Technology

Nexgenia’s stimuli-responsive “smart” polymers in action

 

 
Nexgenia’s technology is based on unique and proprietary families of stimuli-responsive “smart” polymers which change their state in response to small, discrete changes in their environment. The polymers, and molecules or particles bearing the polymers, can be freely soluble at one temperature, pH or salt concentration, and transition within seconds to macromolecular aggregates at another temperature, pH or salt concentration.  This is a unique property not seen with other molecules.  When these smart polymer reagents are attached to other chemicals / biologicals, they confer on those chemicals the same environmentally-responsive characteristics.

For example, antibodies “decorated” with just a few smart polymers can react with the same speed as “native” antibodies, but can then be converted to large macromolecular aggregates for easy separation and detection when desired. Another example is magnetic microbeads, which currently are used by many of the largest immunoassay manufacturers as a carrier for antibodies in order to provide ease of separation. Magnetic microbeads can be reduced to 1,000th their volume for faster reactions, “decorated” with Nexgenia’s smart polymers, and then be separated just as easily as the larger slower magnetic microbeads by a change in temperature, pH or light. Because the surface to volume ratio of Nexgenia’s magnetic nanoparticles is 100 fold greater than that of large magnetic microparticles, the smart polymer decorated nanoparticles can also carry 100 fold greater density of antibodies for higher assay sensitivity.

Application in Personalized Cancer Immunotherapies

The emerging field of personalized immunotherapies, such as CAR T-cell therapies, rely heavily on the ability to separate cells from a patient sample quickly and efficiently.  Today, most cellular separations are performed on magnetic beads of micron-plus dimensions.  While beads of this size are easily separable in a magnetic field, they have limited surface area for the loading of antibodies and have extremely limited diffusion rates, both of which lead to slow binding of targets and long assay times.  Nexgenia’s polymer-bearing nanoparticles enable antibodies to be utilized at much higher concentrations and to bind with targets much faster.  Following target binding, the nanoparticles can co-aggregate within seconds to large size for faster more complete separations leading to faster and more sensitive assays.  This offers particular advantages when separating cells with low surface biomarker density.

For some cell types, currently available commercial kits perform well. Some commercially available kits achieve >90% purity and viability when isolating cells from peripheral blood. However, these kits show poor performance with certain cell types. Some publications report recovery rates as low as ~11% and cell purity levels of ~80%. Many academic researchers develop custom nanoparticless for difficult-to-capture cells.  A very recent report of custom-designed nanoparticle for cell isolation showed only 57% capture efficiency and 87% cell viability, so there is room for significant advances in separation technology. The poor performance of nanoparticles for certain cell isolations may be due to low surface receptor expression levels, the relative scarcity of cells in samples, or a combination of both effects

Nexgenia’s stimuli-responsive nanoparticles are different from other nanoparticles and offer a distinct advantage because the separation does not rely on a multiplicity of nanoparticles binding to cells. Only 1 (or a few) of Nexgenia’s nanoparticles must bind to the cell surface, and then a stimulus will cause the co-aggregation that will build sufficient magnetic moment for cell isolation. In essence, the co-aggregation serves as a magnetic amplification step.

Nexgenia has established significant proofs of concept with its proprietary polymers and are in position to engage potential strategic partners in evaluation of these reagents for use in their products and processes.  While there are many strategies for constructing faster and more sensitive binding assays and cellular separations, Nexgenia’s polymers and polymer-bearing nanoparticles are a platform technology that offers potential benefits far exceeding technology currently on the market.  For instance, Nexgenia’s nanoparticles offer greater speed, higher recovery rates and greater purity levels than current technology.  Also, Nexgenia’s magnetic nanoparticles do not need special equipment to perform cell separation on different cell types (such as stronger magnets).  You can use the equipment you already have.  Finally, Nexgenia’s technology can make accessible a host of new targets not readily accessible by current technology.

Interested companies are encouraged to contact us at williams@nexgeniacorp.com