DE3236310A1 - METHOD AND DEVICE FOR SEPARATING A LIQUID FILTRATE - Google Patents

Description

COBE Laboratories, Inc. "11,283

1201 Oak Street
Lakewood, Colorado 80215

USA "-.- ■■

Method and device

to deposit a

liquid filtrate

The invention relates to the separation of liquid filtrates which do not contain any particles exceeding a certain size, of liquid particle mixtures.

According to the invention is a microporous membrane filter device provided with a device, which the geometry of either the flow channel for the particle! mixture or of the filtrate channel changed during operation. This creates increased versatility in varying different Control parameters of the device as a function of prevailing or desired operating conditions, such as throughput in the inlet, particle concentration in the inlet or Filtration rate. These operating conditions can change over time or · from application to application change. For example, a desired throughput can be maintained when feeding the particle mixture to the device.

- 20-

and you can vary the shear and other control parameters just by adjusting the channel height, to optimize the flow, but to avoid clogging and rupture of the particle cell walls.

Preferred embodiments are characterized by the following features marked: The height of the flow channel provided for the particle mixture, which is opposite the membrane, is varied by compressing the membrane separator. the membrane separator is in a holder between a front plate and, a piston plate, which runs along a transverse to the front plate extending axis is slidable, pressed together, and there is · pressure on the back of the piston plate to vary the compression exerted on the separation device; the front plate of the bracket is provided with holes through which the inflows and outflows of the membrane filter device pass; the bracket points a back plate located behind the piston plate, which is sealed with the piston plate via a membrane is connected to form a pressure chamber between the back plate and the piston plate, the back plate is firmly connected to the front plate, so that pressure rises in the / pressure chamber "2ftf ~ erreT ~ 1iompression of the piston lying between the piston plate and the front plate lead device; the geometry of the flow channel is varied depending on changes in a control parameter the separator :; the control parameters. is the pressure drop at the inlet and outlet of the Channel for the particle mixture; Means are provided to reduce the pressure drop,. Between the inlet and the Outlet of the channel to measure the particle mixture, the Throughput of the particle mixture on entry into the separation device to. determine and a proportional

Relationship between the pressure drop and the throughput of the Particle mixing by changing the height of the channel for the Maintain particle mixing; the proportional relationship between the pressure drop and the .throughput of the Particle mixing is maintained as long as the pressure drop is below a predetermined level, and the pressure drop becomes greater as the throughput of the particle mixer increases above a value equal to the predetermined one Level of the pressure drop is maintained at "this level; the pressure drop across the membrane is held at a predetermined level by the fact that. adjusts the filtrate throughput; the inlet of the particle mixture is connected to a line coming from a patient, and -the concentrated particle mixture that leaves the device is returned to the patient along with a replacement fluid; the particles are formed elements; the filtrate is Plasma.

The invention also provides a holder for supporting and compressing a membrane separation device, the has a channel for a particle mixture and a filtrate channel, between a front plate and a piston plate, which is displaceable along an axis extending transversely to the plates, the holder also being a pressure device which changes the pressure applied to the rear side of the piston plate in order to the compression of the separation device and the geometry of a flow channel arranged in this to vary. Preferred embodiments are characterized in that the front plate has holes, through which the inflows and outflows of the separation device pass, the holder also having a back plate is provided, which is sealing via a membrane

connected to the rear surface of the piston plate to a pressure chamber between the back plate and the piston plate to build.

The invention also provides a separation device with a membrane inside a housing to form a channel for a particle mixture and a fluid channel. The device delimiting the filtrate channel forms a throttle point within the channel, so that caused by the filtrate flow, there is a pressure drop across the filtrate flow path. This represents represents a passive reduction in the changes in pressure drop across the membrane occurring along the membrane, thereby greater velocity gradients in the flow channel for the particle mixture and, accordingly, a larger flow along the membrane will be allowed. Preferred embodiments are characterized by the following features characterized: The flow restrictors comprise devices with V-shaped, directed against the membrane Grooves that form V-shaped channels, their upstream Sections are shallower than the downstream sections; alternatively, the flow restrictors. Include facilities with a surface, the roughness' along the filtrate channel is large enough to to allow a flow between the surface and the membrane, but on the other hand small enough to achieve the desired Create pressure drop; Furthermore, the flow limiter can consist of a flow resistance inserted into the filtrate channel consist (for example of a fabric or of fiber material); there are a plurality of Membranes and a plurality of devices for delimiting filter channels, flow channels for the particle mixture and piltrate channels provided, the devices for delimiting the filtrate channels from parallel

lelen panels are made; the case and the microporous Membranes can change the geometry of the flow channels for change the particle mixture, specifically as a function of an external force acting on the housing; the change in geometry is a change in height; the housing includes a spacer plate, which is sealed in Contact with the microporous membrane is.

