Millennial Scientific has been awarded a competitive Small Business Innovation Research (SBIR) Phase II grant from the National Center for Complementary and Integrative Health (NCCIH) National Institutes of Health (NIH). The grant will allow Millennial Scientific to develop and commercially deploy electrochemically modulated chromatography media for the selective removal of nuisance compounds during plant-based natural product processing.
Natural products are a rich source of compounds for drug discovery. Analysis of the US Food and Drug Administration (FDA) drug registry of the past thirty years shows that the origins of approximately 34% of medicines could be traced back to natural products or their direct derivatives. Despite this history of success, natural product samples are grossly underutilized for high throughput screening. A significant challenge for high throughput bioassay screening natural products against molecular targets is isolating a bioactive compound mixture free from interfering nuisance compounds. Common classes of nuisance compounds include tannins, phorbol esters, anionic (sulfated) polysaccharides and sterols, and saponins.
Electrochemically modulated liquid chromatography has been explored to manipulate the electrically conductive stationary phase material's interfacial properties (e.g., surface charge and oxidation state) by applying a voltage and tweaking it. This capability theoretically allows the stationary phase's composition to be tuned before or during the separation procedure and, thus, manipulates the interactions between the stationary phase and analytes. Various academic laboratories have investigated this technique for liquid chromatography using stationary phases comprising metal particles, synthetic graphite particles, or conductive polymer-coated inorganic particles. However, this technique has not been assessed for pre-liquid chromatography sample preparation using solid-phase extraction procedures. Further, sample preparation and chromatography products that exploit this mechanism are unavailable.
The products developed from this grant exploit the carbon microbeads' electrical properties to facilitate superior extraction and isolation of nuisance compounds called tannins in plant-based natural product extracts. Its electrically conductive surface allows manipulation of interfacial properties (e.g., surface charge and oxidation state) to attract or repel permanent or transient charges of compounds. Simultaneously its chemical composition enables non-covalent interactions due to pi bond stacking between aromatic rings of analyte and pi bond network on carbon nanomaterials. The understanding gained will also allow the development of methods for the selective removal of other nuisance compounds from natural product extracts. This grant will provide $1.5 million over 2 years.
"The grant will allow Millennial Scientific to leverage the capability of its patented materials and fabrication technologies to customize composition, structure, and function." Said Balaji Sitharaman, Ph.D. president. "According to NCCIH, Natural products are a source of diverse biologically active components. However, methods to identify bioactive natural products and their pharmacological mechanism(s) are often suboptimal or take too much time to be interfaced with modern screening platforms. NCCIH's current strategic initiatives focus on advancing the natural products research capabilities and removing bottlenecks stanching further exploration in the field."
The Phase II project's overall goal is to finalize the electrochemically controlled NanoPak-C cartridge product to allow its commercial launch. The substrates will be coated with electrically-conducting all-carbon spherical microparticles synthesized using natural micro-graphite. This substrate is a customized extraction unit that will facilitate the selective removal of tannins from plant extracts under an applied low electric field. The proposed technology will attract customers whose analysis requirements fall outside the capabilities of current solid-phase extraction materials and those seeking faster, more efficient analysis at a lower cost and with decreased reagents and consumable usage. It will also attract customers seeking next-generation performance capabilities to remove nuisance compounds from natural product extracts.