BIOM9311 Mass Transfer in Medicine

Week 1

J D

membrane

dc
dx

fluid 1

fluid 2

C1

C
1

C
2
x

C4

x1

x2

x3

x4

What is life?
Life is natures way of keeping meat fresh.
(Dr. Who?, 23/7/05)
Life is a set of ongoing controlled chemical reactions
occurring in prescribed locations.
Reactions need reactants
Delivery of reactants to the reaction site is mass
transfer (in part)

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Mass transfer applications

Blood processing
Haemodialysis
Oxygenator
Peritoneal dialysis
Haemofiltration
Plasmapheresis

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Drug delivery
Implants
Skin patches

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WithIn the body

Lungs
Kidneys
Capillaries
Tissue engineering
Biosensors

Background we need
We are dealing with solutes in different phases
Liquids (water, blood, lipid bilayer membrane)
Gases (air)
Membranes
We have to know
how species move within phases
what governs the distribution of species between
phases

We need a review of physical chemistry!

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Background we need (II)

We are interested in mass transfer devices or
physiological systems, often with fluid(s) flowing in
channel(s), always with a diffusion barrier
Haemodialyzer, oxygenator
Blood capillary in tissue, lung, skin

We have to know
The properties of the barrier
The effect of flow rates on the overall rate of transfer
The effect of flow channel dimensions

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Todays topics

Physical chemistry review

Material balances
Diffusion at a point
The diffusion coefficient
Diffusion across a finite distance
Diffusion across a membrane
Diffusion across a series of diffusion
resistances

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Physical Chemistry Review

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Ideal gas
T0 =
P0 =

V0 =
R =
=
=
=

PV
273.16K (0C)
1 atm = 760 mmHg
= 101.3 kPa
= 1.013 106 dyne/cm2
22.4 L for 1 gram-mole of gas
Universal Gas Constant
0.0821 atm L/K mol
8.31 44 Pa m3/K mol
1.99 cal/K mol
P0V0/T0 *** (I use this often)

nRT
Advice: Implement this
in Excel (say). Store
conversion factors for
P and values of R.

Real gases at atmospheric pressure are approximately

ideal.

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Gas mixtures - partial pressure

ni RT
ni
Pi
RT
V
V
P

P
i

RT
RT
ni
nT
V
V

n
Pi i P xi P
nT

ni
xi
nT

Mole fraction

The partial pressure of a gas is a measure of its concentration

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Thermodynamics - a brief encounter

Gibbs free energy - f (T,P,composition)
G
G
G
dG
dT
dP
T P,all ni
P T ,all ni
i ni
dG SdT VdP

dni
P,T ,all n j

dn
i

V
S
i

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volume
entropy
chemical potential of species i
Gibbs free energy per mole
the driving force for mass transfer by diffusion
(among other processes)

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Phase equilibrium
Phase: 4. Chem. A physically distinct and homogeneous form of matter characterized by
its state (as gas, liquid, or solid) and composition and separated by a bounding
surface from other forms. (OED)

Given a closed system at equilibrium

G is minimum
dG = 0
Two phases , in equilibrium:

T T
P P

The chemical potential of a

species is the same in both
phases at equilibrium
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i i

11

Ideal solutions
A binary solution of A and B and its equilibrium vapour phase:

Asoln Avapour

PA

Bsoln Bvapour
But

XA

PB

Vapour

XB

Solution

Avapour Ao RT ln PA

Therefore

Asoln Ao RT ln PA
Or better:

o
soln

A
A RT ln

PA
PAo

The chemical potential of A

molecules in solution is less
than the chemical potential of
pure A

Ideal solution (rare):

o
soln

A
A RT ln x A

PA x A PAo
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Osmotic pressure
When you dissolve a solute in a solvent,
you lower the chemical potential of the
solvent.
If the solution is separated from pure
solvent by a semi-permeable membrane
(permeable to the solvent but not the
solute), solvent will flow from the pure
side to the solution side.
If sufficient pressure is applied to the
solution, the osmotic flow can be
overcome.
This pressure is the osmotic pressure. It
is the hydrostatic pressure required to
overcome the osmotic flow.
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A+B

