- Email: [email protected]
Separation of red blood cells by magnetic means
LETTER TO THE EDITOR
Journal of Magnetism and Magnetic Materials 220 (2000) L103}L105
Letter to the Editor
Separation of red blood cells by magnetic means Jan Svoboda DebTech, De Beers Diamond Research Laboratory, P.O. Box 82851, Southdale 2135, Johannesburg, South Africa Received 18 May 2000
Abstract A recent article by Haik et al. is critically reviewed. It is shown that the techniques of separation of red blood cells proposed by the above authors are unlikely to work and that high-gradient magnetic separation is probably the only viable method of separation of erythrocytes. 2000 Elsevier Science B.V. All rights reserved.
The separation of erythrocytes (red blood cells) from the remainder of the blood components using magnetic means has received considerable attention during the last 20 years. An innovative approach by a group of researchers from the Southampton University and other organisations [1}5] resulted in the development of a novel method of erythrocyte separation by high-gradient magnetic separation (HGMS). This technique is based on the fact that the paramagnetic properties of the reduced haemoglobin of erythrocytes allow capture of these cells under suitable conditions. By diluting fresh, anticoagulated blood in an isotonic reducing agent, the iron of haemoglobin is reduced to the paramagnetic Fe> form. In the presence of a non-homogeneous magnetic "eld a force is exerted on these particles, which allows the red blood cells to be separated from the whole blood. A typical HGMS device consists of a steel-wool matrix, magnetised by an external magnetic "eld. Very high "eld gradients thus generated allow the erythrocytes to be captured by the steel wires and separated from the rest of the blood.
E-mail address: [email protected] (J. Svoboda).
Results of these studies were published extensively [1}5]. In a recent article by Haik et al. [6], the problem of the separation of red blood cells was revisited. The paper in question did not re#ect the previous successful approach to the problem and ignored the extensive research results in this "eld. It was also assumed that the blood would be a!ected by an essentially homogeneous magnetic "eld generated by a solenoid magnet. Furthermore, it was expected that the direction of the "eld (parallel or antiparallel), with respect to the direction of #ow, would a!ect the #ow of the blood. However, it is well known that a force exerted on a magnetisable particle (e.g. erythrocyte) is not a function of the direction of the magnetic "eld vector, but is determined by the modulus of the magnetic "eld strength and the direction of the magnetic "eld gradient. The direction and the sense of the magnetic "eld vector are meaningless in this exercise, as transpires from the expression of the magnetic force [7] (incorrectly quoted in Ref. [6]): i < F " T (B ) )B,
k
0304-8853/00/$ - see front matter 2000 Elsevier Science B.V. All rights reserved. PII: S 0 3 0 4 - 8 8 5 3 ( 0 0 ) 0 0 4 7 9 - 0
(1)
LETTER TO THE EDITOR
L104
J. Svoboda / Journal of Magnetism and Magnetic Materials 220 (2000) L103}L105
where i and V are the volume magnetic susceptiT bility and volume of a particle, respectively, k is the magnetic permeability of vacuum and B is the magnetic "eld induction. In order to assess the potential for red blood cells to be a!ected by the magnetic "eld and thus to be separated from the whole blood, it is necessary to evaluate the magnetic force given by Eq. (1) and to compare it with the competing forces acting on erythrocytes. Hydrodynamic drag and the force of gravity are the most important competing forces acting on particles in HGMS. The hydrodynamic drag is given by the following equation: F "6pgb*, (2) where g is the viscosity of the #uid, b is the radius of the particle and v is the relative velocity of a particle. The force of gravity is F "
The magnetic capture force will be dominant if F 'F ; thus, 2.4;10\ B'2.5;10\ which
yields B'10 T m\. This is a very high "eld gradient indeed and it is clear that the approach employed in [6] fails to meet this requirement by at
least four-orders of magnitude. It is obvious that the study [6] does not even remotely meet the basic conditions for magnetic manipulation of very feebly magnetic particles such as erythrocytes. It also fails to recognise the essential role of the gradient of the magnetic "eld and its relationship with the competing forces, in particular the hydrodynamic drag acting on the particles to be separated. On the other hand, it is fairly simple to manipulate the red blood cells by magnetic means using a ferromagnetic matrix, as described in Refs. [1}5]. The "eld gradient can be approximated [7] as
B"M /a where M is the saturation magnetisa tion of the matrix material and a is the radius of the matrix element. Assuming that M "2 T we obtain
B'10 T m\ for a'200 lm. Filaments of the ferromagnetic matrix with a radius greater than 200 lm will thus generate the "eld gradient su$cient to remove red blood cells from the whole blood. We have thus shown that one of the two approaches to the separation of red blood cells from the whole blood as proposed in Ref. [6] is unlikely to work, from "rst principles. On the other hand it might be possible, by combining erythrocytes with strongly magnetic bodies, to compensate for the very low "eld gradient used in Ref. [6]. However, an increase in magnetic susceptibility by at least "ve-orders of magnitude is required, as follows from the above analysis. If we assume the saturation magnetisation of the magnetic carriers to be used to attach erythrocytes to be 0.1 T (assuming 20% concentration of magnetite), then the corresponding magnetic susceptibility at the operating magnetic "eld will be approximately 0.05 (SI). This is almost an order of magnitude less that the required susceptibility of 0.39 (3.9;10\;10). On the other hand, high-gradient magnetic separation of erythrocytes, as demonstrated in several published reports, was shown to be viable based on the balance of the forces. References [1] D. Melville, F. Paul, S. Roath, High gradient magnetic separation of red cells from whole blood, IEEE Trans. Magn. 11 (1975) 1701.