The invention also provides a separation device with a membrane, which is arranged in a housing, around a channel for a particle mixture and a Form filtrate channel. When an external force acts on the housing, there is a change in the Geometry of the channel for the particle mixture. The case and the membrane also forms inlet and outlet conduits for the particle mixture that are large enough to to cause associated pressure drops, the latter are small enough to determine the pressure drop in the flow channel for the particle mixture in that Measurements are carried out in external lines that are connected to the inlets and outlets. Preferred Embodiments are characterized in that a plurality of membranes and a plurality of devices are provided which limit the filtrate channels, filter channels and flow channels for the particle mixture, wherein the means delimiting the filtrate channels are parallel plates; further comprising the housing a spacer plate in sealing contact with the microporous membrane; and finally the change in geometry is a change in height.

Furthermore, the invention creates a separation device with a channel for a particle mixture and with a

BATH ORIGINAL

Filtrate channel, which is bounded by a membrane that . seated between an apertured plate and an end plate. The plates are on the perimeter with each other welded, and the device may have a change in the geometry of its channels for the particle mixture or their piltrate canals as a function of an external force acting on the device. Preferred Embodiments are characterized by the following features: There are a plurality of plastic membrane holding plates between the plate provided with openings and the face plate and a plurality of channels for the. Particle mixture, piltrate channels and membranes are provided, the plates being welded to one another at the periphery are; between each pair of membrane retaining plates there are two membranes; a spacer plate forms a seal with respect to at least one membrane; the The device can cause a change in the height of the channels for the particle mixture, depending on from an external force acting on the apertured plate and the face plate.

According to a further feature of the invention is a separation device created having a membrane which is arranged within a housing to a Channel for a particle mixture and a filtrate channel · The housing includes a resilient spacer plate in sealing contact with the membrane, for a decrease in the height of one of the channels; evoke when the spacer plate is compressed. Preferred embodiments are characterized in that a plurality of membranes., Filtratkanäle and 'channels are provided for the particle mixture and that the housing a Comprises a plurality of parallel plates, the channel for the particle mixture being of a pair of membranes

is bordered by an elastic spacer are separated from each other.

The invention also provides a separation device with a pair of microporous membranes disposed within a housing, around a Flow channel for a particle mixture between the To limit membranes and a pair of filtrate channels, each filtrate channel being limited on one side by a membrane. By using two membranes to limit the channel for the particle mixture causes both large sides of the channel for the particle mixture to be actively involved in the deposition of the Participate in piltrats. In a preferred embodiment, a plurality of membranes are filtrate channels and channels for the particle mixture provided, the housing comprising a plurality of parallel plates.

Further advantages and features of the invention emerge from the following description of preferred exemplary embodiments in connection with the accompanying drawing. The drawing shows in:

Pig. 1 is a schematic representation of a blood cell separator according to the invention ;.

2 shows a perspective view of a separation device and a holder of the device according to Fig. 1;

3 shows a vertical section through the holder 2, along the line 3-3 in Fig. 2; ■

Pig. k shows a horizontal section through the holder along the line 4-4 in FIG. 3;

Fig. 5 is an exploded perspective view of the separating device;

Figure 6 is an exploded perspective view of a set of channels of the separator;

7 shows a schematic vertical section through part of the set of elements according to FIG. 6;

Fig. 8 is a schematic vertical section through the element set according to FIG. 6, namely after compression the separator;

Fig '. Figure 9 is a block diagram of control electronics for the system of Figure 1;

10 shows a vertical section along line 10-10 in FIG. 6j, but through a modified embodiment of a plate element of the separation device according to FIG. 5.

