Membrane based bioseparation Recovery & Isolation

Definition A membrane is a thin semi-permeable barrier which can be used for the following types of separation 1. Particle-liquid separation 2. Particle-solute separation 3. Solute-solvent separation 4. Solute-solute separation

Factors utilized in membrane-based separation, 1. Solute size 2. Electrostatic charge 3. Diffusivity 4. Solute shape

Purification

Mode of Membrane Separation Spiral Wound Hollow Fiber

Filtration Mode

microfiltration

Microfiltration Microfiltration membranes are microporous and retain particles by a purely sieving mechanism. Typical permeate flux values are higher than in ultrafiltration processes even though microfiltration is operated at much lower TMP. A microfiltration process can be operated either in a dead-end (normal flow) mode or cross-flow mode TMP = trans-membrane pressure

Applications of Microfiltration in downstream processing Cell harvesting from bioreactors 2. Virus removal for pharmaceutical products 3. Clarification of fruit juice and beverages 4. Water purification 5. Air filtration 6. Sterilization of products

Transport Equation δc = Cake layer For micron sized particles

Example Bacterial cells having 0.8 micron average diameter are being microfiltered in the cross-flow mode using a membrane having an area of 100 cm2. The steady state cake layer formed on the membrane has a thickness of 10 microns and a porosity of 0.35. If the viscosity of the filtrate obtained is 1.4 centipoise, predict the volumetric permeate flux at a transmembrane pressure of 50 kPa. When pure water (viscosity = 1 centipoise) was filtered through the same membrane at the same transmembrane pressure, the permeate flux obtained was 10-4 m/s.

solution

Batch Filtration (Incompressible Cake) V= total volume of filtrate ρo = mass of cake solids per volume of filtrate t=0, V=0 y = mx+c

Example2 A broth containing the yeast was filtered using microfilter and its time needed to collect the volume of filtrate is as below Filtration Time (sec) Volume of filtrate (ml) 2 20 10 56 25 90 50 175 The microfilter has a total area of 9 x 10-3 m2 and the filtrate has a viscosity of 1.15 cP. The pressure drop is 68,000 Pa and the feed contains 0.01 kg dry cake per liter Determine the specific cake and membrane resistance

ULTRAFILTRATION

Ultrafiltration UF membranes can retain macromolecular solutes. Solute retention is mainly determined by solute size. Other factors such as solute-solute and solute- membrane interactions can affect solute retention. Ultrafiltration is used for: Concentration of solutes Purification of solvents Fractionation of solutes Clarification

Ultrafiltration in downstream processing UF is widely used for processing: therapeutic drugs, enzymes, hormones, vaccines, blood products antibodies.

Ultrafiltration The major areas of application are listed below: Purification of proteins and nucleic acids Concentration of macromolecules Desalting, i.e. removal or salts and other low molecular weight compounds from solution of macromolecules Virus removal from therapeutic products

Ultrafiltration The ability of an ultrafiltration membrane to retain macromolecules is traditionally specified in terms of its molecular cut-off (MWCO). A MWCO value of 10 kDa means that the membrane can retain from a feed solution 90% of the molecules having molecular weight of 10 kDa. Ultrafiltration separates solutes in the molecular weight range of 5 kDa to 500 kDa. UF membranes have pores ranging from 1 to 20 nm in diameter.

Transport Equations The solvent flow is proportional to the applied force (solvent velocity) α (force on solvent) Lp is the solvent permeability Include the osmotic pressure For solute leak through the membrane σ is the reflection coefficient, 0 < σ <1

Governing laws – darcy law Darcy's law is a simple proportional relationship between the instantaneous discharge rate through a porous medium, the viscosity of the fluid and the pressure drop over a given distance. The total discharge, Q (units of volume per time, e.g., m3/s) is equal to the product of the permeability of the medium, k (m2), the cross-sectional area to flow, A (units of area, e.g., m2), and the pressure drop (Pa), all divided by the viscosity, μ (Pa.s) and the length the pressure drop is taking place over.

Model-Poiseuille flow The flow of a solvent through ultrafiltration membranes can be described in terms of a pore flow model which assumes ideal cylindrical pores aligned normal to the membrane surface:

Transmembrane Pressure The transmembrane pressure in cross-flow UF is given by:

concentration polarization the retained macromolecules accumulate near the membrane surface caused concentration polarization. At steady state, a stable concentration gradient exists near the membrane owing to back diffusion of solute from the membrane surface. offers extra hydraulic resistance to the flow of solvent development of osmotic pressure which acts against the applied transmembrane pressure

model As most ultrafiltration membranes can not be visualized as having parallel cylindrical pores, a parameter, the membrane hydraulic resistance is used for calculating permeate flux:

If the solute build-up is extensive, a gel layer may be formed on top of the membrane

Limiting flux At lower values of transmembrane pressure, the permeate flux increases linearly with increase in pressure However, as the pressure is further increased, there is deviation from the solvent profile, this being due to concentration polarization. At very high transmembrane pressures, the permeate flux usually plateaus off, clearly suggesting the formation of a gel layer.

