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Ask HN: What interesting problems are you working on?

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Re: Ask HN: What interesting problems are you working on?

#441

Post by quickthrower2 »

philip1209 wrote: post #168

I'm working to reinvent personal websites. My goal is to replace social media with personal sites + newsletters, which are more distributed, privacy-friendly, and calm. https://postcard.page The product seems simple, but there are so many opportunities for optimization. There's caching, CDNs, custom domain support, dynamically-generated open graph images, image optimizations, email sending, email reputations, analyti…

Nice. Feels like you are a “Ghost” or “Bearblog” kind of offering. Always good to have more choice here.

Re: Ask HN: What interesting problems are you working on?

#442

Post by koeng »

iron2disulfide wrote: post #85
koeng wrote: post #6

A little while ago, a patent for high throughput DNA synthesis using silicon chips went off-patent, so I have been learning analog IC chip design to build an open source high-throughput DNA synthesis chip. If it works, and I sold them at cost, it would reduce the cost of oligo pool synthesis by ~100x and possibly gene synthesis by 10x. For about 8-9 years now my goal has been to build a cell from scratch for less tha…

(Digital) chip designer here: this is super cool. What tech node are you targeting? Have you checked out any of the free open-source tools and PDK from Skywater, Google, eFabless and co?

I'm planning on using the chip ignite program! They can build the chip I need - the harder bit is figuring out the coatings needed (sputter coating post-processing is needed to be compatible with the chemistry).

I am pretty new to chip design but know the DNA space quite well - I would love to do a call, if possible, because I have lots of noob questions about chip design and chip design tools. Happy to share anything about the biological side in exchange!

Re: Ask HN: What interesting problems are you working on?

#444

Post by koeng »

LunarCamper wrote: post #30
koeng wrote: post #6

A little while ago, a patent for high throughput DNA synthesis using silicon chips went off-patent, so I have been learning analog IC chip design to build an open source high-throughput DNA synthesis chip. If it works, and I sold them at cost, it would reduce the cost of oligo pool synthesis by ~100x and possibly gene synthesis by 10x. For about 8-9 years now my goal has been to build a cell from scratch for less tha…

Is there a page, blog, twitter account, newsletter, Github repo or anything to follow this? I have no knowledge in this space so I'm of no help, but I'm very interested in the prospect of this stuff becoming more accessible!

Github here - https://github.com/koeng101/dnachips

It is a bit dead when it comes to a git, since I am trying to get the first machine needed, which is a DNA synthesizer (asked about that here https://groups.google.com/g/diybio/c/V3OYVBxaH04 for example).

The idea is that with a traditional DNA synthesizer I can have positive controls of the chemistry, and develop a chip that can fit inside the flow cell of the existing synthesizer. In biotech, everything goes wrong a bit more often than in computer science, so the focus lately has been getting my hands on a working synthesizer. This is a tried and true method of getting chip synthesis working.

If that works, I'd like to provide the chip at cost for integrators, as well as develop a functioning full product for integration with some bots I'm building for my official work.

Personal website is here - http://keonigandall.com

Re: Ask HN: What interesting problems are you working on?

#445

Post by samhuk »

Javascript and ORMs have a (fairly well-known) interesting set of problems:

* There aren't many

* Those that you can find, don't support Typescript, so it's all guesswork.

* Don't have much (if any) support for related data queries

So I've been working on a ORM for PostgreSQL and Typescript for a few months now in my spare time [0]. It's been probably one of the biggest, challenging, and interesting problems I have embarked on solving.

Some things i've observed along the road:

* Typescript is weird and wonderful when you push it to it's limits, particularly around recursive structures. Strange workarounds exist, nicely provded by all of the two Stack Overflow Typescript gurus that exist.

* PostgreSQL doesn't have some of the features that you would expect from other DB technologies (i.e. certain table alterations, limit on update and delete, etc.). Weird and wonderful workarounds exist, but it always leaves you thinking _why aren't those workarounds just the de facto way for doing those things?_.

[0] https://github.com/samhuk/ts-pg-orm

Re: Ask HN: What interesting problems are you working on?