Fig. 1 shows a plasmapheresis device 10 for separating plasma (small blood components, including Immune bodies, albumins and other proteins) from the "formed elements" (red blood cells, white blood cells and platelets) from a patient's blood and for reclamation of the shaped elements together with balancing fluid to the patient. This method has a wide range of uses, including for the therapeutic removal of pathological ones Substances found in the plasma portion of a patient's blood. The device 10 includes a

BATH ORIGINAL

Blood inlet line 12 and a blood return line 14 connected to lines which are in communication with the patient. The Eirilaß line 12 contains a pressure sensor 15 with an associated drip chamber 17 upstream of a peristaltic blood pump 16 for monitoring the blood pressure in this inlet line 12. A feed line (not shown) for an anticoagulant is also connected to the latter. Downstream of the blood pump 16 there is a blood inlet drip chamber 18 with associated pressure sensor 19. A separating device 20 for shaped elements has a blood inlet opening 22 (for receiving all of the patient's blood), a blood outlet opening 26 and a plasma piltrate opening 28. The blood inlet opening 22 is connected to the outlet of the drip chamber 18 via a line 24. The plasma piltrate opening 28 is connected via a line 30 to a plasma drip chamber 32, a peristaltic plasma pump 34 and a plasma collecting vessel 36. The plasma drip chamber 32 is provided with an associated pressure sensor 37. The separating device 20 sits within a clamping bracket 38, which will be described in more detail below and which compresses the separating device 20 in order to vary the height of the blood channels contained in the latter, with the aid of a pressure which is supplied by a pressure source 40 . The latter consists of a pressure chamber with a piston that is driven by a spindle, which in turn is connected to a control motor. The bracket 38 weist- a valve to ¹ Il, which serves for blowing off air. The blood outlet opening 26 is connected via a line 42 to a connection piece 44 to which replacement fluid is supplied from a reservoir via a peristaltic pump 48. The connection piece 44 is connected to a return drip chamber 43 via a line 47

323 631Q

connected, which has an associated pressure sensor 50. The outlet of the drip chamber 43 is to an air bubble detector 52 and connected to the return line 14 leading to the patient.

FIG. 2 shows the separating device 20 arranged within the clamping holder 38. The openings 22, 26 and 28 extend through holes in a faceplate 54 that are vertically slidable between side supports 56 and 57 seated. The separating device 20-becomes from a piston plate 58 in contact with the faceplate 54 held, the piston plate 58, as shown, in part extends beyond a cover plate 60.

From Fig. 3 it can be seen that the. Piston plate 58 carries circular piston projections 62 and 64 which protrude from the rear of the piston plate. Roller diaphragms 66 and 68 are connected to the piston projections 62 and 64 by means of screws 70 and 72 and circular retaining elements 74 and 76, respectively. At their circumference, the membranes 66 and 68 are clamped between caps 78 and 80 and the inner surface of a rear plate 82 in a sealing manner. The rear plate 82 has cylindrical recesses 84 and 86 for receiving the two piston projections and their associated holding elements. A female connector 88, which serves as part of a universal joint and is used for connection to the pressure source 40, is connected to the recess 86, while the air vent valve 41 is connected to the recess 84. A channel 90 creates a connection between the recesses 84 and 86.

From Fig. 4 it can be seen that the front plate 54 is a

Has pair of V-shaped grooves 92 into which V-shaped projections 94 fit, extending from transverse extensions the side supports 56 and 57 extend rearward. Pins 96 protrude from the side supports 56 and 57 inward, with their free ends in vertical Grooves 98 engage, which run along the side edges of the faceplate 54. As shown, protrude Sections of the cap 78, the perimeter of the diaphragm .66 and the associated circumference of the rear plate, 82 in recesses 100 and 102 - of the side supports 56 and 57 into it.

Fig. 5 shows an exploded view of the separation device 20. The blood inlet opening 22, the blood outlet opening 26 and the plasma filtrate opening 28 sit on the front of an orifice plate 104 made of plastic. Between the orifice plate 104 and a back plate I06 there are six sets 108 of plasma-blood-plasma channels, wherein in Fig. 5 only three sentences are shown. Each set IO8 includes two membrane support plates 110, two made of plastic existing microporous membranes 112 (which have a thickness of about 0.17 mm and a mean pore size of about 0.6 Microns), as well as a spacer plate 114 lying between the membranes 112 and having a thickness of approximately 0.1 mm. Adjacent sets IO8 of the plasma-blood-plasma channels have a membrane support plate 110 in common. Fig. 6 shows the support plates, the membranes and the. Spacer plate, belonging to a channel set 108. Blood channels B lie between the membranes 112, and Plasma channels P between the membrane support plates 110 and the membranes 112. Each membrane support plate 110 is made of acrylonitrile butadiene styrene (ABS) and is approximately 2.9 mm thick, 222 mm long and 83 mm wide. Holes II6 in the

