perceptron's comments

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.

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.

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.

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 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?

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.

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.

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.

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.

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.

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.

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.

Interesting thought. The plastic tape is just a representative raw material. The plastic tape can totally be replaced with biodegradable material.

The key idea is to start with something with no structural integrity, the tape as a sheet and give it a good strength to weight ratio by folding it into tube.

ProtoPiper is an attempt to bring the human back to material interaction, like in traditional craft practices. It is more than just a prototyping device. It helps you think about materials, gravity and structures.