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Erythrocyte fouling on micro-engineered membranes

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Abstract

Crossflow microfiltration of plasma from blood through microsieves in a microchannel is potentially useful in many biomedical applications, including clinically as a wearable water removal device under development by the authors. We report experiments that correlate filtration rates, transmembrane pressures (TMP) and shear rates during filtration through a microscopically high channel bounded by a low intrinsic resistance photolithographically-produced porous semiconductor membrane. These experiments allowed observation of erythrocyte behavior at the filtering surface and showed how their unique deformability properties dominated filtration resistance. At low filtration rates (corresponding to low TMP), they rolled along the filter surface, but at higher filtration rates (corresponding to higher TMP), they anchored themselves to the filter membrane, forming a self-assembled, incomplete monolayer. The incompleteness of the layer was an essential feature of the monolayer’s ability to support sustainable filtration. Maximum steady-state filtration flux was a function of wall shear rate, as predicted by conventional crossflow filtration theory, but, contrary to theories based on convective diffusion, showed weak dependence of filtration on erythrocyte concentration. Post-filtration scanning electron micrographs revealed significant capture and deformation of erythrocytes in all filter pores in the range 0.25 to 2 μm diameter. We report filtration rates through these filters and describe a largely unrecognized mechanism that allows stable filtration in the presence of substantial cell layers.

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Acknowledgements

Support for this work was provided in part by Grant 1R21HL088162 from the National Institute of Health, and Vizio Medical Devices, LLC. The authors also thank Columbia Medical Center Blood Bank and blood donors. We acknowledge gratefully the assistance of Dr. Robert von Gutfeld and to our whole medical team, especially Dr.Stanley Cortell and most especially the late Dr. James Jones.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA

    Levy I. Amar & Edward F. Leonard

  2. Department of Chemical Engineering, Columbia University, New York, NY, 10027, USA

    Daniela Guisado, Monica Faria, Michael I. Hill & Edward F. Leonard

  3. Department of Nephrology, Mount Sinai St. Luke’s Roosevelt Hospital, New York, NY, 10025, USA

    James P. Jones

  4. MicroFluidics and NanoTechnology/ORC, Wageningen University Stippeneng, Wageningen, 6708, WE, The Netherlands

    Cees J. M. van Rijn

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  1. Levy I. Amar
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  2. Daniela Guisado
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  3. Monica Faria
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  4. James P. Jones
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  5. Cees J. M. van Rijn
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Correspondence to Levy I. Amar.

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James P. Jones died before publication of this work was completed.

Topical area: Microfluidics, Separations: Materials, Devices, and Processes, Artificial Organs.

Appendix

Appendix

1.1 Nomenclature

B Half height of the channel (m)

J Permeate flux (m/s)

L Channel Length (m)

W Channel width (m)

ΔP Pressure drop across the channel (torr)

QF Volumetric flowrate of the permeate (i.e. Filtration rate) (cm3/min)

Qm Volumetric flowrate in main channel (cm3/min)

TMP Transmembrane pressure (torr)

a Particle radius (m)

dp Particle diameter

Am Membrane area (m2)

n0 number of pores per membrane

n number of open pores per membrane

FL Lift force (N)

FVDW Van der Waals force (N)

h Distance between the particle center and the membrane surface (cm)

Jf Filtrate flux (cm3/cm2-min)

KL Dimensionless constant in lift force

P Local hydrostatic pressure (torr)

P1 Outlet pressure (torr)

P2 Inlet pressure (torr)

P3 Filtrate pressure (torr)

mp Mass of particles in the cake (kg)

RM Resistance of membrane

RL Resistance of erythrocyte monolayer

RC Resistance of cake layer

1.2 Greek symbols

α Specific resistance of cake deposit

ε Fractional voidage of cake deposit

ρ fluid density (kg/m3)

γw Nominal wall shear rate (1/s)

τw Wall shear stress

ρp Particle density

η Viscosity of the media

μw Viscosity of pure water

1.3 Supporting data

Table 1 Intrinsic resistance (RM) of each membrane
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Fig. 9
figure 9

Maximum filtration rate is linearly dependent on shear rate (2000–8000 s−1), however, independent of solute concentration (hematocrit) at each shear rate

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Table 2 Calculated fluxes (J = Qf/Am ) for each pore geometry. Qf represents maximum filtration rate at its corresponding shear rate, and Am corresponds to the sieving area of 2.2 cm2
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Fig. 10
figure 10

Transmembrane pressure profile: Initial rising slope represents the time to reach steady state (section A). Plateau represents stable filtration under subcritical TMP (section B). Steep rising represents unstable filtration with cellular accumulation and jamming of the filtering membrane when filtrate rate was increased above critical TMP (section C). TMP drops back to 0 Torr when filtrate pump is stopped (at 560 s)

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Amar, L.I., Guisado, D., Faria, M. et al. Erythrocyte fouling on micro-engineered membranes. Biomed Microdevices 20, 55 (2018). https://doi.org/10.1007/s10544-018-0297-1

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