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Nodexus Eyes Oncology Applications With Cancer Stem Cell Isolation, Detection Platform


NEW YORK – Startup Nodexus is eyeing the cancer detection space as it launches a new project that combines its node-pore sensing single-cell isolation tool with multi-marker screening technology. 

With help from a $300,000 National Cancer Institute grant awarded last month, the Hayward, California-based firm hopes to tailor its NX One sample prep platform to isolate and detect cancer stem cells (CSCs) in urothelial carcinoma of the bladder (UCB). 

Working with Mohammad Hoque, a urology professor at Johns Hopkins School of Medicine, Nodexus aims to integrate NX One with label-free multi-marker screening to potentially develop and commercialize a platform to detect CSCs. 

Founded in 2014 by CEO Karthik Balakrishnan and Chief Strategy Officer Anand Kesavaraju as a spinout of the University of California, Berkeley, Nodexus has since both exclusively licensed and independently developed the NX One platform, which offers fluorescence detection and label-free screening. Balakrishnan explained that NX One isolates single cells for applications such as drug discovery, diagnostics, and cell line development.

Clinicians may diagnose UCB patients using methods such as urine cytology, MRIs, and cystoscopies. However, most patients are diagnosed with the disease via tissue biopsies only after exhibiting visible symptoms, which can lead to health complications in later stages. 

Hoque said that his lab therefore is attempting to understand cancer stem cell regulation and find expression pathways to improve UCB patient treatment. In a study published in Cancer Research in 2018, Hoque's team identified regulatory and proinflammatory pathways that they could alter in order to modify chemotherapy response and clinical management of UCB in both in vitro and in vivo models. After publishing the paper, Hoque said that Nodexus approached his lab to help determine an appropriate approach for UCB biomarker research.

Nodexus' patented sensing technology applies unique microfluidic geometries to provide distinct electrical detection signatures as cancer cells dissociated from a solid tumor or samples from liquid cancers travel through the microfluidic channels. Kesavaraju said that Nodexus' label-free technology then allows users to apply the specific signatures to discriminate one population from another without altering the total population in a sample.

"Using these signatures in the new tool, we aim to expand characterization of individual cells for a variety of parameters with a label-free approach and subsequently isolate ones that exhibit target signatures in a viable manner for downstream studies," Kesavaraju explained. 

Balakrishnan said that Nodexus will use the NCI grant funding to address challenges in CSC detection, including problems with characterizing specific CSCs, screening and targeting specific biomarkers, and developing panels that serve to "conclusively determine if a certain cell is a CSC." Taking it a step further, Nodexus wants to offer researchers the ability to access and isolate cells in a manner that keeps them alive and retains their viability for downstream studies. 

Balakrishnan also noted the platform will allow users to select what type of characterized population they want to isolate in a "walk-up" manner, without requiring any type of prior calibration process. 

"There's a lot of interest from both sides [of the partnership] for urothelial carcinoma," Balakrishnan said. "While not necessarily an acute cancer, urothelial carcinoma requires regular monitoring, which has been invasive and expensive with tissue biopsy." 

Because Nodexus designed the platform to be walk-up usable and affordable, Balakrishnan noted that his team required time to improve the "plug-and-play" nature of the tool's microfluidic cartridges. However, he argued that manufacturing is often a tremendous challenge for developers in the microfluidics space. 

"We have designed the system to not require any tuning or calibration by the end user, which is a first for the cell sorting industry," Balakrishnan said. "We have put a focus on ensuring we can provide affordable products that can be universally adopted."  

Balakrishnan said that Nodexus has raised most of its funding through undisclosed private venture capital firms and angel investors. In addition to the NCI grant, Nodexus received three Small Business Innovation Research grants from the US Department of Commerce, the US Department of Agriculture (totaling $500,000) to develop the Nx One platform for CSC research. 

While Balakrishnan said that NX One has shown functional and operational improvements within internal studies, he acknowledged that applying the technology to targeted bladder cancer CSC isolation "is a unique challenge in itself." Nx One users may face similar limitations as users of methods such as fluorescent activated cell sorting and CyTOF because of the heterogeneity and rarity of the target cells. 

While certain parts of Nodexus' initial node-pore sensing patents stem from the group's exclusively licensed IP portfolio from UC Berkeley, Balakrishnan highlighted that the integrated platform — which includes expanded detection capabilities, sorting, and isolation — as well as the channels and cartridges,  have been exclusively developed by the Nodexus team.

After completing the pilot project, Nodexus envisions applying the technology to a wider range of cancer-based applications, including personalized cancer therapies. If Nodexus's combined platform successfully isolates CSCs without labeling before symptoms occur, Hoque argued that researchers could better grasp a tumor's characteristics and potentially optimize therapies tailored to a specific patient, improving overall treatment in the long run.

"If we can understand and isolate CSCs without labeling them, we can precisely study the pathways that are active in those cells," Hoque explained. "It would help us to understand CSC heterogeneity in general, as well as get a [comprehensive] idea of the cancer's properties at the molecular level."