Support plates 110 and holes 130 in the membranes 112
are aligned with the inlet opening 22 in order to guide the inflowing blood from the inlet opening 22 into all of the blood channels B of the channel set 108. Holes 118 in the support plates 110 are equally aligned with the blood outlet opening 26 and with holes 132 in the membranes 112,
the concentrated mixture of shaped elements
flow from the blood channels B to the outlet opening 26
permit. Holes 120 in the support plates 110 are aligned
the plasma filter opening 28 and with holes 134 in the membranes 112 so that the plasma can flow from the filtrate plasma channels P to the plasma filtrate opening 28.

A plurality of V-shaped, elongated grooves 122, which are separated from one another by three parallel webs 124, are provided on the upper and lower surfaces 123 of the support plates 110. Around the scope of the
The upper and lower surfaces 123 of the support plates 110 run uninterrupted sealing edges, including the holes 116, 118 and 120 and the grooves 122. Each sealing edge has a semicircular cross-section with a radius of about 0.1 mm and protrudes over the
Level of the upper or lower surface 123 of the support plate 110 also. As can be seen from Figures 7 and 8, the sealing rims 126 are on the top and bottom
Faces not aligned. Similar uninterrupted sealing rims 133 on the support plates 110 surround the holes 120. The V-shaped grooves 122 are defined by
Faces formed at an angle of 45 ° to the
Areas 123 stand. The V-shaped grooves 122 are approximately 1 mm wide and 0.5 mm deep. Tips 125 of the plate sections between adjacent grooves 122 (FIGS. 7 and 8) are approximately 0.07 mm above or below the surfaces 125. The surfaces of the webs 124 are on the same level

ORIGINAL

32363 ΊΟ

Plane with the surfaces 123. The grooves 122 end near the Outlet hole 120 in a transverse plasma outlet channel 128, which collects the plasma from the grooves and directs it to an L-shaped channel 129, which is below the sealing edge 133 and is between the surfaces 123 with the interior of the hole 120 in communication. On the narrow sides of the support plates 110 are openings 180 and protrusions 182 provided, which mate with corresponding protrusions and openings of the adjacent plates to a Alignment during assembly.

Once assembled, the portions of membranes 112 surrounding holes 130 and 132 are heat sealed to the opposing surfaces of support plates 110, to seal the blood inlet and outlet manifolds to surrender and one crosses between the blood and to prevent plasma channels. The support plates 110, the membranes 112 and the spacer plates 114 'are brought together. The sealing edges 126 create a good seal between the spacer plates 114, the membranes 112 and the support plates 110. The peripheral areas of the support plates are welded together so that the molten material ABS of adjacent support plates 110 mixed. As best seen in Figures 7 and 8, the edges of the membranes 112 and the spacer plate lie Il4 within the edges of the support plates 110. At the ends of the stack, a Mixing of the plastic material of the orifice plate 1.04 and the back plate '106 with that of the adjacent support plates 110 so that the entire stack is connected to one another and sealed to form separator 20. The portions of the membranes 112 that make up the Surrounding holes 134 are formed by the uninterrupted sealing edges 133, which on the surfaces of the support plates 110 around

BATH ORIGINAL

- ψ- ZZ,

are provided around the holes 120, squeezed together to form plasma outlet channels which are sealed against the blood outlet channels, namely the holes 118. For reasons of simpler manufacture and assembly, holes 135, cross-running .Kanäle 139, L-shaped channels 137 and 110 are also on the inlet side of the support plates. Sealing edges 14l (similar to the holes 120, the transverse outlet channels 128, the L-shaped channels 129 and the sealing edges 133) are provided, but there is no opening corresponding to the filtrate opening 28 at this point. The pla-sma collected in the V-shaped grooves 122 is thus directed into the holes 120 which are connected to the plasma piltrate opening 28. _:

The orifice plate 104, the back plate 106, the membrane support plates 110 and the spacer plate II4 together form a housing which, together with the microporous Membranes 112 define the plasma and blood passages.

A blood inlet manifold, which distributes the blood from the inlet opening 22 to the blood channels B, is formed by the holes 116, the membranes 112, the holes 130 and the semicircular and triangular depressions in the surfaces of the support plates 110 around the Holes 116 are formed. A blood outlet manifold is similarly created by the holes 118 ', the membranes 112, the holes 132 as well as the semi-circular and triangular depressions lächen ⁿ in the B of the base plates are formed around the holes 118 around 110th Both of these collecting lines are large enough to generate a pressure drop which is sufficiently smaller than the pressure drop along the blood channels B to be able to determine a pressure change along the blood channels by the fact that the pressure in

BAD ORIGINAL; ^

external lines attached to the blood inlet port and outlet opening "are connected.

