Archive for July 2018

Armonica Technologies LLC (now Inc)

In my last post I put together a list of 41 companies which either have a DNA sequencing platform on the market, or in development. There is really only one company that dominates this market (Illumina) so most of the players are either niche plays or startups. Armonica is one such early stage startup.

Business

They appear to have raised 1.5MUSD [1]. Before looking into the technology, there are a number of things that stand out about Armonica. Firstly it’s an LLC, typically the received wisdom for creating a venture funded tech startup is to create a Delaware C-Corp. From what I can tell, creating an LLC could be problematic for traditional investors (who might want preferred shares for example) [2] (appears to now be listed as Armonica Technologies Inc. [13]).

The next thing that stands out is the list of “Board Of Directors/Executive Leadership”.

There are 5 people on this list [3], but of them only Steven Brueck (CSO) and Scott Goldman (CEO) appear to be part of the company (the rest are investors). Sally Corning is listed as co-founder, and a partner at a fund, which seemed odd to me.

A LinkedIn search shows Scott and one other senior consultant. The CSO is a university professor so most likely doesn’t do much at the company day-to-day. An SBIR entry suggests they have 23 employees which seems surprisingly high [12].

Overall, it seems to be seed stage, the company was founded in 2015 [4].

Technology

Armonica is an optical nanopore DNA sequencing company. Optical nanopore approaches use a nanopore to control the motion of a strand of DNA but an optical readout (as opposed to direct electrical detection [5]). Armonica are not the only company to propose the use of an optical nanopore, Quantapore have presented a protein nanopore, FRET based concept too. But the method suggested in Dr Brueck’s patents [6] and paper [7] differs significantly. Firstly, the fabrication methodology they’re suggesting is quite novel, and secondly the optical readout is label-free (using surface plasmonic resonance).

First up, fabrication. There are a number of novel features here firstly they’re using interference lithography to define their features. Interference lithography is one technique that lets you beat the diffraction limit and create features smaller than the wavelength of light. It does this by using the interference between two coherent light sources to define the pattern. Pretty neat! The downside is of course that you are limited to periodic structures, but that seems fine for nanochannels and they present SEM images with channels as small as 100nm.

After using interference lithography to lay down photoresist they then lay down Silica nanobeads, after which they heat the whole thing, baking out the photoresist and sintering the silica to create the final structure. Neat! The exact advantage of using nanobeads over other deposition methods is less clear to me (I’m no expert) and some quick googling brings up some alternative methods for creating enclosed nanochannels [8]. It would be interesting to dig further into this aspect of the technology, and contrast the various approaches here.

With nanochannels in place, they can DNA through them (see below) . This is where their paper finishes up. The Silica is transparent, so they can image YOYO stained double stranded DNA right through it. They note that in the small (100nm) channels, it’s harder to get the DNA moving through, and that it moves more slowly (driven only by capillary action here).

DNA imaged in nanochannels from [7].

The above is based on published work out of Brueck’s lab. The patents (and brief description on the website) mix things up a bit, and describe a tortuous nanopore. In the patent tortuous nanopores are rather aptly described as “complex, 3D paths, similar to the spacings and open paths created when oranges are piled up in the local supermarket”. So, the idea is rather than precisely defining a nanopore, you can stochastically define them with these piles of silica nanobeads. You can also use a more traditional deposition method to (somewhat selectively) close apertures in this “tortuous nanopore”. This also seems like a rather neat idea. The tortuous nanopore concept potentially provides a method for slowing translocation (generally an issue with solid state nanopore systems) and for generating small apertures than available with traditional fabrication processes. It makes me wonder if the system couldn’t be used for ionic current detection (or perhaps there is too much stray ionic current, or other issues).  From what I can tell the system uses a bias voltage to drive the strand through the pore.

The base detection process is probably the least detailed part of the patent. My understanding is it essentially states that they’ll use surface plasmon resonance, and that there are a bunch of ways of doing that. Using SPR for DNA sequencing isn’t a new idea, and a quick google brings up grants for as early as 1999 [9]. But I would have to do more reading to know how practical it is here. Interestingly another company (Redondo Optics [10]) has an SBIR grant [11] for using SECAR SPR for DNA sequencing. The CEO of Redondo optics is also on the Armonica SAB. With more time this would be an interesting avenue to follow up.

