The bestselling drugs are biologicals. For example, sales of AbbVie’s Humira were $18.4B in 2017. As of 2018, 75 mAb’s (monoclonal antibodies) have been approved. More are under development, which in addition to cancer and rheumatoid arthritis will also address Alzheimer’s disease and high cholesterol, expanding markets 10-fold. Not only biomolecules, such as mAb’s, but also viruses and whole cells are currently successfully used for gene and anti-tumor therapies, respectively. Emerging uses of viruses and exosomes to deliver drug payloads to specific targets promise more advances in therapies.

High manufacturing cost is the main impediment on the path of bringing biologicals to patients. Biologicals can be produced only by biotechnology routes, encountering multiple cost drivers and requiring multiple strategies to alleviate costs. Implementing continuous processing is one of the strategies that can decrease the initial investment 4-fold and the cost of generating biologicals at least 2-fold. Prevention of batch losses, which can lead to lost revenues in $10M-$1B range, is another strategy. A typical cause of loss is infection of the batch by viruses or mycoplasma that are difficult to detect because of their size and the presence of complex biobackground. The “cursed” size range of 10-100 nm is too large to use efficiently methods developed for biomolecules and too small for methods developed for cells. Similar to these bad actors, emerging drugs based on exosomes and viruses encounter separation challenges because of their size. Process scaling adds to the overall costs because many technologies involved in processing are not applicable both at small and large scales. The need to concentrate biologicals for the formulated product requires an extra step that adds to processing costs and, therefore, to product losses.

By employing our technology, the biotech industry can cut production costs by easier scaling up of processes, unification of the equipment, reduction in processing steps, and improved ability to handle particles in the size range of 10-100 nm. Because our separation platform is non-specific and can be applied to a wide range of sizes and volumes, it has application at every step spanning the biological’s development to its production. This gives access to a huge market of the biotech industry with a wide geographic footprint. The ability to satisfy various requirements eases both the initial penetration and further expansion through various customer segments.

We are building a platform of smart materials. More specifically, we are using shape-memory materials that switch between two structures at nanoscale in a process controlled by an operator. We shape biocompatible polymers to provide rigidity to the matrix and to accelerate transitions. For simplicity, the first generation will use temperature to change the shape. Such “through-wall” control enables straightforward coupling between a control block and disposable cartridges that can be sealed for sterility. Fractions can be separated with minimal dilution or even concentrated during the process. Avoiding compression against rigid surfaces keeps intact even the most delicate of the particles throughout the process.

The platform core is specifically sculptured matrix of shape-memory material. It can be applied to different uses by changing the configuration of component packaging. The package includes the controls for matrix transformation as well as accessories required to execute the application (e.g., sample injection, flow control, etc.). These systems can be optimized in wide range of processing liquid volumes (between 10 µL and 1,000 L) and of target sizes (between 1 nm and 100 µm). The volume defines the application field: from analytics, detection, and diagnostics in small volumes to manufacturing therapeutic biologicals in large volumes. The size range incorporates all biological targets beginning from biomolecules, exosomes, viruses, microvesicles and up to bacterial and eukaryotic cells.

We have developed a sensitive optical system to control and monitor the structural transformation of the shape-memory materials. Using the system, we prototyped a surface-immobilized matrix that transforms at physiological temperature. The prototype matrix was able to quantitatively separate protein molecules from cell-size particles. While the technology we develop is novel, it is based on known effects and chemistries; no fundamental discoveries are needed.

We develop two systems; each comprises two core elements – a permanent control unit and a disposable cartridge. Our small-scale Analytical System can be used in R&D and in quality control, targeting laboratories and production facilities in academia and industry. The large-scale Continuous Processing System is primarily intended for industrial manufacturing. Both systems are capable of using cartridges with different performance parameters to address customer needs. While cartridges evolve improving their performance, they still can be used with the same control units.