â Easier sample prep for genomics
dhash wrote 1 day ago:
Congrats Udayan on the launch!
Itâs 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 â 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?
perceptron wrote 1 day ago:
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.
ben-ray wrote 1 day ago:
we already have hackable, $26k solutions for single cell library prep:
[1] what i am curious about is techniques to scale biological data
generation & scientific progress via large-scale single-cell biological
profiling
URI [1]: https://labautomation.io/t/10x-scrna-seq-library-prep-26k/30
perceptron wrote 1 day ago:
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.
human_person wrote 1 day ago:
This seems interesting for my work. Can it run DNA extractions on
environmental samples? Have you benchmarked against any synthetic
communities?
perceptron wrote 1 day ago:
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?
human_person wrote 1 day ago:
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.
Whatâs 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?).
perceptron wrote 1 day ago:
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.
startingQB wrote 2 days ago:
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 systemâs qualities or
capabilities?
perceptron wrote 1 day ago:
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.
perceptron wrote 2 days ago:
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: [1] 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.
URI [1]: https://www.voltalabs.com/resources
ub-volta-toss wrote 2 days ago:
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 2 days ago:
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 2 days ago:
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.
handbasket_ride wrote 2 days ago:
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?
perceptron wrote 2 days ago:
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.
ub-volta-toss wrote 2 days ago:
Employee reviews are a very underrated way to judge a company.
Especially one that offers breakthrough tech
qkucy wrote 2 days ago:
Iâm 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 2 days ago:
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.
_ihaque wrote 2 days ago:
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?
perceptron wrote 2 days ago:
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.
perceptron wrote 2 days ago:
Great questions actually. To your second question, the current
offering of the system is not hackable -- both instruments and
consumables.
Vt71fcAqt7 wrote 2 days ago:
So this would be a step before feeding the outputs to something like
one of illumina's machines?
perceptron wrote 2 days ago:
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.
waiquoo wrote 2 days ago:
How does your technology compare to Nuclera's chip based system?
URI [1]: https://www.nuclera.com/technology/
perceptron wrote 1 day ago:
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.
DHaldane wrote 2 days ago:
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 2 days ago:
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.
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