Fc microparticles can modulate the physical extent and magnitude of complement activity

Holt, Brandon Alexander; Bellavia, Michael C.; Potter, Daniel; White, David W.; Stowell, Sean R.; Sulchek, Todd

doi:10.1039/c6bm00608f

Cited by 15 publications

(9 citation statements)

References 66 publications

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“…Additionally, silica microparticles, 0.96 µm in diameter (Bangs Laboratories, Fishers, IN), were coated in 5 nm chromium and 20 nm overlaying gold for functionalization as described by Tang and Holt, et al 33,34 . The particles were filtered in fixed backflush experiments to confirm that beads designed for immunoengineering experiments could be efficiently purified 35 .…”

Section: Membranesmentioning

confidence: 99%

Optimizing Flux Capacity of Dead-end Filtration Membranes by Controlling Flow with Pulse Width Modulated Periodic Backflush

Enten

Leipner

Bellavia

et al. 2020

Sci Rep

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Standard dead-end sample filtration is used to improve sample purity, but is limited as particle build-up fouls the filter, leading to reduced recovery. The fouling layer can be periodically cleared with backflush algorithms applied through a customized fluidic actuator using variable duty cycles, significantly improving particulate recovery percentage. We show a Pulse Width Modulation (PWM) process can periodically backflush the filter membrane to repeatedly interrupt cake formation and reintegrate the fouling layer into the sample, improving net permeate flux per unit volume of sample by partially restoring filter flux capacity. PWM flow for 2.19 um (targeted) and 7.32 um (untargeted) polystyrene microbeads produced 18-fold higher permeate concentration, higher recovery up to 68.5%, and an 8-fold enrichment increase, compared to a uniform flow. As the duty cycle approaches 50%, the recovery percentage monotonically increases after a critical threshold. Further, we developed and validated a mathematical model to determine that fast, small-volume backflush pulses near 50% duty cycle yield higher recovery by decreasing fouling associated with the cake layer. Optimized PWM flow was then used to purify custom particles for immune activation, achieving 3-fold higher recovery percentage and providing a new route to improve purification yields for diagnostic and cellular applications. Dead-end filtration using patterned microsieves, fiber meshwork, and membranes of various materials is a standard technique to isolate desired particles of various sizes and is often used in clinical and laboratory settings for therapeutic and diagnostic applications 1-4. Both biological and physical suspensions can be filtered to yield high purity and enrichment at a high throughput. Dead-end filters are especially susceptible to fouling, however, which leads to lower recovery percentage and yield as a direct result 2,5,6. Because a decreasing yield negatively impacts therapeutic quality 7-9 , clinical and industrial therapeutic manufacturing will frequently change or increase the surface area of the dead-end filter 10 , or switch to crossflow filtration modalities 11,12 , which further decreases the throughput and increases processing time. Membrane fouling is caused by pore blocking followed by cake layer formation, resulting in an exponential decay with time in the flux of permeating particulate 13-19. Membrane fouling also affects crossflow systems and, in this case, numerous studies were conducted to disrupt cake formation and reintegrate particulates into the bulk flow feed stream 11,12,20-25. For example, crossflow filtration can disrupt caking by implementing an oscillatory flow with a sinusoidal flow velocity or a pulsatile flow, consisting of a steady flow with oscillations superimposed 20. These studies examined the effects of numerous waveforms, including variations of sinusoids, saw tooth, and square waves 12,20,23. Oscillatory and pulsatile techniques showed improved clearance of the crossflow membranes, leading to an incre...

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Section: Membranesmentioning

confidence: 99%

Optimizing Flux Capacity of Dead-end Filtration Membranes by Controlling Flow with Pulse Width Modulated Periodic Backflush

Enten

Leipner

Bellavia

et al. 2020

Sci Rep

Self Cite

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“…They increase local vascular permeability and cause vasodilation. The membrane attack complex also causes cell lysis [ 15 - 17 ].…”

Section: Reviewmentioning

confidence: 99%

Pathogenesis of Drug Induced Non-Allergic Angioedema: A Review of Unusual Etiologies

Kalambay¹,

Ghazanfar²,

Pena³

et al. 2017

Cureus

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Angioedema is the swelling of mucosal and sub-mucosal tissue. Typically, it manifests as the swelling of the face, lips, and tongue. Angioedema can be severe and life threatening when it involves the respiratory tract. Drug induced allergic angioedema and drug induced non-allergic angioedema differ in their mediator, their clinical presentations, and their management. In drug induced non-allergic angioedema, symptoms are resistant to antihistamine and corticosteroid treatment. The aim of the analysis was to identify which medications are associated with drug-induced non-allergic angioedema and to understand the mechanism of action via which of these medication cause angioedema.

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“…1, step 1). However, finding substrates with high specificity becomes increasingly difficult as the number of target enzymes increases because most proteases are characterized by promiscuous activity [18][19][20][21][22][23][24][25][26] .…”

Section: Introductionmentioning

confidence: 99%

Embracing enzyme promiscuity with activity-based compressed biosensing

Holt

Lim

et al. 2022

Preprint

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Genome-scale activity-based profiling of proteases requires identifying substrates that are specific to each individual protease. However, this process becomes increasingly difficult as the number of target proteases increases because most substrates are promiscuously cleaved by multiple proteases. We introduce a method - Substrate Libraries for Compressed sensing of Enzymes (SLICE) - for selecting complementary sets of promiscuous substrates to compile libraries that classify complex protease samples (1) without requiring deconvolution of the compressed signals and (2) without the use of highly specific substrates. SLICE ranks substrate libraries according to two features: substrate orthogonality and protease coverage. To quantify these features, we design a compression score that was predictive of classification accuracy across 140 in silico libraries (Pearson r = 0.71) and 55 in vitro libraries (Pearson r = 0.55) of protease substrates. We demonstrate that a library comprising only two protease substrates selected with SLICE can accurately classify twenty complex mixtures of 11 enzymes with perfect accuracy. We envision that SLICE will enable the selection of peptide libraries that capture information from hundreds of enzymes while using fewer substrates for applications such as the design of activity-based sensors for imaging and diagnostics.

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Fc microparticles can modulate the physical extent and magnitude of complement activity

Cited by 15 publications

References 66 publications

Optimizing Flux Capacity of Dead-end Filtration Membranes by Controlling Flow with Pulse Width Modulated Periodic Backflush

Optimizing Flux Capacity of Dead-end Filtration Membranes by Controlling Flow with Pulse Width Modulated Periodic Backflush

Pathogenesis of Drug Induced Non-Allergic Angioedema: A Review of Unusual Etiologies

Embracing enzyme promiscuity with activity-based compressed biosensing

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