A A

13

Osmotic pressure
At equilibrium we have

A A
but

A Ao RT ln

whereas

P = P+

PA

A+B

PAo

A oA

So we increase P until there is

no flow

P P

A A

is the osmotic pressure. It is the hydrostatic pressure required to

overcome the osmotic flow. This is the definition of osmotic
pressure.
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Osmotic pressure
Vant Hoffs Law (ideal solutions)
Van't Hoff

cRT

Where c is the molar concentration of B. If more than one

solute (e.g., an electrolyte that dissociates into 2 or more
ions)

ci RT
i

Most solution are not ideal. We refer to the osmolarity, the

concentration of the ideal solution that has the same

osmolarity
At 37C

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RT

(mmHg ) 19.3 c(mOsmol / L)

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Concentrations
A concentration is a ratio:

amount of X
amount of Y

We will encounter a wide variety ways of expressing a

concentration. For example
Molar:

moles of i
ci
(mol/L)
litre of solution

Blood gases:

ml O 2 ( STP)
cO2
ml blood
Mole fraction:

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Why specify STP?

moles A
xA
total moles

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Vapor/liquid equilibrium: Henry's law

Empirically, there is a linear relationship between the partial
pressure of a gas, Pi, and its equilibrium concentration in
solution, ci.

ci kPi

Some solubility coefficients in water at 37C (ex Guyton)

(ml (STP)/ml solution/atm)

gas
Oxygen
Carbon dioxide
Carbon monoxide
Nitrogen
Helium

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k
0.024
0.57
0.018
0.012
0.008

High solubility of
CO2 in water
has implications

17

Liquid/liquid equilibrium:
Partition coefficients

II

For species i, at equilibrium

iII iI
Define a partition coefficient i
such that

ciII i ciI
solute
glycerol
ethanol
N-propanol

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phase I
water
"
"

Phase II
olive oil
"
"

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0.000068
0.022
0.1

Does this
series make
sense?
Write the
formulas of
these three
alcohols.

18

lung
right
heart

left
heart

5%

The
circulation
(for reference)

heart

15
%
35%

brain
liver
gut

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15%

muscle

20%

kidneys

10%

skin,bone

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The mass (material balance)

The solutions of many mass transfer problems begin with a
mass (or material) balance on one or more chemical species.
A material balance is expressed in terms of an extensive
property about which conservation statements can be made.
Intensive properties
Concentration in moles/L
Temperature
Density
Extensive properties
Mass in kg or moles of a chemical compound
Number of moles of an element
The volume in L of a fluid

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The mass (material balance)

input

accumulation

output

rate of rate of rate of rate of rate of

accumulation
input
output
synthesis

destruction

Define a species (X) and a control volume.

Identify every process that adds that species to or
removes it from the control volume.
Derive an algebraic equation (if steady state).

Derive a differential equation (if not steady state).

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Example

Liquid flowing into and out of a device, steady state

Rule: Volume flow rate in = Volume flow rate out

210 ml/min

? ml/min

Under what
Assumptions?

220 ml/min

175 ml/min

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Example
Solutions flowing into and out of a device, steady state

Rule: Volume flow rate in = Volume flow rate out

Rule: Solute X mass flow rate in = Solute X mass flow rate out

210 ml/min

c = 0.4M

Assumptions?
185 ml/min
c= ? M

220 ml/min
c = 0.9M

175 ml/min
c = 0.5M
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Example

What is rate of solute transfer from white fluid to red

fluid?

210 ml/min
c = 0.4 M

N ?

220 ml/min
c = 0.9 M

185 ml/min
c = 1.09 M

175 ml/min
c = 0.5 M
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Example

300 ml/min
c= 0 M

200 ml/min

200 ml/min
c= 2 M

Minimum possible c = ? M
Maximum possible c = ? M
300 ml/min
Minimum possible c = ? M
Maximum possible c = ? M

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Example
Minimum possible c = ?

c= 2 M
200 ml/min

200 ml/min

300 ml/min
c= 0

300 ml/min

Maximum possible c = ?

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Example
Minimum
possible c = ?

c= 2 M
200 ml/min

200 ml/min

300 ml/min
Maximum
possible c = ?

300 ml/min
c= 0

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Diffusion - microscopic theory

(ex Berg: Random walks in biology)
The mean kinetic energy (k.e.) of a molecule due to thermal
motion is 3/2 kT split 3 ways among the x, y, z directions. (k is
Boltzmanns constant = R/Navog.)
For the x-direction

k.e.

1m
2

vx2

1 kT
2

The r.m.s x velocity is therefore

vx2

kT / m

How fast is that?