In operation, the Blut-Eilaßleitung.12 and the Return line 14 connected to the patient Blood travels through the inlet line 12, the Blood pump 16 and the line 24 to the inlet port 22 of the Separator 20. The blood flows through the holes 116 of the support plates 110 and through the holes 130 of the Membranes 112 and enters the blood channels B between the membranes 112. Since the sections of the membranes 112, which surround the holes 130 are sealed with the opposite portions of the support plates 110 surrounding the holes 116, the entering blood can only pass through the membranes 112 to their plasma sides which are opposite the support plates 110.

Normally the pressure in the B blood channels is higher than the pressure in the plasma channels P on the other sides of the membranes 112. This causes the membranes 112 are pressed against the tips 125 of the support plates 110, whereby the blood channels B are formed. Those components of the blood which are smaller than the pores of the membranes 112 pass through the latter and flow along the V-shaped grooves .122 and the opposite surfaces of the diaphragms 112, whereupon they to the transverse outlet channel 128, the L-shaped channel 129 and reach the plasma outlet hole 120 in the support plate 110. Due to the pressure seal between the sealing edges 133 and the openings 134 surrounding sections of the membrane 112, there is no leakage loss between the plasma channels P and the blood channels B.

The shaped elements that are larger than the pores in the Membranes 112, and the other components that do not pass through the membranes, flow through the blood outlet holes 132 of the membranes and through the holes in the support plates 110; Here, too, prevents the seal between the sections of the membranes 112 that make up the holes Surrounded, opposite the portions of the support plates 110 that surround the holes 118, leakage losses of the molded Elements in the direction of the plasma channels P. In the support plates 110, in the portions surrounding the holes 116 and 118, is a stepped depression formed, and the pressure of the blood presses the corresponding portions of the membrane 112 against the support plates 110. The transverse exit channels 128 are narrow enough and the membranes 112 are stiff enough to block the exit channels 128 at the pressures applied through the membranes to prevent.

According to Pig. 1 the plasma filtrate flows out of the piltrate opening 28 through line 30, drip chamber 32 and the plasma pump 34 to the collecting vessel 36. The concentrated mixture of the shaped elements passes from the outlet opening 26 through the line 42 to the connector 44, where replacement fluid from reservoir 46 is added. The make-up fluid from reservoir 46 becomes the connector 44 supplied by the pump 48 in a controlled amount, depending on the particular circumstances of the patient and from the control electronics of the pump 48. For example, the supply of the compensating fluid faster than the plasma drainage, if you want to supply the patient with excess fluid, for his Keep blood pressure high and avoid those problems associated with low blood pressure. In certain cases, the supply of the compensation fluid

also take place more slowly than the plasma discharge. The concentrated mixture of the shaped elements flows together with the replacement fluid through the line kl i, the drip chamber kj>, the air bubble detector 52 and the return line Ik, whereupon it reaches the patient.

During the plasmapheresis, the blood pump 16 is operated so that that it pumps the blood at the desired rate. Often it is the maximum speed, which can be achieved without harming the patient or the blood vessel from which the blood is drawn is taken to collapse. The shear or shear rate (shear rate) can then thereby at a desired level (namely, large enough to prevent pore clogging, but small enough to to avoid hemolysis) by removing the Height between the membranes 112, that is to say the height of the blood channels B controls. This is done by having the separation device 20 compressed by means of the holder 38,

The following equation gives the shear SR for a fully developed flow of a Newtonian fluid in a right-angled channel, the width of which is sufficiently large compared to the height to accommodate the end or To be able to neglect edge effects:

2/3

(1)

H ² w ¹ W-. I 12 and 1

Herein, means:

Q = flow rate of the fluid in the right-angled channel

w = width of the channel

H = height of the duct

1 = length of the channel

&? - pressure loss along the channel *

u = viscosity of the fluid.

From the first equivalent of equation (1) it follows that the shear is directly proportional to the blood flow rate and is inversely proportional to the square of the height H of the duct. The second equivalent of equation (1) shows that the Pressure loss along the channel depends on the shear and the channel height and is therefore a measure of this.

