NEW YORK (GenomeWeb) – Michigan startup Akadeum plans to enter the life science industry with its microbubble technology to help researchers identify and isolate circulating tumor cells (CTCs) and other molecules.
Earlier this month, the Ann Arbor-based company demonstrated at the American Association for Cancer Research annual meeting how microbubbles can help to deplete red blood cells (RBCs) from liquid biopsies.
Founded by CEO Brandon McNaughton and CTO John Younger in 2014, the firm is built on next-generation separation technology to collect rare cells or molecules for different types of analyses, including CTCs from liquid biopsies.
Traditional tumor tissue biopsies are often painful, risky, expensive, and limited by the difficulty of accessing the tumor site. Therefore, prognostic biomarkers from liquid biopsies, such as CTCs, have motivated researchers to develop new techniques. However, isolating and collecting CTCs can be challenging for many reasons, including the presence of large numbers of white or red blood cells.
Younger noted that standard CTC collection involves bulk methods, including centrifugation, where researchers deplete the majority of cells, leaving tumor cells behind. Other brute force methods, involving microfluidics, examine every cell to search for the desired cell type.
In stark contrast to these methods, Younger explained, Akadeum's technology uses low-density glass-shelled, air-filled bubbles to "clear the field of everything else that the user doesn't want to examine." His team functionalizes the bubbles' surface with antibodies to any number of cellular targets. The bubbles then bind to the target and float it to the surface.
"The method acts like a biological lock and key," McNaughton explained. "If you're looking for a human T-cell, [we] can use an antibody that specifically grabs the T-cell." The overall protocol requires anywhere between 10 and 45 minutes, depending on the type of cell and exact workflow the researchers choose to follow.
According to Younger, Akadeum's microbubble technology can isolate cells in a variety of liquid and tissue biopsies. He noted that clinical users primarily examine peripheral blood samples, while researchers can use the technology for blood, spleen, and bone marrow samples derived from cell suspension culture. He explained that microbubble technology "allows for a lot of flexibility in not only what the bubbles can recognize, but also what they start with, as well."
According to McNaughton, the firm initially encountered challenges solving some of the nuances of microbubbles in order to perfect the CTC capture technology. Most of the issues stemmed from adding specific qualities to the bubbles that would work with the requirements of different sample types.
"It took a couple of years to figure out the right size, density, surface chemistry of the microbubble," McNaughton said.
Akadeum has applied for four patents related to its technology. Younger said that one of the patents centers on the idea of combining microbubbles with magnetic separation, while the other three focus on microbubble manufacturing, microbubble manipulation and sample extraction using disposable microbubble separators, and specific applications, including the use of large and small volumes.
The firm has not performed any of its own clinical studies, but it has partnered with academic collaborators to test upcoming products. For example, Akadeum recently presented research with the University of Michigan and University of South Alabama Mitchell Cancer Institute ona planned red blood cell microbubble product at the AACR meeting.
McNaughton highlighted that researchers will be able to use the RBC microbubble tool, which will be for research use only, to clear away red blood cells and leave behind rare cancer cells. With a price tag of $200 per kit, the process only takes 10 minutes and can reduce the time required for fluorescence-activated cell sorting by 36 percent.
"That means [there is] less time that the user is sitting in front of the instrument, [and] less time that their cells are waiting to be used," Younger explained. "Removing delays has been a frequent request by users, so that they can move on with their [research] and not the sorting."
Akadeum is also performing a closed beta testing program for three other upcoming products — Mouse B Cell, Mouse T Cell, and Human T Cell enrichment kits — with a number of research groups. The firm plans to launch the three products after completing the program, probably in the fourth quarter.
"As soon as we are done with the closed beta program, that's when we anticipate the launch and commercial availability of the three remaining products," McNaughton said. "All three will have slightly different list prices, but when they release, they will be price-competitive to the market."
Akadeum is currently exploring another financing round before the end of 2018, as the majority of its current financing stems from angel investors and venture capital investors. Last September, the firm raised $1.5 million in a financing round that was led by Silicon Valley-based Inflexion Point Partners. ELab Ventures and Agilent Technologies have also invested in the company since its start in 2014.
In addition to offering products for cell separation, Akadeum aims to enter the DNA and protein separation market, as well as the food pathogen detection sector. For food pathogen detection in particular, investors and partners are interested in working with the firm on potential diagnostic products, McNaughton noted.
"Again, we are a startup, and will explore further options when it makes sense to pursue strategic partnerships with companies in particular markets," Younger said.
In an email, Seungpyo Hong, a professor at the University of Wisconsin School of Medicine and Public Health, said he believes that the firm's microbubble technology has potential to replace the centrifugation step in cell analysis and will be effective when integrated with other CTC detection methods that are more specific.
Because Akadeum's sample preparation methods are not specific to CTCs, however, they may not be able to achieve highly specific capture of CTCs, he said. Most of the standard CTC separation techniques apply density gradient centrifugation to blood and use the "buffy coat" fraction that contain white blood cells, platelets, and CTCs. Hong then emphasized that it is a challenge to "specifically detect CTCs out of the buffy coat."
In addition, Akadeum is not the only player in a crowded yet rapidly growing market for CTC separation. Hong, who is also the CEO of Capio BioSciences, for example, explained that his firm's CapioCyte technology uses a combination of cell rolling and multivalent binding mediated by surface-immobilized nanoparticles to capture CTCs, using CTC-specific antibodies.
In the next two to three years, Akadeum aims to deploy its products across the US and possibly abroad.
"The idea is that when [researchers] use the equipment that they've spent a lot of money on, including their microfluidic flow analyzer and cytometric sorter, they have the material they want to work with, instead of the extraneous material," Younger explained.