Skip to main content
Premium Trial:

Request an Annual Quote

Vendors Assess Exposure to New US Export Controls on Mass Specs for Top-Down Proteomics

Premium

NEW YORK – The US Department of Commerce's release last week of an interim final rule (IFR) placing export controls on liquid chromatography (LC-MS) instruments "specially designed for top-down proteomics" has industry stakeholders working to assess the decision's impact and what instruments may be affected.

Several mass spec vendors in the space have indicated they do not believe the IFR will apply to their products, but exactly how the government will determine if an LCMS instrument is "specially designed for top-down proteomics" remains unclear.

Top-down proteomics refers to the mass spec analysis of intact proteins. It is a considerably smaller field than bottom-up proteomics, in which proteins are digested into smaller peptides before mass spec analysis. According to the Department of Commerce's Bureau of Industry and Security (BIS), which issued the IFR, "evidence suggests certain countries" are using LC-MS instruments designed for top-down proteomics to develop an "asymmetric military advantage."

The IFR notes that the instruments covered by the controls can be "used for research and development of concern to US national security," including the development of "human performance enhancement, brain-machine interfaces, biologically inspired synthetic materials, and possibly biological weapons."

Under the rule, companies selling these instruments abroad must obtain export licenses from the department before selling to any country outside the roughly 40 nations (excluding Russia, Malta, and Ukraine) participating in the Wassenaar Arrangement, an international export control agreement. For roughly 40 countries, there will be a "presumption of denial" of export licenses, while for all other countries, issuance of a license will be decided on a "case-by-case" basis.

Most significant from a vendor perspective is the IFR's potential impact on sales to China, which now falls under the "presumption of denial." China is a major market for life science tools and is highly active in proteomics research. In 2023, the Chinese government announced the launch of its π-HuB Consortium, or Proteomics Navigator of the Human Body, a 30-year, multibillion RMB effort that aims to map the human proteome. As of October 2023, the consortium had purchased 17 mass spectrometers, mainly from Thermo Fisher Scientific and Bruker, for a pilot lab in Guangzhou. Tiannan Guo, a tenured associate professor at China's Westlake University and a π-HuB participant, said at that time that it planned to purchase additional mass specs beyond those 17, likely Thermo Fisher Orbitrap Astrals and Bruker TimsTOF systems.

Applying for the export licenses required by the IFR "is not particularly complicated," said Adam Munitz, co-chair of the international trade practice at law firm Fluet, which focuses on the defense and security sectors, though he noted that processing these applications takes an average of around 45 days and that timeline can be extended depending on geopolitical events.

"Exporters and manufacturers need to build that flexibility into their contracts and sales orders," he said.

The IFR does not specify what LC-MS instruments fall under the new controls, and BIS did not respond to questions about what instruments will qualify as "specially designed for top-down proteomics."

While a variety of LC-MS systems are capable of performing top-down proteomics mass spec experiments, few are targeted specifically to top-down research as this is a small slice of the overall proteomics market. A 2023 study by the Consortium for Top-Down Proteomics comparing protocols for top-down proteomics across 11 laboratories gives a flavor of the instruments used for such work. The instruments used in the study were the Waters Synapt and Synapt G2-Si, the Thermo Fisher Orbitrap Q Exactive UHMR and LTQ Orbitrap XL, the Bruker Solarix FTICR, and the Agilent 6545XT SLIM QTOF.

These are mostly older instruments, some of which are no longer available for purchase. The most prominent LC-MS releases for proteomics research in recent years, including Thermo Fisher's Orbitrap Astral, Bruker's TimsTOF, and Sciex's ZenoTOF, have targeted the bottom-up proteomics market.

Reflecting this, most mass spec vendors in the proteomics space have said they believe they have little to no exposure to the IFR.

Bruker does not "currently have any products specifically designed for top-down proteomics," Joe Kostka, the company's director of investor relations, said via email, noting that all of the company's TimsTOFs are intended for bottom-up proteomics.

In a note to investors following the release of the IFR, Wolfe Research analyst Doug Schenkel included comments from Danaher (parent company of Sciex), Agilent, and Waters, all of which said they did not have meaningful exposure to the top-down proteomics market.

Thermo Fisher declined to comment on how the IFR might impact its business.

Thermo Fisher is one of the few firms to have recently released an LC-MS instrument clearly targeted to top-down research. At the 2024 American Society for Mass Spectrometry annual meeting in June, the company launched its Orbitrap Ascend Structural Biology Edition Tribrid instrument, which is intended for intact and native protein analysis.

Another Thermo Fisher system that could fall under the IFR is its Q Exactive UHMR (Ultra-High Mass Range) system, which is meant for native protein mass spec and top-down research. Thermo Fisher launched the Q Exactive UHMR in 2018, and in 2022 it added to the system what it calls its "direct mass technology," which gives it charge detection mass spec (CDMS) capability. Charge detection mass spec allows for high-resolution analysis of large molecules and complexes like intact proteins, antibody-based drugs, and protein complexes.

Waters also has CDMS technology, which it acquired via its 2022 purchase of technology and intellectual property from Megadalton Solutions.

In a recent note to investors, TD Cowen analyst Dan Brennan wrote that a KOL the bank spoke with suggested that instruments with CDMS capability are a likely target of the IFR. The KOL said the government could be concerned that these instruments could allow China to profile intact viruses. The bank estimated, however, that for the mass spec vendors it covers, the IFR would impact less than 1 percent of revenues.

Northwestern University researcher Neil Kelleher, a top-down expert and founder of the Consortium for Top-Down Proteomics, cited the Orbitrap Ascend and Q Exactive UHMR as examples of instruments well suited to top-down research. He suggested, though, that the IFR might have been written with an eye toward future instrumentation as much as existing systems.

"If the Department of Commerce wants to get ahead of the game, this is a great example of a move that would position you as the market is developed," he said.

Beyond the question of whether particular LC-MS instruments qualify as "specially designed for top-down proteomics," there is the matter of where they and the components used to make them are produced.

Bruker's Kostka said that the company's understanding of the ruling is that it would apply to products produced outside the US by US companies only if those products were more than 25 percent composed of US-origin components. He noted that the company's TimsTOF instruments, which are exported from Europe to China, would not exceed that 25 percent threshold.

In the Wolfe Research note, Waters and Danaher likewise said they believe the IFR would not apply to their instruments as they are produced outside the US.

Munitz said that "if products are produced overseas and don't contain substantial American content, it is going to limit the Department of Commerce's jurisdiction over those products."

The IFR also imposes export controls on high-parameter (26 or more channels) and spectral flow cytometers and cell sorters. Companies including BD Biosciences, Thermo Fisher, and Agilent sell instruments that would fall into these categories.

The IFR took effect on Jan. 16. Public comments on the rule may be submitted for 60 days after that date.