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

A Q&A With... Me.

72 implied HN points • 26 Feb 24
🎙 Podcasts
  1. The post is a Q&A session with Nava Whiteford, shared on Substack, a platform for paid subscribers.
  2. Nava was asked to participate in a Q&A for a conference, but it's uncertain when or how it will be published.
  3. The post is exclusive for paid subscribers, and interested individuals can subscribe on Substack to access it.

Nanostring Vendors

51 implied HN points • 05 Mar 24
💼 Business Bankruptcy Instruments
  1. The post discusses Nanostring creditors identified in bankruptcy proceedings, indicating a Google document with detailed creditor breakdowns and mentions suppliers of 'Compelling presentations for litigation'.
  2. The focus of interest lies in the technical components used in Nanostring instruments, narrowing down the list significantly.
  3. Access to the full post is restricted to paid subscribers.

Those 10X Patents

51 implied HN points • 24 Feb 24
🕹 Technology Patents Lawsuits Enforcement Imaging
  1. 10X Genomics has been involved in several lawsuits related to their patents in the spatial space, with most patents set to expire around April 2031.
  2. There is one patent that expires in 2036, which seems to be focused on imaging systems.
  3. If 10X Genomics continues to enforce their patents effectively, they could maintain dominance in the spatial market for the next 7 years.

Some Atto-532 In A MiSeq

51 implied HN points • 15 Feb 24
🔬 Science Imaging Research
  1. The post discusses experimenting with Atto-532 in a MiSeq for epi-fluorescent microscopy, highlighting the process of preparing and imaging on a microscope slide.
  2. Images taken show varying brightness in different color channels, with Atto-532 matching well with the green LED used in MiSeq technology.
  3. There's an anticipation of potential dye crosstalk, with the expectation of leakage from the G dye into the T channel, suggesting Atto-532 as a good match for the G dye.
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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.

Oxford Nanopore - Baseless Rumors

36 implied HN points • 24 Feb 24
🕹 Technology Rumors Layoffs Strategy Management Technology
  1. Rumors about layoffs and nepotism at Oxford Nanopore are circulating, potentially impacting the company's share price.
  2. The company's delayed announcement of layoffs raises questions, with some seeing it as a strategic move and others as a demotivational tactic for employees.
  3. The overall strategy of Oxford Nanopore is being called into question, with suggestions that changes may be needed for the company to succeed.

Some Notes On the MiSeq Flowcell

29 implied HN points • 27 Feb 24
🔬 Science Instruments Construction Materials 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.

Ultima Genomics - More Reads Per Bead?

36 implied HN points • 20 Feb 24
🔬 Science
  1. In DNA sequencing, methods that ensure one bead and one template per droplet can significantly increase throughput.
  2. Ultima Genomics has been working on a method that allows 100% of beads to have product from a single template, potentially doubling throughput.
  3. Ultima's approach shows promise in reducing polyclonal rates, potentially offering an advantage over existing platforms.

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.

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.

4 Reads Per Cluster! Simultaneously Paired End-Sequencing!

36 implied HN points • 31 Jan 24
🔬 Science Genetics Bioinformatics Sequencing Biotechnology
  1. Illumina has a method to potentially double their instruments' throughput, but it may come with a slight decrease in accuracy.
  2. By simultaneously reading both the forward and reverse strands, Illumina can achieve four reads per cluster, doubling the throughput.
  3. Implementing the simultaneous paired-end sequencing approach may be challenging without sacrificing accuracy, but it opens up opportunities for increased throughput in the future.

PacBio Market Cap <$1B

7 implied HN points • 18 Mar 24
🕹 Technology Market Analysis Genomics Competitors Sequencing
  1. PacBio's market cap drops below $1B, making it potentially attractive for acquisition.
  2. Despite some positives like new instruments and competitive specs, PacBio faces challenges in gaining traction for long-read sequencing in clinical settings.
  3. The majority of PacBio's IP expires in 2029, raising concerns that competitors could enter the market in the near future.

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.

Rationalizing The Illumina Instrument Lineup

51 implied HN points • 09 Jan 24
🕹 Technology Biotechnology Instruments
  1. Illumina has a variety of sequencing instruments in their lineup, which includes different models and variations.
  2. The cost of production for these instruments varies based on the technology and components used.
  3. Rationalizing the Illumina instrument lineup could involve withdrawing some current models and introducing new, more cost-effective options.

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.

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.

Sequencing In Oncology

36 implied HN points • 23 Jan 24
🏥 Health & Wellness
  1. Clinical sequencing market is surpassing research in sequencing.
  2. Oncology is the largest clinical market, with a significant revenue.
  3. Companies like Exact Sciences are prominent players in precision oncology testing.

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

7 implied HN points • 14 Mar 24
🔬 Science Genomics Biology Technology Business Analysis
  1. The misconception that the author is independently wealthy is addressed, highlighting the need for funding for their content creation activities.
  2. The discussion covers the vertical integration strategies of AffyMetrix and Illumina in the genomics industry.
  3. There is a desire for a less vertically integrated future in the sequencing industry, focusing on filling sequencers with reagents like qPCR machines.

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.

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.

Maybe Nanopore Protein Sequencing Is Easier Than I Thought?... Maybe Not?...

7 implied HN points • 12 Mar 24
🔬 Science Sequencing
  1. Protein sequencing can potentially be easier than expected with nanopore technology, allowing for detection of PTMs and obtaining unique fingerprints from proteins.
  2. Proteomics differs from DNA sequencing in that it allows for estimating protein abundance and identifying PTMs in samples, possibly through aligning multiple protein traces.
  3. Challenges in proteomics applications with nanopore platforms include achieving the necessary dynamic range for accurate measurements, which may require advancements in technology.

Is The Revio A Single Color System?

7 implied HN points • 11 Mar 24
🔬 Science Research Technology Innovation Analysis Biology
  1. The Revio possibly uses a single color system for sequencing, which could lead to improved efficiency and simplification of the fabrication process.
  2. The SNR (signal-to-noise ratio) varies significantly between nucleotides in the Revio, indicating potential differences in brightness.
  3. There is ongoing exploration to determine if the Revio sequencing system utilizes a one or two-color system, with a focus on experimental support and additional evidence.

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.

Destroying DNA Sequencers

7 implied HN points • 10 Mar 24
🕹 Technology Security Software Auditing
  1. DNA sequencers can have security vulnerabilities that can be exploited, potentially causing physical damage to the instrument.
  2. Access to the fluidics system in a DNA sequencer could allow for sabotage by manipulating reagents to cause damage.
  3. Careful manipulation of lasers, filter wheels, and motion control components in a DNA sequencer could lead to costly damage, impacting the instrument's functionality.

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.

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.

The HiSeq X Flowcell

43 implied HN points • 18 Dec 23
🔬 Science Research Biotechnology Data Analysis
  1. About 30% of reagents may be wasted in dead volume on the HiSeq X Flowcell.
  2. The flowcell channels on the HiSeq X have a volume range of 15 to 20 uL.
  3. There could be significant cost implications if reagents costs are a large part of the sequencing expenses.

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.

The Future of Sequencing

29 implied HN points • 04 Jan 24
🔬 Science Genomics Automation
  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.

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.

Death And NanoString

14 implied HN points • 08 Feb 24
  1. Death can be understood in different categories like reversible/natural or irreversible/catastrophic.
  2. Chapter 11 bankruptcy involves a compromise between a debtor and creditors to reorganize a company.
  3. The concept of a 'forever company' raises questions about the necessity of companies dying for market evolution.

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.