Article from GENOMEWEB

SPOC Proteomics Aims to Boost Throughput, Lower Cost of SPR Protein Assays

Feb 29, 2024 | Adam Bonislawski

NEW YORK – With the recent introduction of its protein biosensor chips, SPOC Proteomics is looking to dramatically reduce the cost and boost the throughput of surface plasmon resonance (SPR)-based protein binding assays.

A spinoff from DNA nanopore sequencing firm INanoBio, itself a spinout from Arizona State University, SPOC (for Sensor-Integrated Proteome On Chip) aims to leverage its in situ cell-free protein expression system to develop inexpensive, highly multiplexed arrays of full-length folded proteins for protein binding experiments read out via SPR.

The company plans to target pharma research but believes the technology could also prove useful for diagnostics in areas like infectious disease, said Bharath Takulapalli, SPOC’s founder and CEO.

SPR has been a commonly used tool for pharma research for decades. One of its main advantages is that it provides data not only on whether a protein binds a particular target but on the kinetics of that binding.

“Not many folks, even in proteomics, talk about kinetics,” Takulapalli said. “But my personal view is that 50 percent of protein function is encoded in the kinetics, the binding strength — on/off rates and so on.”

He offered the example of the many SARS-CoV-2 strains that emerged over the course of the COVID-19 pandemic and the variation in their behavior.

“It’s the same set of 25 or 26 viral proteins, almost always impacting the same set of human proteins,” he said. “How come there is this huge variation in pathogenicity? I believe part of the answer is in the kinetics, changes to the strength of the binding [between host and viral proteins] and how that changes the mechanisms of disease.”

SPR has historically been a relatively low-throughput tool, however, with experiments typically limited to fewer than 10 protein targets. Additionally, the purified proteins required for such experiments are expensive, costing in the hundreds of dollars.

“If you need to outsource, say, 100 different proteins for an assay, you are looking at $25,000 to $50,000 just to get them into the lab, minimum,” Takulapalli said. “And that doesn’t include the spotting and screening them on SPR itself.”

SPOC is using an in situ protein expression approach that Takulapalli and his colleagues developed during his time as a postdoc and then research scientist at ASU’s Biodesign Institute. Using this method, the company is able to quickly print arrays of proteins made from plasmid DNA directly onto SPR chips. In a BioRxiv preprint published last month, Takulapalli and SPOC researchers including Chief Operating Officer and Cofounder Mukilan Mohan wrote that using the approach, they can create chips containing up to 2,400 unique full-length folded proteins at a cost between tenfold and 100-fold less than conventional methods.

SPOC announced at the Society for Laboratory Automation and Screening annual meeting in February that it was making its chips available for beta testing. Takulapalli noted, however, that the chips are not currently compatible with any SPR readers on the market. The company is working with high-throughput SPR instrument vendor Carterra, though, to be able to read out its chips. It is using a customized Carterra instrument for its internal work.

SPOC aims to launch two to three pilot studies this year with biopharma companies, Mohan said, positioning the platform as a tool for preclinical drug discovery.

Meanwhile, the company is working to develop a catalog of chips for specific research areas like neurodegeneration and various types of cancer.

The goal is “to have all these panels available for purchase early next year once compatibility with commercial instruments exists,” Takulapalli said.

Chris Silva, VP of marketing and product at Carterra, said that his company’s platform is capable of reading SPR chips with up to 384 spots.

“What SPOC wants to do is really broaden that number and enable even higher throughput, and that is what we are collaborating on,” he said.

Silva said the collaboration could help Carterra move into new applications spaces and new markets.

“I think SPOC is developing something targeted more to clinical and translational research, and we have really focused in the [drug] discovery space,” he said. “So there’s great synergy for us to work with them, because we are focusing on different aspects of the drug development workflow.”

“The demand for understanding [protein] expression profiles in serum and blood samples is increasingly important to understanding disease, and so it will absolutely be very enabling for the research and clinical translational research communities to have this capability,” he added.

Longer term, Takulapalli said SPOC aims to make its chips compatible with SPR instruments from a variety of companies.

He said a core application the company plans to target is drug candidate screening — both biologics and small molecules — as part of AI-based drug development processes.

“When companies develop AI-designed molecules, they almost always end up with hundreds to thousands of [candidates],” he said. “We could help generate the kinetic data [on binding of those molecules to their protein target] that they could then feed back into their models and develop an iteratively improved molecule.”

The platform could also be useful for assessing off-target effects, Takulapalli said, particularly in the case of short-lived binding events, which he said existing high-throughput methods often have difficulty detecting.

Brunner Cyrill, an application specialist at Bruker, which recently launched a new 64-plex SPR instrument, the Triceratops SPR #64, noted that SPR is a useful technology for evaluating findings from proteomics experiments.

“When you do proteomics to identify potential targets that you need to validate, SPR is a good orthogonal technology, because you get access to affinities, you get access to time resolution,” he said.

He noted that the move to higher levels of plexing makes SPR a better fit with mass spec-based proteomic workflows.

“You get from proteomics with mass spec 30, 70, 100 proteins in a run that could be potential biomarkers for a disease, and then you need a technology that is able to cope with that many proteins in a reasonable fashion.”

Higher multiplexing also makes for a more efficient screening process, particularly in therapeutic fields like oncology “where you often have to deal with mutant versions of a protein [target],” Cyrill said.

“It makes sense to include those mutants in your screening to try to identify as early as possible structures that are either specific [to a single protein] or target multiple proteins,” he said.

Takulapalli said SPOC plans to pursue diagnostic applications for its technology, as well. He suggested, for instance, that it could develop chips featuring antigenic proteins from a wide variety of pathogens that could be used for diagnosing infections.

“If there is a confounding symptomology, we could screen [the chip] against a serum sample and look at the antibody responses and complement that with [nucleic acid] approaches,” he said.

Takulapalli said that INanoBio and SPOC Proteomics have, combined, raised roughly $19 million from angel investors and received $7.5 million in federal grants, which was used to fund development of both INanoBio’s sequencing technology and the SPOC platform. Takulapalli and Mohan remain CEO and chief operating officer, respectively, of INanoBio. Takulapalli said SPOC is targeting around $25 million in a Series A funding round it plans to close in Q2 of this year.


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