For the moment however, I leave this brief review here. Overall the Armonica technology seems to have a number of interesting novel aspects. If you have any further insights into the technology, or would help to chat about DNA sequencing drop me a line (new at sgenomics dot org), or leave a comment!

 

[1] https://www.abqjournal.com/1050880/unm-technology-accelerates-genomic-sequencing.html

[2] https://mashable.com/2016/01/27/startup-business-structure/#eSxUGPb_qGqX

[3] Currently listed on the website are:

David Blivin, MBA Managing Partner, Cottonwood Technology Funds

Steven R. J. Brueck, Ph.D. Chief Scientific Officer, Armonica Technologies

Sally Corning, MBA Co-Founder & Partner, Sun Mountain Capital

Scott Goldman, MBA President & Chief Executive Officer, Armonica Technologies

Waneta Tuttle, MBA, Ph.D. Fund Manager, Tramway Venture Partners

[4] SEC Filing https://www.sec.gov/Archives/edgar/data/1714729/000171472917000001/xslFormDX01/primary_doc.xml

[5] Most other nanopore companies propose detection through the blockage of ionic currents, or tunneling currents.

[6] US9927397: https://patentimages.storage.googleapis.com/56/92/ad/2b5ef43d1f4c47/US9927397.pdf

US20160377590A1: https://patentimages.storage.googleapis.com/d1/8a/16/0bc8e6aafcf270/US20160377590A1.pdf

[7] http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.172.7987&rep=rep1&type=pdf http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.172.7974&rep=rep1&type=pdf

[8] https://www.princeton.edu/~chouweb/publications/148%20Austin_Scanning%20the%20Controls_IEEE%20Nanotech_2002.pdf

[9] http://grantome.com/grant/NIH/R21-HG002102-01

[10] http://www.redondooptics.com/

[11] https://www.sbir.gov/sbirsearch/detail/1031029

[12] https://www.sbir.gov/sbirsearch/detail/1490917

[13] https://www.sec.gov/Archives/edgar/data/1714729/000171472917000001/xslFormDX01/primary_doc.xml

DNA Sequencing Companies (Updated May 2020)

Below is a list of 40+ companies who either have a DNA sequencing platform on the market, or where there’s public information that they are developing a DNA sequencing/mapping platform. Below the main table is a list is mapping companies, many of which have sequencing related IP/approaches. There are a few cases where it’s not clear if the company is still active, I’ve tried to note this. If have any information on these companies, know of any others, or would just like to chat about sequencing companies/the sequencing market in general, feel free to email me (new at sgenomics dot org).

Disclosure: I’ve worked at a few of these companies, all the information presented here is based on public information.

Due to the width of the table, it’s best viewed on desktop.

