NEW YORK (GenomeWeb) – With its mass spec multinozzle emitter array technology in beta testing with several outside parties, biotech firm Newomics is planning a limited commercial launch of the device in the next several months.
The Emeryville, California-based company is currently testing its technology with Thermo Fisher Scientific as well as a leading biotech firm and academic research team, said Daojing Wang, the company's founder and president.
In addition, the company is working to develop a multinozzle emitter chip version of a drug binding assay it recently published in a study in ACS Chemical Biology that Wang said allows for proteoform-specific characterization of protein-drug binding. Moving that assay to the multinozzle emitter chip format could provide additional sensitivity and throughput, he said.
The MEA device consists of a series of multinozzle emitters arranged in a circular array on a silicon chip. The multiple emitters allow for higher-throughput experiments, as each emitter can be interfaced to a separate LC system allowing for rapid sequential or parallel mass spec analyses. The increase in nozzles provides an improvement in sensitivity proportional to the square root of the number of nozzles per emitter.
Launched in 2013 as a spinout from the Lawrence Berkeley National Laboratory – where Wang and his co-founder Pan Mao invented the MEA technology – Newomics was started to commercialize MEA. However, the company has also shown an interest in assay development, focusing in particular on applying its technology to top-down proteomics.
Published in December, the ACS Chemical Biology study used a Thermo Fisher Q Exactive Plus instrument as well as a Waters Corp Q-TOF API US instrument to characterize interactions between small molecule drugs and intact proteins, specifically, in this case, the botanical extract thymoquinone and the protein human serum albumin (HSA).
Notably, Wang said, the researchers set out to look at not just the patterns of binding between thymoquinone and the overall population of HSA but at the different binding properties of specific proteoforms of HSA. This allowed them to identify different binding patterns between forms of the proteins including native and ultimately identify the specific amino acid residue on HSA, cysteine34, responsible for binding thymoquinone.
The results, Wang suggested, indicate "that when we look at protein binding, rather than just looking at the mixture of proteoforms of a protein, we should really zoom in on particular proteoforms."
"There are so many post-translational modifications and possible splice forms for each protein," he added. "A lot of modifications may change the proteins' conformation and therefore may change the availability of the proteoform for binding."
The study did not use Newomics' multinozzle emitter technology, but Wang said the researchers have since developed a version of the assay that does use the device and that the company is in the process of preparing a publication detailing that work.
The company has previously described other top-down proteomics assay using the multinozzle emitter system. In 2014, it published a paper in the Journal of Proteome Research on an assay for monitoring patient blood sugar that used the device to measure glucose as well as the intact forms of glycated hemoglobin, glycated HSA, and glycated apolipoprotein A-I. That assay also measured intact cysteinylated HSA, S-nitrosylated HbA, and methionine-oxidized apoA-I to gauge oxidative stress and cardiovascular risk.
While the throughput and sensitivity improvements enabled by the multinozzle emitter system are also applicable to bottom-up proteomics work, Wang said the firm has chosen to focus on intact proteins in the belief that top-down proteomics has been underexplored in terms of its potential clinical applications.
Newomics has grown from two to eight fulltime employees in the last two years and is currently funded entirely through grants from the National Institutes of Health worth a total of roughly $7.5 million, Wang said.
It has six active NIH grants totaling about $3.2 million: a $349,999 grant from the National Institute on Aging for Alzheimer's disease biomarker research; a $299,999 grant from the National Institute of Allergy and Infectious Diseases for biomarkers of radiation injury; a $688,748 grant from the National Center for Complementary & Integrative Health for development of a screening platform for molecular targets of natural products; a $746,462 grant from the National Institute of Environmental Health Science for development of microfluidic chips for biomonitoring; another $750,000 NIEHS grant for development of stem cell-based assays for screening chemical toxicity; and a $341,623 grant from the National Institute of General Medical Sciences for a new electrospray device for top-down proteomics.