NPN Clogging with Particle Size and Concentration (FOW)

This figure appears in our 2016 JMS paper and describes the clogging behavior of NPN with a 37 nm average pore size. The y-axis is the volume of filtrate after 1 min of forward centrifugation at 690g (3000 RPM). The x-axis is particle concentration in #/ml. The particles are polystyrene. Note we chose a size too large to fit through the membrane (100 nm) and particles (and protein) much smaller than the pores. Larger particles clog at much lower concentrations than small particles but the paper concludes that cake formation is the primary mechanism for clogging. The figure gives sound advice for the concentrations at which to use our membranes in this mode of filtration. Stock polystyrene (PS) concentrations in this figure are the far right data points of the 100 nm and 20 nm curves. So one needs to dilute PS NPs to work with them in dead end filtration. Gold is orders of magnitude less concentrated which is one reason it makes for a much better NP sample in our studies (the basis of all of our sieving curves for example).  The protein concentration ranges from 0.5 mg/ml to 5 mg/ml.

Lately I’ve been thinking about this figure with respect to nanoparticle (also virus, exosome) capture in a centrifuge. In this application we are interested in generating a clogging event but the clogging mechanism should be pore blocking (i.e. filling the pore as a plug). Interestingly, we didn’t see this mechanism in the JMS paper but it seems it would require a careful tuning of particle size and concentration. The particles should be around 40 – 50 nm to be captured inside tapered pores and the concentration should be tuned to the match the number of pores. With roughly 10 x 10^10 pores/cm^2 and a 0.036 cm^2 for our newest (4 slot SepCon) membranes, we can theoretically capture 3.6 billion particles. Lets say we start with a 200 ul sample and spin 100 ul through the membrane, the sample could theoretically be as concentration as 3.6 x 10^10 /ml NPs to reach saturation. Dropping to 10% of this number seems safer, so 3.6 x 10^9 /ml.  Interpolating from the figure above to an imaginary 40 nm particle at this concentration, we should expect a pretty good flow rate (100 ul/min) for a quick capture process.

About

Professor McGrath holds a BS degree in Mechanical Engineering from Arizona State and a MS degree in Mechanical Engineering from MIT. He earned a PhD in Biological Engineering from Harvard/MIT's Division of Health Sciences and Technology. He then trained as a Distinguished Post-doctoral Fellow in the Department of Biomedical Engineering at the Johns Hopkins University. Professor McGrath has been on the Biomedical Engineering faculty at the University of Rochester since 2001 where he also served as the director of the graduate program in BME for more than a decade and currently serves as Associate Director of the URNano microfab and metrology core. Professor McGrath also has faculty affiliations with many other programs at UR including the Material Research Program, the Environmental Health and Sciences Center, the Biochemistry and Biophysics program, and the Musculoskeletal Research Center. McGrath's graduate, post-doctoral, and early faculty research was focused on quantitative experiments and mathematical modeling of cell migration covering molecular, cellular, and multi-cellular phenomena. This was true until 2007 when he, along with Professor Philippe Fauchet (now Dean at Vanderbilt) and PhD students Tom Gaborski (RIT) and Chris Streimer (Adarza), discovered a means to self-assembled nanopores in 15 nm thick free-standing silicon and demonstrated the remarkable transport properties of the new material in a Nature paper. This seminal discovery led to the creation of the multidisciplinary Nanomembrane Research Group (NRG) and the founding of SiMPore Inc. in the same year. The NRG and SiMPore have been dedicated to the advancement of ultrathin membrane technologies and exploring all of their potential applications ever since. This blog also dates back to 2007 and has had contributions from more than 100 students, faculty, scientists, engineers, and entrepreneurs. It contains over 2,500 pages and posts logging progress large and small over all these years. Yet somehow it feels like we are just getting started.

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