LETTER TO THE EDITOR
J. Svoboda / Journal of Magnetism and Magnetic Materials 220 (2000) L103}L105 [2] S. Roath, F. Paul, D. Melville, High gradient magnetic separation of red blood cells: current status, in: P. Somasundaran (Ed.), Proceedings of the International Symposium On Fine Particles Processing, Las Vegas, NV, USA, AIME New York, 1980, p. 1287. [3] M.D. Graham, E$ciency comparison of two preparative mechanisms for magnetic separation of erythrocytes from whole blood, J. Appl. Phys. 52 (1981) 2578. [4] D. Mellvile, F. Paul, S. Roath, Fractionation of blood components using high gradient magnetic separation, IEEE Trans. Magn. 18 (1982) 1680.
L105
[5] A.J. Richards, O.S. Roath, R.J.S. Smith, J.H.P. Watson, The mechanisms of high gradient magnetic separation of human blood and bone marrow, IEEE Trans. Magn. 32 (1996) 459. [6] Y. Haik, V. Pai, Ching-Jen Chen, Development of magnetic device for cell separation, J. Magn. Magn. Mater. 194 (1999) 254. [7] J. Svoboda, Magnetic Methods for the Treatment of Minerals, Elsevier, Amsterdam, 1987.
Journal of Magnetism and Magnetic Materials 220 (2000) L103}L105
Letter to the Editor
Separation of red blood cells by magnetic means Jan Svoboda DebTech, De Beers Diamond Research Laboratory, P.O. Box 82851, Southdale 2135, Johannesburg, South Africa Received 18 May 2000
Abstract A recent article by Haik et al. is critically reviewed. It is shown that the techniques of separation of red blood cells proposed by the above authors are unlikely to work and that high-gradient magnetic separation is probably the only viable method of separation of erythrocytes. 2000 Elsevier Science B.V. All rights reserved.
The separation of erythrocytes (red blood cells) from the remainder of the blood components using magnetic means has received considerable attention during the last 20 years. An innovative approach by a group of researchers from the Southampton University and other organisations [1}5] resulted in the development of a novel method of erythrocyte separation by high-gradient magnetic separation (HGMS). This technique is based on the fact that the paramagnetic properties of the reduced haemoglobin of erythrocytes allow capture of these cells under suitable conditions. By diluting fresh, anticoagulated blood in an isotonic reducing agent, the iron of haemoglobin is reduced to the paramagnetic Fe> form. In the presence of a non-homogeneous magnetic "eld a force is exerted on these particles, which allows the red blood cells to be separated from the whole blood. A typical HGMS device consists of a steel-wool matrix, magnetised by an external magnetic "eld. Very high "eld gradients thus generated allow the erythrocytes to be captured by the steel wires and separated from the rest of the blood.
E-mail address: [email protected] (J. Svoboda).