7 shows the blood channel B at low pressure from the pressure source 40 and a relatively high blood throughput. Fig. 8 shows the blood channel with the blood flow rate reduced to such an extent that the channel height H must be reduced in order to be below it new conditions to maintain the desired shear. It does this by increasing the pressure from the Pressure source 40, from which an increased pressure between the rear plate 82 and the piston plate 58 results. Latter thus migrates to the right in Fig. 4, whereby the separating device 20 between the piston plate 58 and the front plate 54 is compressed. Part of the compression is received by the membranes 112 and part of the spacer plates 114 and the plastic support plates 110. Since the membranes 112 are already supported by the tips 125, changes in the thickness of the separator result 20 to changes in the height H between the membranes 112. These changes in height are recorded in the apparatus 10 controlled by monitoring and controlling the pressure drop across the B blood channels. ■.

Pig. 9 shows control electronics ΐβΟ for carrying out a certain process sequence during operation of the device 10. After this process sequence, the height H is varied such that a pressure drop Δ P between the inlet opening 22 and the outlet opening 26 in accordance with the following equations (2) and (3 ) results in:

- v - ⁽²⁾

P = [1.CLmm Hg / ml / minJ χ Q _ß for ² IO Z. Qg £ 100 ml / min

P = 100 mm Hg 'for 160> Q _n > 100 ml / min

_{Q R} therein denotes the total blood throughput entering the separation device 20.

The differential pressure TMP across the membranes, i.e. from side to side, near the outlet end of the membranes 112 is maintained at 25 mm Hg, unless the plasma rate Q _p increases in an attempt to reach the TMP value of 25 mm Hg 0.6 Q _ß . For this case, Q _{p is} limited to 0.6 Q _B. The value of 25 mm Hg applies to the differential pressure TMP at the outlet end because this results in a flow through the membranes 112 which is acceptable. At the same time, the differential pressure near the inlet end is at or below 125 mm Hg. This value is not high enough to lead to hemolysis or to clogging of the pores. The pressure in the plasma channels P remains essentially constant over their length.

When the method sequence described above is being carried out, a 4 P control signal generator 162 receives signals from the blood pump 16 which _{reflect the total blood throughput Q rt} entering the separation device 20. Of the

B. Control signal generator provides a control signal ^ j P ¹ that the

the desired pressure drop along the blood channels B

speaks to a comparator ΐββ. A subtraction circuit 164 receives signals from the pressure sensor 19 which indicate the pressure at the inlet opening 22 of the separation device 20. Furthermore, this subtraction circuit receives signals from the pressure sensor 50 which reflect the pressure of the concentrated mixture of the shaped elements, namely when they emerge from the blood channels B through the outlet opening 26. The subtraction circuit 164 supplies a signal β. P, which represents the actual pressure loss along the blood channels B, to the comparator 166. If the signal A P ^f equals the signal AP, the comparator 166 applies a signal to the motor of the pressure source 4o which means that the pressure in the Holder 38 should be kept at the current value in order to also maintain the height H in the blood channels B at the current size.

When the signal ^ P ^f exceeds the signal ^ P by more than a predetermined amount, the comparator 166 sends the motor to the. Pressure source 40 such signals that the pressure in the holder 38 is increased in order to reduce the height H and the actual value Δ P of the pressure loss to the nominal value J ^. Let P ^f increase. If 2} P 'is less than Δ P by a predetermined value, the signals supplied by the comparator 166 to the motor of the pressure source 40 drop the pressure in the holder 38 in order to cause the height H in the blood channels B to be increased. The pressure source 40 is monitored and controlled in such a way that certain safety pressure limits in the holder 38 cannot be exceeded.

A subtraction circuit 168 receives signals from the pressure sensor 50 which determine the pressure in the concentrated mixture of the shaped elements as it exits the

Indicate blood channels B through outlet port 26. Furthermore, this subtraction circuit receives signals from the pressure sensor 37 which reflect the pressure of the plasma in the separation device 20. The subtraction circuit 168 provides signals TMP indicative of the actually prevailing membrane differential pressure near the outlet of the separating device 20. An 0-control signal transmitter 172 (0 is defined as Q _p / Q _B) receives signals from the blood pump 16 to the separator 20 · Show the incoming blood flow Q _R. In addition, this control signal transmitter receives signals from the plasma pump 3 ^ which reproduce the plasma flow rate Qp which passes through the membranes and exits from the separating device 20. The control signal generator applies a control signal GS to a TMP signal modifier 170. As soon as Q _p approaches the value 0.6 Q _β , the TMP signal modifier 170 is informed accordingly by the control signal CS. The signal modifier then acts on the drive of the plasma pump in such a way that Q _p does not exceed the value 0.6 Q _R. If Q _p does not approach 0.6 Q _n , the TMP signal modifier 170 causes the plasma pump 34 to operate such that the desired value TMP is obtained.