Limiting Flux Beyond this point, increasing the transmembrane pressure has a negligible effect on the permeate flux This value of permeate flux being referred to as the limiting flux (Jlim).

Crossflow filtration The fluid in crossflow filtration flows parallel to the membrane surface, resulting in constant permeate flux at steady state

Model

Concentration polarization model At steady state, a material balance of solute molecules in a control volume within the concentration polarization layer yields the following differential equation:   Integrating this with boundary conditions (C = Cw at x = 0; C = Cb at x = b), we get k (= mass transfer coefficient) = D / b

Concentration polarization model For total solute rejection, i.e., when Cp = 0, the equation reduces to

Ultrafiltration-Example 1 A protein solution (concentration = 4.4 g/1) is being ultrafiltered using a spiral wound membrane module, which totally retains the protein. At a certain transmembrane pressure the permeate flux is 1.3 x 10-5 m/s. The diffusivity of the protein is 9.5 x 10-11 m2/s while the wall concentration at this operating condition is estimated to be 10 g/1. Predict the thickness of the boundary layer. If the permeate flux is increased to 2.6 x 10-5 m/s while maintaining the same hydrodynamic conditions within the membrane module, what is the new wall concentration?

Ultrafiltration-model-solute mass transfer coefficient The solute mass transfer coefficient (k) is a measure of the hydrodynamic conditions within a membrane module. The mass transfer coefficient can be estimated from correlations involving the: Sherwood number (Sh), Reynolds number (Re), and Schmidt number (Sc):

These correlations are based on heat and mass transfer analogy. In the case of fully developed laminar flow, the Graetz-Leveque correlation can be used: For turbulent flow (i.e. Re > 2000), the Dittus- Boelter correlation can be used:

Membrane performance - retention If a solute is not totally retained (or rejected), the amount of solute going through the membrane can be quantified in terms of the membrane intrinsic rejection coefficient (R,) or intrinsic sieving coefficient (S,): More practical parameters such as the apparent rejection coefficient (Ra) or the apparent sieving coefficient (Sa) are frequently preferred:

A correlation between the intrinsic sieving coefficient and the apparent sieving coefficient can be obtained as: If the intrinsic sieving coefficient could be considered a constant, above equation provides a way by which the mass transfer coefficient and the intrinsic sieving coefficient could be determined by plotting experimental data

Example The intrinsic and apparent rejection coefficients for a solute in an ultrafiltration process were found to be 0.95 and 0.63 respectively at a permeate flux value of 6 x 10-3 cm/s. What is the solute mass transfer coefficient?

Membrane Performance - flux The permeate flux in an ultrafiltration process determines its productivity The permeate flux depends on: properties of the membrane Properties of the feed solution. transmembrane pressure the solute mass transfer coefficient (which affects the concentration polarization). membrane fouling

Enhancing permeate flux By increasing the cross-flow rate By creating pulsatile or oscillatory flow on the feed side By back flushing the membrane By creating turbulence on the feed side using inserts and baffles By sparging gas bubbles into the feed

Membrane performance - retention The retention of a solute by a membrane primarily depends of on the solute diameter to pore diameter ratio. the solute shape, solute charge, solute compressibility, solute-membrane interactions (which depend on the solution conditions) operating conditions (such as cross-flow velocity and transmembrane pressure).

NANOFILTRATION

Nanofiltration Nanofiltration (NF) membranes allow salts and other small molecules to pass through but retain larger molecules such as peptides, hormones and sugars. The transmembrane pressure in NF ranges from 40 to 200 psig.

Governing laws - Fick’s 1st law Fick's first law relates the diffusive flux to the concentration field, by postulating that the flux goes from regions of high concentration to regions of low concentration, where J is the diffusion flux in dimensions of [(amount of substance) length−2 time−1] D is the diffusion coefficient or diffusivity in dimensions of [length2 time−1] (for ideal mixtures) Φ is the concentration in dimensions of [(amount of substance) length−3], x is the position [length],

Governing laws - Fick’s 2ND law Fick's second law predicts how diffusion causes the concentration field to change with time (derived from Fick's First law and the mass balance): Where Φ is the concentration in dimensions of [(amount of substance) length−3], t is time [s] D is the diffusion coefficient in dimensions of [length2 time−1], x is the position [length]

The extended Nernst-Planck equation proposed by Schlogl and Dresner forms the basis of the description of ion transport through the membranes. The equation can be expressed as

Reverse Osmosis Reverse osmosis (RO) membranes allow water to go through but retain all dissolved species present in the feed. In osmosis water travels from the lower solute concentration side to the higher solute concentration side of the membrane. In RO the reverse takes place due to the application of transmembrane pressure. The normal transmembrane pressure range in RO is from 200 to 300 psig.