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example: Lysozyme (MW = 14,000) at 310 K

12
vx2

kT

RT

8.3110 erg K
7

-1

mol-1 310K

14000 g mol-1

1356cm s 1

Of course our lysozyme molecule wont travel very far in a

straight line. It will bump into a water molecule and be sent
off in a random direction.
Hence the random walk

Large molecules move more slowly

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The 1D random walk

Rules
1. A particle starts at x = 0 and moves L or R with a velocity vx
once every seconds. The distance travelled each step is vx
= .
2. Moving left and right are equally likely and each step is
independent of all previous steps: P(L) = P(R) = 1/2.
3. Each particle is independent of all other particles (dilute).
diffdemo1a.m

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From rule one, the position of particle i after step n is

xi (n) xi (n 1)
Averaging over all particles
1
x ( n)
N
1

N
1

x ( n)
i 1

x (n 1)
i

i 1
N

x (n 1)
i 1

We are not making

any progress!

x(n) x(n 1)

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The +s and s will

tend to cancel out,
so if N is large

No net movement

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The particles do become spread out, however, some to the

left and some to the right.
2

A measure of this is the r.m.s displacement x (n)

Again, starting from Rule one

xi (n) xi (n 1)
Squaring,

xi2 (n) xi2 (n 1) 2xi (n 1) 2

taking the average, again using Rule two,

x 2 (n) x 2 (n 1) 2
or

x 2 (n) n 2

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If we define
we get
or

2
D
2
x 2 (t ) 2 Dt
2

x (t )

2 Dt

The spread is proportional to the square root of t.

The characteristic time for a diffusive process is
(forget about the 2)

tdiff

L2 D

Is diffusion fast or slow?

Diffdemo1a.m, Diffdemo2.m, Diffdemo3.m

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Diffusion: Macroscopic theory

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Flux
The flux of X is the flow of X, per unit
area, with respect to a coordinate system.
If the mean relative velocity of X is v and
its concentration is ci, the flux is

J cv

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-2 -1

ML T

kg m-2 s-1

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Convection
The flow of matter (or heat) due to the
bulk motion of a fluid.

vci

If the fluid is moving with velocity v, the

convection flux of species i is

J i ci v
If a fluid is flowing in a conduit with crosssection area A, the total flow of species i is

Ni Ji A ci v A Qci

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Qci

36

Diffusion

before

after

There has been net movement

red molecules to the right
yellow molecules to the left
After mixing, no more net movement
Random motion + concentration gradient diffusion

These 2 wiki pages are of interest primarily for the graphics

http://en.wikipedia.org/wiki/Molecular_diffusion
http://en.wikipedia.org/wiki/Diffusion

diffdemo2a.m
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Ficks (first) Law

Postulate: there is a linear relationship between the diffusion
flux of species i and the concentration gradient.
In one dimension (x)

dci
J xi Di
dx

Units: [J] = ML-2T-1

[D] = L2T-1
Warning: The length units on J come from c, x, and D. Serious
potential for error!

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Diffusion coefficient D
Depends on

- the diffusing species (size of the molecule)

- the medium in which it diffusing
Much faster in gases than in liquids
An approximate theory follows

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Nernst-Einstein equation
kTvA kT
DAB

FA
fA
k

Boltzmanns constant =R/Navog

FA

friction force on an A molecule moving with velocity vA

fA

is a friction factor = FA/vA

So
D = thermal energy / friction factor

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Stokes law
The friction factor for a spherical molecule of radius rA in a
medium with viscosity B is
What is viscosity?
(resistance to flow)

fA 6 BrA
Stokes-Einstein

DAB

kT
6 BrA

For a spherical molecule, molecular weight MA, density A , the

radius is

3M A

rA
4 A N Avog

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1
3

41

Example
For aqueous solutions at 37C, assume solute molecular density ~1
7

-1

R = 8.31410 erg mol K

T = 310 K
N Avog = 6.02 x 1023 mol-1

-1

A = 1 g cm-3
B = 0.0069 dyne s cm-2

-1

8.314 J mol K

-1

1000 kg m-3
0.00069 Pa s

1 Da = 1 g mol-1
For M = 1000 Da, we find
r = 7.35x10-10 m
D = 4.48x10-10 m2 s-1

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Advice:
Implement this in Excel (say).
Make a table of MW vs. D

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Some diffusion coefficients at 37C (Keller)

