ASeq Newsletter

The ASeq Newsletter explores advancements and challenges within the sequencing technology landscape, focusing on industry dynamics, clinical applications, and market competition. It critically examines the role of major companies like Illumina, emerging technologies, and the impact of sequencing in diagnostics and oncology.

Sequencing Technology Genetics and Diagnostics Market Dynamics Clinical Applications Industry Analysis Technological Innovations Company Profiles

The hottest Substack posts of ASeq Newsletter

And their main takeaways

Some Thoughts On 10X Genomics

36 implied HN points • 18 Jan 24
🔬 Science Genomics Competitors Market Growth
  1. Spatial revenue for 10X Genomics is increasing, while single cell revenue growth is slowing down.
  2. There may not be much growth expected in single cell applications for 10X Genomics, but spatial sequencing shows potential for growth.
  3. 10X Genomics faces competition in the single cell market, but may retain a significant market share.

Protein Sequencing And Nanopore Current Ranges...

29 implied HN points • 02 Mar 24
🔬 Science Biology Chemistry Technology Research Innovation
  1. Protein sequencing using nanopores is a topic of interest, with a recent study highlighting a large state space of 10^25 and using an Oxford Nanopore's R9.4.1 pore with a range of ~10pA.
  2. Investigating patents can provide insights into the current range for DNA sequencing and can spark further contemplation about the future of protein sequencing using nanopores.
  3. The detailed post on protein sequencing and nanopore current ranges is available for paid subscribers, emphasizing the exclusivity of the content.

Some Notes On the MiSeq Flowcell

29 implied HN points • 27 Feb 24
🔬 Science Instruments Construction Materials Measurements Research
  1. The MiSeq flowcell consists of a plastic outer shell with a glass flowcell that clips open and closed.
  2. Measurements indicate a cover glass thickness of around 150um and a 100um channel height on a 1mm substrate.
  3. Unlike other flowcells, the MiSeq uses an all glass construction bonded with optical bonding material and borosilicate glass apertures.
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NextSeq 550 Imaging System and Fluidics Notes

36 implied HN points • 06 Jan 24
🕹 Technology Imaging System
  1. The NextSeq 550 Imaging System uses 6 identical imaging sub-modules.
  2. Each sub-module has its own camera, focusing electronics, and excitation sources.
  3. The post provides a summary of information based on one of these imaging modules and what's available in patents.

Illumina Reagent Volumes And Recipes

58 implied HN points • 27 Aug 23
🕹 Technology Research Sequencing Recipes
  1. Illumina does not provide public disclosure on reagent volumes, but you can measure them from kits.
  2. Recipe files for different Illumina sequencing platforms are available online to guide reagent amounts for the flowcell.
  3. A Google doc has extracted reagent steps for a deblock/incorporation cycle from various Illumina recipe files.

Compute In The HiSeq X

43 implied HN points • 15 Nov 23
🔬 Science Technology Hardware Storage
  1. HiSeq X uses an external compute server compared to MiSeq's internal computer setup.
  2. HiSeq X has larger storage volumes in various RAID configurations than MiSeq.
  3. HiSeq X offers about 4x the compute performance of MiSeq, while NovaSeq 6000 is 7 times faster than HiSeq X.

How Is A Flowcell Made? How Much Does It Cost?

36 implied HN points • 21 Dec 23
🔬 Science Technology Research Innovation
  1. The construction of a flowcell involves specific materials like Kapton KJ and Black Kapton.
  2. Some tests were done on the channel material, showing properties like self-extinguishing and tackiness at high temperatures.
  3. Channels are formed using a piece of cover glass and a section of the flowcell plastic material.

Everything Wrong With: "Illumina: The Measurement Monopoly" Part 1/8

43 implied HN points • 03 Nov 23
🕹 Technology Innovation Competition Industry Development Market
  1. Improvement in DNA sequencing has been slow compared to advancements in other industries like semiconductors
  2. Illumina's best selling sequencer is aging and there's a lack of significant competition in the market
  3. Technological advancements in sequencing are mainly incremental, with a focus on adding more cameras and making flow cells bigger

PacBio Acquires Apton!

