Abstract Natural products remain a rich source of compounds for drug discovery. However, a significant challenge for high throughput bioassay screening against molecular targets is the isolation of bioactive compound mixture free from interfering nuisance compounds. The well-established ubiquitous nuisance compounds in plant extracts are Tannins - polyphenolic plant metabolites. The solid-phase extraction (SPE) process is now gaining recognition as a method for rapid fractionation of crude plant extracts and employed to remove nuisance compounds as well as purify and concentrate analytes before introducing them into more expensive gas- or liquid- chromatography instrumentation. Our customer discovery interviews found that the challenges with current reverse phase materials in the removal of nuisance compounds during natural product extraction include unsuitable for more than single-use, pH (degrades at basic pH) and temperature (degrades at T > 60°C) restrictions, and suboptimal performance in the removal of nuisance compounds such as tannins. These technical issues affected (increased) the operational costs to manufacture the product and decreased margins. This SBIR Phase II proposal’s overall objective is to finalize an innovative solid phase extraction unit that incorporates electrically-conducting all-carbon spherical microparticles (40 µM diameter), synthesized using multi-walled carbon nanotubes (MWCNTs) as starting material. This material will, under an applied voltage, facilitate selective separation and detection of tannins. During Phase II, two aims will be pursued. Aim 1. Demonstrate that the all-carbon microbead synthesis and solid-phase extraction substrates are scalable. Aim 2. Establish consistent performance across the scaled-up microbead and substrate batches, and demonstrate (a) improved retention of tannins, (b) rapid detection of trapped tannins by electrospray mass spectrometry, and (c) reuse of the cartridge. Expected outcomes include 1) Finalization of the setup and conditions that will enable the large scale manufacturing of all-carbon solid-phase extraction system. 2) Identification of the critical synthesis process parameters (CPP) that affects tannin extraction performance reproducibility and has to be monitored and controlled to ensure the process produces the desired quality without batch variability. 3) Finalization of scientifically sound and appropriate test methods that can eventually be qualified/validated for batch release testing. The scientific outcomes from the Phase II activities will facilitate the commercial launch of this product as well as enable its application for the removal of other nuisance compounds. Upon complete development, NanoPak-C will attract customers seeking next-generation performance capabilities that fall outside the capabilities of current state-of-art for the removal of nuisance compounds during natural product extraction and advance separation of active drug candidates from the purif...