Name Further Info Blog post Status Detection method Single mol? Chemistry Location
Apton Biosystems Company Website 1 2 Series A/B Optical Yes ? Pleasanton, CA
Armonica Technologies LLC Company Website Blog Seed? Optical-nanopore Yes Direct (label free) New Mexico – USA
Base4 Company Website Blog Series A+? Microdroplet/optical (+nanopore) No Pyrophosphorolysis Cambridge – UK
BGI (inc. Complete Genomics) Company website Blog IPO Optical No SBL/SBH Mountain View – USA
Caerus Molecular Diagnostics Company Website Blog Seed – 2014 Optical Yes SBS Mountain View – USA
Centrillion Company Website Blog Series B Optical No SBS on Array Palo Alto – USA
Cygnus Biosciences News Article Blog Series B Optical No SBS Beijing – China
Depixus (was Picoseq) Company Website Blog Series A Unzipping force Yes SBL/SBH/Interference Paris
Direct Genomics Company Website Blog Unknown Optical Yes SBS Shenzhen – China
DNAe (DNA Electronics) Company Website   Series A + X? ISFET No SBS (unlabelled) London – UK
Electronic Biosciences Company Website   Seed+? Protein-nanopore Yes Direct (label free)? San Diego – USA
ElectroSeq Genomeweb Article   Pre-seed? ISFET No SBS? New Mexico – USA
Element Biosciences Blog Blog Series A Optical? No SBS? San Diego – USA
Esper Biosciences SBIR Note   Seed? Nanopore Yes ? Ithaca, NY
Genapsys Company Website Blog Series C Debye layer? No SBS Redwood City – USA
Genedra Biotech Ltd Company Website (dead)   Dead? Optical Unknown SBS Beijing – China
Geneseque Company Website   Pre-seed? Optical Yes SBH? Norway
Illumina Company Website   IPO Optical No SBS San Diego – USA
iNanoBio Company Website Blog Seed Nanopore – FET Yes Direct Arizona – USA
inSilixa Company Website Blog Series A Optical+Other No SBS/Hybridisation Sunnyvale, CA – USA
Intelligent biosystems (Qiagen) Company Website   Acquired Optical No SBS? Netherlands
Ion Torrent (ThermoFisher) Company Website   Acquired ISFET No SBS (unlabelled) Massachusetts – USA?
Lasergen (Agilent) Company Website   Acquired Optical No SBS Texas – USA
Lightspeed Genomics Company Website   Acquired? Optical Unknown Unknown Santa Clara – USA
Molecular Research Limited (Mobious) Company Website   Seed? Alive? Molecular Resonance Sequencing Unknown Unknown Exeter – UK
Northshore Bio Company Website Blog Series A Solid-state nanopore Yes Direct (label free) Camas, WA
Omniome Company Website   Series A+ Undisclosed Undisclosed SBB San Diego – USA
Oxford Nanopore Technologies Company Website   Series I+ Protein-nanopore Yes Direct (label free) Oxford – UK
PacBio Company Website   IPO Optical – ZMW Yes SBS Menlo Park – USA
Personal Genomics/CrackerBio Video Blog Series B Optical Semiconductor Yes SBS Taiwan
Qiagen Company Website     Optical No SBS Germany
Quantapore Company Website   Series C Optical-Nanopore Yes All bases labelled Menlo Park – USA
Quantum Biosystems Company Website   Series B Nanopore/gap Yes Direct (label free) Osaka – Japan
QuantumDX Company Website Blog Series C+ Nanowire Yes/No Tags or SBS Newcastle – UK
QuantumSi Company Website Blog ? Optical – ZMW Yes SBS Guilford, CT
ReadCoor Company Website   Series A Optical No? SBS? Cambridge, MA – USA
Roche (Genia Technologies) Company Website Blog Acquired Protein-nanopore Yes SBS Santa Clara – USA
Roswell Biotechnologies Company Website Blog Series A Nanogap Yes SBS-like San Diego – USA
SeqLL Company Website   Series A Optical Yes SBS Massachusetts – USA
Single Technologies Company Website Blog Seed+ Optical Yes SBS? Stockholm – Sweden
SingularBIO Company Website (dead) Acquisition Acquired Unknown Unknown Unknown San Francisco – USA
Singular Genomics Note Blog Series B Optical? Various Various San Diego – USA
Stratos Genomics (Roche) Company Website Blog Acquired Nanopore (protein?) Yes Seq-by-Expansion Seattle – USA
Ultima Genomics   Blog Seed Optical No SBS Newark, CA – USA
Universal Sequencing Technology Corporation Company Website Blog Seed? Nanopore Yes Various Stoughton, MA – USA
XGenomes Company Website   Seed? Optical Unknown Unknown Boston – USA

Mapping

Name Further Info Blog post Status Detection method Single mol? Chemistry Location
Genome Surveillance, Inc. Online note   Pre-seed Unknown Yes? Restriction map? Wisconsin – USA
BioNano Genomics Company Website Blog Series D Optical Yes Nicking/fluorescent tags San Diego – USA
OpGen Company Website   IPO Optical Yes Restriction mapping Maryland – USA
Nabsys 2.0 Company Website   Series E+ Solid-state nanopore Yes hybridized tags Rhode Island – USA
NanoString Technologies Bio IT World Article   Series E+ Optical No hybridized tags Seattle – USA
Ontera Company Website   Series C? Solid-state nanopore Yes Ionic? Santa Cruz – USA

SBS: Sequencing-by-Synthesis

SBH: Sequencing-by-Hybridization

SBB: Sequencing-by-Binding

Warning
Warning
Warning
Warning

Warning. Please fill out the form correctly.