58 implied HN points • 04 Aug 23
🕹 Technology Biotech Acquisition Sequencing Innovation Instrumentation
  1. PacBio is acquiring Apton BioSystems for approximately $110M to enhance their sequencing technology.
  2. The acquisition of Apton seems strategic for PacBio to develop a competitive high-throughput sequencing instrument.
  3. PacBio's new instrument lineup includes a range of sequencers from mid-range short reads to high-throughput long reads.

NextSeq 550 Imaging System

51 implied HN points • 11 Sep 23
🕹 Technology Imaging
  1. The post is about the NextSeq 550 Imaging System.
  2. The author discusses a HiSeq imaging module listing on eBay.
  3. The post is available only for paid subscribers.

Illumina Cluster Domination

29 implied HN points • 29 Jan 24
🔬 Science Genetics Sequencing DNA Research Technology
  1. Illumina sequencing uses clusters of DNA fragments, which can create issues if not all the fragments are the same.
  2. Unpatterned flowcells may have overlapping clusters leading to ambiguous results.
  3. Patterned flowcells use Exclusion Amplification to prevent cluster overlap and improve sequencing accuracy.

The Future of Sequencing

29 implied HN points • 04 Jan 24
🔬 Science Genomics Automation Diagnostics
  1. Sequencers should be as boring and simple as qPCR machines for easy use and accessibility.
  2. Automation in sequencing should focus on sample-to-answer approaches like the GeneXpert in diagnostics.
  3. Broader adoption of sequencing in clinical applications may require a cultural shift towards valuing diagnosis even without immediate treatment options.

10X Chromium Chip Patents

29 implied HN points • 02 Jan 24
🕹 Technology Patents
  1. The patents confirm findings from previous teardown and documentation processes.
  2. Negative pressure control is explained by the original location of output wells.
  3. Monitoring pressure carefully is crucial to avoid catastrophic blockages in the system.

10X Chromium Controller Component Cost Is Likely <$5000

29 implied HN points • 28 Dec 23
🔬 Science Research Technology Innovation Analysis Equipment
  1. The 10X Chromium Controller component cost is likely less than $5000, significantly lower than its original $35000 price tag.
  2. The key components like Thomas diaphragm pumps range from $200 to $400, making up a portion of the instrument's cost.
  3. Through further cost optimization, it's possible to produce a comparable instrument for much less than $5000.

Some Quick Thoughts On The ONT Accounts

21 implied HN points • 06 Mar 24
💰 Finance Analysis
  1. The ONT account numbers released today are not directly comparable to previous reports, especially for S1 (MinION) users who appear to have shifted to 'Indirect' sales.
  2. The number of S2 active customers has been revised up to 1210 from the previous estimate of 'around 1100', as stated at JPM.
  3. The count of S3 customers has been reduced to 84 from the previously mentioned '90 large high throughput' at JPM.

DNA Tubes - The HiSeq X Fluidic System

29 implied HN points • 13 Dec 23
🔬 Science Genomics
  1. The HiSeq X DNA sequencer contains about 100 meters of tubing inside for its fluidics system.
  2. The majority of the tubing in the HiSeq X appears to be around 1.5mm OD and 1mm ID, possibly made of PTFE.
  3. The fluidic path of the HiSeq X is structured similarly to the Solexa Genome Analyzer and uses components from the same vendors.

Comments On "An Illumina Sequencer in 2000"

21 implied HN points • 21 Feb 24
🕹 Technology Innovation Biotech Startups Sequencing Acquisition
  1. The acquisition of Solexa by Illumina involved strategic financial decisions and a combination of technology strengths to create a successful sequencing platform.
  2. There were missed opportunities and challenges due to financial constraints and differing viewpoints among key players in the sequencing technology industry.
  3. The early 2000s marked a period of significant innovation and the emergence of next-generation sequencing technologies, with various companies maneuvering to establish themselves in the market.

What The H*ll Is PPMSeq?