#446

Post by koeng »

Dracophoenix wrote: post #109
koeng wrote: post #6

A little while ago, a patent for high throughput DNA synthesis using silicon chips went off-patent, so I have been learning analog IC chip design to build an open source high-throughput DNA synthesis chip. If it works, and I sold them at cost, it would reduce the cost of oligo pool synthesis by ~100x and possibly gene synthesis by 10x. For about 8-9 years now my goal has been to build a cell from scratch for less tha…

> so I have been learning analog IC chip design to build an open source high-throughput DNA synthesis chip. Any resources and books you'd recommend?

As a software engineer, verily and the like just didn't make as much sense to me as chisel. Got this book and have been very slowly working through it - https://www.amazon.com/Digital-Design-Chisel-Martin-Schoeber...

Efabless's chip ignite program is also great - check it out! https://efabless.com

Re: Ask HN: What interesting problems are you working on?

#447

Post by koeng »

hcks wrote: post #250
koeng wrote: post #6

A little while ago, a patent for high throughput DNA synthesis using silicon chips went off-patent, so I have been learning analog IC chip design to build an open source high-throughput DNA synthesis chip. If it works, and I sold them at cost, it would reduce the cost of oligo pool synthesis by ~100x and possibly gene synthesis by 10x. For about 8-9 years now my goal has been to build a cell from scratch for less tha…

I don't understand why, if it really worked, the org holding the patent didn't do anything of it.

They did. This runs genscript's high throughput DNA synthesis platform. They actively sell the result as their oligo pool product.

Re: Ask HN: What interesting problems are you working on?

#448

Post by koeng »

jfim wrote: post #97
koeng wrote: post #6

A little while ago, a patent for high throughput DNA synthesis using silicon chips went off-patent, so I have been learning analog IC chip design to build an open source high-throughput DNA synthesis chip. If it works, and I sold them at cost, it would reduce the cost of oligo pool synthesis by ~100x and possibly gene synthesis by 10x. For about 8-9 years now my goal has been to build a cell from scratch for less tha…

Not knowing anything about this field, what could someone do with such a chip? Is it something like a 3D printer where you can get a rough but usable finished product, or is it more like a "if you want to make bacterium X produce Y product, you need to do X, Y, Z, W, etc." and the chip is used to do one of the steps.

It is more like the X Y Z W. However, the X Y Z W bits I am working on as well (https://github.com/TimothyStiles/poly , https://github.com/TimothyStiles/allbase , trilo.bio, freegenes.org). Going for fully automated "make bacterium X produce molecule Y", but still a while away (but surprisingly not THAT far off)

Re: Ask HN: What interesting problems are you working on?

#449

Post by koeng »

imnotreallynew wrote: post #242
koeng wrote: post #6

A little while ago, a patent for high throughput DNA synthesis using silicon chips went off-patent, so I have been learning analog IC chip design to build an open source high-throughput DNA synthesis chip. If it works, and I sold them at cost, it would reduce the cost of oligo pool synthesis by ~100x and possibly gene synthesis by 10x. For about 8-9 years now my goal has been to build a cell from scratch for less tha…

Do you mean completely from scratch? If so, why would one want to do that versus taking an existing cell and injecting custom DNA?

You can't jump over fitness troughs. For example, full tRNA recoding. Plus, it is neat to make life from chemicals.

Re: Ask HN: What interesting problems are you working on?

#450

Post by koeng »

neodypsis wrote: post #44
koeng wrote: post #6

A little while ago, a patent for high throughput DNA synthesis using silicon chips went off-patent, so I have been learning analog IC chip design to build an open source high-throughput DNA synthesis chip. If it works, and I sold them at cost, it would reduce the cost of oligo pool synthesis by ~100x and possibly gene synthesis by 10x. For about 8-9 years now my goal has been to build a cell from scratch for less tha…

Pretty cool. May I ask, what is your background? And, what resources are you using to learn about analog IC chip design?

~10yr of synthetic bio, did 4yr of mitochondrial engineering + directed evolution at UCI, then ran the FreeGenes Project for 3yr at Stanford.

Chisel for programming it (great little lang/project) https://www.amazon.com/Digital-Design-Chisel-Martin-Schoeber...

Efabless PDKs - https://efabless.com/

Other than that, lots of trial and error. Hardware people are brutal with their acronyms, so it really comes down to a lot of stumbling around and reading whatever I can.

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