Substance
Oxygen
Carbon dioxide
Urea
Albumin
Oxygen

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Medium
Water
"
"
"
air

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D (cm2/sec)
3.1 10-5
2.6 10-5
1.9 10-5
1 10-6
0.15

43

A series from Colton

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The one-dimension diffusion equation

(Ficks 2nd law)
Assume concentration depends on x only and that the
velocity is zero. (Diffusion only.)
diffusion
in at x

diffusion
out at x+dx
x

x+dx

Material balance: accumulation = input - output

c( x, t )
dxdydz J x ( x, t )dydz J x ( x dx, t )dydz
t

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Dividing by dxdydz we get

J ( x, t )
c( x, t ) J x ( x, t ) J x ( x dx, t )

x
t
dx
x
or simply

J
c
x
t
x

Substitute Ficks first law

Jx D
to give

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c
x

c
2c
D 2
t
x

Week 1

Ficks 2nd law in 1D

46

Steady diffusion through a stationary film

Given:
<v> = 0 no flow
c = c(x) one dimension, steady state
Boundary conditions
c(x1) = c1
c(x2) = c2
Apply Ficks 2nd law

J D
C
1

C
2
x

c
J

0 (steady state)
t
x
Flux is independent of position if SS. Therefore the
concentration profile is linear.

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dc
dx

47

Substitute Ficks 1st law. We have several ways to express the

flux:
dc
J constant D
dx
x1 x2
c c
D
D 1 2
c1 c2 k c1 c2
x1 x2

c c
c c
1 2 1 2
R D
D
R

The quantity D/ has the units L T-1.

and is known as the mass transfer coefficient, k.
The inverse, /D is the mass transfer resistance.
Sometimes it is easier to work in terms of k, other times it is more
convenient to work in terms of resistances.

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Diffusion through a membrane

Assume that
the membrane is homogeneous
the diffusion coefficient of the solute
in the membrane is Dm
<v> = 0
Steady State
Again, flux J is independent of position
and is given by

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Dm

C1
C1m

C2
C2m

c1m is the concentration

within the membrane at
surface 1.

c1m c2m

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To express the flux in terms of the concentrations in the fluid

phases, we use partition coefficients

c1m mc1
We now write

Dm m

c1 c2 Pm c1 c2

Pm

Dm m

The permeability of a membrane to a solute is determined by

three factors:
1.The membrane thickness .
2.The chemical interaction between the solute and the
membrane m (in effect, solubility)
3.The frictional interaction of solute and membrane,
through Dm.
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Resistances in series
Usually we must consider 2 or more
resistances in series, as in this 2chamber diffusion apparatus. We want to
relate the flux to the difference between
the measured concentrations in samples
taken from the chambers.

membrane
fluid 1

A conceptual model is at the right.

Well mixed x < x1 and x > x4

Unstirred fluid x1< x < x2,

fluid 2

C1

x 3< x < x 4

Membrane x2< x < x3

C4
x1

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x2

x3
51

x4

Assume
<v> = 0
1 = 2 = 3 = 1
SS

For any x1 < x < x4 the flux is independent of x. (Why?)

dc
J constant Dn
dx

n 1, 2,3

For the 3 phases we have

c3 c2
c4 c3
c2 c1
J D1
D2
D3
x2 x1
x3 x2
x4 x3

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Solving for c1 - c2 etc.,

c1 c2

J ( x2 x1 ) J
JR1
D1
P1

J ( x3 x2 ) J
c2 c3

JR2
D2
P2
c3 c4

J ( x4 x3 ) J

JR3
D3
P3

The sum

c1 c4

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J J
J
J R1 R2 R3
P1 P2 P3

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Defining the overall permeability

J
Po
c1 c4
we find

1
1 1
1

Po P1 P2 P3

or in terms of resistances

Ro R1 R2 R3
Easier to work with resistances when we have multiple layers!

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References
Berg HC: Random walks in Biology. Princeton, Princeton
University Press (1993).
Cussler EL: Diffusion: Mass transfer in fluid systems.
Cambridge, Cambridge University Press (1984).
Fournier RL: Basic transport phenomena in biomedical
engineering. Taylor and Francis (2012)
Trusky GA, Yuan Fan, Katz DF: Transport Phenomena in
Biological Systems, Pearson Prentice Hall (2004). GSBME
library.
Keller KH: Fluid mechanics and mass transfer in artificial
organs. (1973).

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