Results of these studies were published extensively [1}5]. In a recent article by Haik et al. [6], the problem of the separation of red blood cells was revisited. The paper in question did not re#ect the previous successful approach to the problem and ignored the extensive research results in this "eld. It was also assumed that the blood would be a!ected by an essentially homogeneous magnetic "eld generated by a solenoid magnet. Furthermore, it was expected that the direction of the "eld (parallel or antiparallel), with respect to the direction of #ow, would a!ect the #ow of the blood. However, it is well known that a force exerted on a magnetisable particle (e.g. erythrocyte) is not a function of the direction of the magnetic "eld vector, but is determined by the modulus of the magnetic "eld strength and the direction of the magnetic "eld gradient. The direction and the sense of the magnetic "eld vector are meaningless in this exercise, as transpires from the expression of the magnetic force [7] (incorrectly quoted in Ref. [6]): i < F " T (B ) )B,
k
0304-8853/00/$ - see front matter 2000 Elsevier Science B.V. All rights reserved. PII: S 0 3 0 4 - 8 8 5 3 ( 0 0 ) 0 0 4 7 9 - 0
(1)
LETTER TO THE EDITOR
L104
J. Svoboda / Journal of Magnetism and Magnetic Materials 220 (2000) L103}L105
where i and V are the volume magnetic susceptiT bility and volume of a particle, respectively, k is the magnetic permeability of vacuum and B is the magnetic "eld induction. In order to assess the potential for red blood cells to be a!ected by the magnetic "eld and thus to be separated from the whole blood, it is necessary to evaluate the magnetic force given by Eq. (1) and to compare it with the competing forces acting on erythrocytes. Hydrodynamic drag and the force of gravity are the most important competing forces acting on particles in HGMS. The hydrodynamic drag is given by the following equation: F "6pgb*, (2) where g is the viscosity of the #uid, b is the radius of the particle and v is the relative velocity of a particle. The force of gravity is F "
The magnetic capture force will be dominant if F 'F ; thus, 2.4;10\ B'2.5;10\ which
yields B'10 T m\. This is a very high "eld gradient indeed and it is clear that the approach employed in [6] fails to meet this requirement by at
least four-orders of magnitude. It is obvious that the study [6] does not even remotely meet the basic conditions for magnetic manipulation of very feebly magnetic particles such as erythrocytes. It also fails to recognise the essential role of the gradient of the magnetic "eld and its relationship with the competing forces, in particular the hydrodynamic drag acting on the particles to be separated. On the other hand, it is fairly simple to manipulate the red blood cells by magnetic means using a ferromagnetic matrix, as described in Refs. [1}5]. The "eld gradient can be approximated [7] as
B"M /a where M is the saturation magnetisa tion of the matrix material and a is the radius of the matrix element. Assuming that M "2 T we obtain
B'10 T m\ for a'200 lm. Filaments of the ferromagnetic matrix with a radius greater than 200 lm will thus generate the "eld gradient su$cient to remove red blood cells from the whole blood. We have thus shown that one of the two approaches to the separation of red blood cells from the whole blood as proposed in Ref. [6] is unlikely to work, from "rst principles. On the other hand it might be possible, by combining erythrocytes with strongly magnetic bodies, to compensate for the very low "eld gradient used in Ref. [6]. However, an increase in magnetic susceptibility by at least "ve-orders of magnitude is required, as follows from the above analysis. If we assume the saturation magnetisation of the magnetic carriers to be used to attach erythrocytes to be 0.1 T (assuming 20% concentration of magnetite), then the corresponding magnetic susceptibility at the operating magnetic "eld will be approximately 0.05 (SI). This is almost an order of magnitude less that the required susceptibility of 0.39 (3.9;10\;10). On the other hand, high-gradient magnetic separation of erythrocytes, as demonstrated in several published reports, was shown to be viable based on the balance of the forces. References [1] D. Melville, F. Paul, S. Roath, High gradient magnetic separation of red cells from whole blood, IEEE Trans. Magn. 11 (1975) 1701.
LETTER TO THE EDITOR
J. Svoboda / Journal of Magnetism and Magnetic Materials 220 (2000) L103}L105 [2] S. Roath, F. Paul, D. Melville, High gradient magnetic separation of red blood cells: current status, in: P. Somasundaran (Ed.), Proceedings of the International Symposium On Fine Particles Processing, Las Vegas, NV, USA, AIME New York, 1980, p. 1287. [3] M.D. Graham, E$ciency comparison of two preparative mechanisms for magnetic separation of erythrocytes from whole blood, J. Appl. Phys. 52 (1981) 2578. [4] D. Mellvile, F. Paul, S. Roath, Fractionation of blood components using high gradient magnetic separation, IEEE Trans. Magn. 18 (1982) 1680.
L105
[5] A.J. Richards, O.S. Roath, R.J.S. Smith, J.H.P. Watson, The mechanisms of high gradient magnetic separation of human blood and bone marrow, IEEE Trans. Magn. 32 (1996) 459. [6] Y. Haik, V. Pai, Ching-Jen Chen, Development of magnetic device for cell separation, J. Magn. Magn. Mater. 194 (1999) 254. [7] J. Svoboda, Magnetic Methods for the Treatment of Minerals, Elsevier, Amsterdam, 1987.