21 implied HN points • 17 Feb 24
🔬 Science Biotechnology Genomics Sequencing Bioinformatics
  1. PPMSeq is a duplex sequencing technique that ensures high accuracy reads by reading both forward and reverse strands of a double-stranded sequence.
  2. Ultima's PPMSeq works by amplifying both strands on the same bead and utilizing a tag to identify their presence, with errors causing radical dephasing which is taken care of by downstream software.
  3. Approaches to implementing PPMSeq on Ultima's platform involve reading both strands in both directions simultaneously or keeping the product on beads in the same orientation, each with its own challenges and considerations.

NanoString Is Dead

21 implied HN points • 05 Feb 24
💼 Business Technology Finance Patents
  1. NanoString faced financial troubles and declared bankruptcy.
  2. 10X Genomics won a lawsuit against NanoString, impacting their sales and potential for growth.
  3. NanoString's product nCounter platform had limitations and did not bring significant success, leading to their downfall.

Real-time Spatial Sequencing

21 implied HN points • 25 Jan 24
🔬 Science Biology Technology Research Innovation Genomics
  1. Real-time spatial sequencing involves obtaining a full time course of RNA as it's transcribed and cleared from cells.
  2. Challenges include releasing RNA from cells without damaging them, determining porous array density, and developing a sequencing method.
  3. Potential solutions include using electroporation or biological nanopores, adjusting array density, and utilizing real-time sequencing approaches.

All About The MiSeq

36 implied HN points • 04 Sep 23
🔬 Science Genomics Sequencing Technology
  1. The MiSeq is one of Illumina's longest read sequencers.
  2. Illumina released the MiSeq to compete with Ion Torrent sales.
  3. The MiSeq is the oldest next-gen sequencer in the market, released in 2011.

Is Oxford Nanopore Failing?

21 implied HN points • 11 Jan 24
💼 Business Finance Technology Growth Failure Market Analysis
  1. Oxford Nanopore has about 3.5 years of cash runway based on their current financial situation.
  2. The company received significant amounts of money outside of product sales which impacted their financial numbers.
  3. Oxford Nanopore's growth trajectory and accuracy claims may not align with their goals of surpassing Illumina in the market.

Thoughts On Pacific Biosciences

29 implied HN points • 14 Sep 23
🔬 Science Biosciences Sequencing Accuracy
  1. PacBio's raw accuracy has only slightly improved over 4 generations of instruments.
  2. Fundamental issues, like polymerase kinetics, may be limiting the accuracy of PacBio sequencing.
  3. PacBio has prioritized longer read lengths over accuracy, using cyclic consensus sequencing for improved results.

What's Going On At Oxford Nanopore?

14 implied HN points • 03 Mar 24
💼 Business Technology Finance News
  1. Several changes are happening at Oxford Nanopore, such as key members leaving the board and the company facing a possible firing of 1/3rd of the staff if revenue doesn't improve.
  2. The anti-takeover shares are set to expire soon, raising questions about the company's future.
  3. Oxford Nanopore's stock price has hit an all-time low, and their earnings report is expected next week, adding more uncertainty.

NextSeq 550 Flowcell Notes

14 implied HN points • 29 Feb 24
🔬 Science Research Instruments Materials Optics
  1. NextSeq 550 flowcell has a unique design where the gasket sits on the flowcell interface and the glass is thicker than other instruments, possibly for stability.
  2. The flowcell glass thickness is surprising and might impact the imaging process, requiring specific optics designed for it.
  3. The material of the channel spacer in the flowcell is unknown, leading to curiosity about its composition and potential patent research.

Ultima Unpatterned Flowcells

14 implied HN points • 14 Feb 24
🔬 Science Biotechnology Genomics Technology Research Innovation
  1. Ultima has transitioned to using unpatterned flowcells, which are cheaper and possibly work well with minor drawbacks.
  2. Ultima's manufacturing using unpatterned flowcells involves surface treatment and spin coating to attach and shrink beads for better identification and access.
  3. The occupancy and loading efficiency of Ultima's unpatterned flowcells suggest a potential capacity for 8 billion reads per run, showing advancements since their 2022 preprints.