NEW YORK – Protein sequencing firm Quantum-Si announced last week plans to develop a platform capable of large-scale proteomics experiments.
Called Proteus, the planned system will ultimately enable the analysis of billions of peptides per experiment, Jeff Hawkins, Quantum-Si's president and CEO, said during the firm's investor day event held Nov. 20. He said the company aims to launch a version capable of analyzing around 50 million peptides per experiment in 2026.
Meanwhile, sales of the company's current protein sequencing platform, the Platinum, have lagged expectations. During a conference call following its Q3 2024 earnings, Hawkins said Quantum-Si missed its internal revenue targets for the quarter and is unlikely to reach its full-year 2024 revenue guidance of between $3.7 million and $4.2 million.
Last week, the company said in a filing with the US Securities and Exchange Commission that it is laying off roughly 23 percent of its 187-person workforce in order to "streamline and focus its overall corporate resources, as well as align required resources to focus on future product development objectives," including the Proteus platform.
And earlier this month, Quantum-Si reported it received a delisting notice from the Nasdaq market alerting it that it no longer met the minimum bid price requirement for listing as its stock had closed at below $1.00 per share for 30 consecutive business days.
The market responded favorably to the Proteus announcement, however, as the company's shares more than doubled following the investor day event, closing at $1.39 on Nov. 20 after closing at $.63 the day before.
Quantum-Si's Platinum sequencer uses readouts of amino acid-specific probes, or recognizers, via a semiconductor-based sensing device that measures the timing of emissions following the excitation of target molecules, enabling single-molecule sequencing of peptides, including posttranslational modifications.
The company launched sales of the instrument at the end of 2022, though it said in November 2023 that it was pulling back its commercialization efforts and operating in a "controlled commercial launch" until early 2024.
The Platinum's consumables consist of chips containing 2 million wells. The deposition of individual peptides in these single wells follows the Poisson distribution, which dictates how densely a chip can be populated while maintaining the one protein-per well distribution that enables single-molecule analysis. Based on Poisson distribution, around one-third of the wells are expected to contain a single-peptide molecule (with the other wells containing either no peptides or multiple peptides), meaning that the 2 million wells allow for around 600,000 single-molecule reads per chip. Given this relatively limited capacity, the Platinum is primarily intended for targeted proteomics experiments — in-depth studies of protein proteoforms, for example.
The planned Proteus instrument represents a shift toward discovery-style proteomic experiments. While the initial version of the platform will use consumables containing 80 million wells with single-molecule occupancy of the wells following Poisson distribution, the system could ultimately reach up to 10 billion wells per consumable, Quantum-Si Chief Technology Officer Todd Rearick said during a presentation at the company's investor day. He added that the company is exploring sample prep approaches that could enable super-Poisson distribution, wherein the majority of wells would be occupied by a single peptide. This, he said, would allow sequencing of complex samples on a scale comparable to that of shotgun mass spec proteomic experiments.
For the Proteus, Quantum-Si is moving away from the detection technology employed by the Platinum system, which uses semiconductor chips to measure the lifetime of light emissions of amino acid-specific probes, or recognizers. Instead, the company is adopting a more traditional optical approach, in which it will use cameras to detect binding of its recognizers based on color.
Hawkins said that by moving to a color-based approach, the company can benefit from technology development in areas like next-generation sequencing.
"You really get to take advantage of commercially available optical components and filters and cameras," he said, noting that to continue using lifetime measurements for detection would have required the development of new, higher-density lifetime measurement systems to handle the higher-density consumables required to achieve the 10 billion wells for which it is aiming.
This is a shift from the early days of Quantum-Si when Founder Jonathan Rothberg highlighted the company's lifetime-based detection approach as key to distinguishing between the 20 different amino acids that make up proteins as well as posttranslational modifications of interest.
"If you have a big machine and it weighs as much as a refrigerator and costs half a million dollars, you can differentiate four colors optically, and that is the basis of most sequencing machines," Rothberg told GenomeWeb shortly after Quantum-Si went public in 2021. "But it's hard to differentiate more [than four] colors, and so we change color into time."
Hawkins said that since then Quantum-Si has "made significant advances in sequencing chemistry and algorithms," including "methods to more effectively distinguish and support many dyes using lifetime-[based detection], and those improvements translate to using color, as well."
He added that "continued investment in high-performance optical systems for NGS has reduced the cost structure of optical approaches significantly."
While Quantum-Si expects to launch the initial 80 million-well version of the Proteus in 2026, the timeline for hitting billions of reads per experiment is hazier.
"Most of what stands in the way is you have to build the consumable and develop the instruments to be able to scan a much larger area," Hawkins said. Perhaps the biggest challenge, he said, will be in optimizing the chemistry components required to expand to billions of reads.
Hawkins declined to provide expected pricing for the Proteus system but said that while it will certainly cost more than the Platinum instrument, which sells for $85,000, he doesn't expect it will "go all the way up to like the $1 million mass spec level."
Quantum-Si announced last week deals with Planet Innovation, SkyWater Technology, and Nvidia for development work on the Proteus platform. Box Hill, Australia-based Planet Innovation will help develop and manufacture the new system, while Bloomington, Minnesota-based SkyWater Technology is developing consumables. The company's collaboration with San Jose, California-based chipmaker Nvidia is focused on improving data processing speeds to handle the increased data volume the company expects the Proteus to produce.
Quantum-Si is also developing a next-generation version of the Platinum instrument called the Platinum Pro that it plans to launch in the first half of 2025. This system will still run on the company's existing semiconductor technology but will offer certain new features customers have expressed interest in, Hawkins said.
One will be the ability to process data generated on the system locally. Currently, Platinum users must use Quantum-Si's cloud environment to process and analyze data generated on the platform. This has limited uptake of the platform by customers in environments like government or pharma who may have strict policies around keeping all data on-site, Hawkins said.
The Platinum Pro will also allow for more flexible workflows, with kits to facilitate labeling of samples and software designed for the development of custom applications. Hawkins said the new instrument will be more expensive than the existing Platinum system but not dramatically so.
During its investor day presentation, Quantum-Si also detailed new applications for the Platinum technology, including a new approach to detecting protein posttranslational modifications (PTMs) that uses antibodies or other affinity reagents for PTM detection instead of the company's recognizers. In this workflow, affinity reagents can be used to gather information on PTMs that can be combined with sequence information then generated by the instrument's standard workflow.
Quantum-Si provided an example of work it did with phosphorylated forms of the protein CDNF, in which it detected a particular phosphorylated CDNF peptide present at a ratio of less than one phosphorylated peptide in 1,000. The company said that the approach is also applicable to full-length proteins, which could allow researchers to profile different proteoforms of proteins of interest. To date, Platinum workflows have focused on bottom-up, peptide-level analyses.