Modified embodiments are within the scope of the invention. For example, it must have the shaped elements The mixture containing it does not consist of blood as a whole, as is the case with the plasmapheresis described above is. The mixture may contain red blood cells, white blood cells, and / or platelets that are from whole blood Blood was separated and frozen in an electrolyte solution. Likewise, the invention is not limited to that Deposition of such shaped elements is limited. Rather, it can also be used for deposition of bacteria or other cell cultures (for example

BATH ORIGINAL

Liver cells), which one does not want to destroy during the separation process, as well as the separation of precipitation products or other particles, the size of which exceeds the pore size, from liquid mixtures of the particles.

In addition to varying the height of the channels, their Geometry can be varied by changing the width (from equation (1) it follows that the Shear with both the height and the width of the right angle Channel changes) or the shape of the channels. For example, you can use the sides of a separator Press together to increase the duct height and reduce duct width. Movable partitions can also be used provide in order to variably limit the flow channels.

The geometry of the channels for the particle mixture (e.g. blood channels B) can be varied uniformly over the channel length, depending on other control parameters in addition to or instead of maintaining a proportional relationship between the pressure drop A- P along the channel for the particle mixture and the throughput entering that channel as described above. Other procedures can lead to one of the following operating conditions being made control parameters: the pressure drop along the channels for the particle mixture, the pressure drop along the filtrate channels, the throughput of the particle mixture, the particle concentration, the differential pressure measured across the membrane or the flow. ■

The geometry of the channels can also be actively or passively varied over their length. the deposition as a function to optimize dos location over the length of the membranes.

This is desirable because the throughputs and the particle concentrations are different at different points along the membranes and because the optimum parameters for achieving the desired rate of piltration while avoiding clogging and particle destruction depend on these different throughputs and particle concentrations. These parameters are, for example, the differential pressures measured across the membranes, the velocity profiles (across the membranes) and the particle concentration profiles (also perpendicular to the membrane). One way of achieving this optimization is to actively vary the geometry of the channel for the particle mixture over the entire length of the channel, depending on the operating conditions, such as the throughput of the particle mixture, the particle concentrations, the flow, the pressure drop along the channel for the particle mixture, the pressure drop along the piltrate channel, the membrane differential pressure profile along the membrane, the velocity profile in the particle mixture and the concentration profile in the particle mixture. The operating conditions used in each case form the control parameters for the process sequence. One way of acting on at least some of the desired results is to passively vary the geometry of the piltrate canal so that a desired pressure gradient is established along the piltrate canal, as will be described in more detail below. The geometry of the Piltrat canal can also be actively varied depending on the operating conditions. (One way to change the geometry of the piltrate canal is to use an accordion-like element to form the V-shaped grooves that can be expanded or contracted.) Changes in the geometry of the piltrate canal cause changes

in the filtrate pressure, whereupon the TMP value changes, which in turn affects the operating conditions in the channel for the Particle mixture influenced. The desired pressure gradient in the filtrate channel represents that gradient accordingly represents the preferred TMP value in connection with the pressure gradient in the channel for the particle mixture and specifies other operating conditions. The geometry changes in the channel for the particle mixture and in the Piltrate canals can be used together or independently.

There can be flow resistances in the filtrate flow paths Insert between the membranes and the support plates. This allows pressure drops to pass along in a passive manner achieve the filtrate flow paths linked to the pressure drops come along the flow paths for the particle mixture. Correspondingly, one can use higher speed gradients Apply in the flow channel for the particle mixture, resulting in a higher flow along the whole Length of the membrane allows. The mentioned flow resistance can be caused by the fact that the V-shaped grooves at the upstream end which the throughput is lower, makes it flatter, as shown in FIG. You can also use a flow resistance cause by using instead of the V-shaped grooves a surface roughness that is large enough to allow flow but small enough to produce the desired pressure drop. Flow obstacles, such as fabric or fiber material, can also be placed between the membranes and the membrane support plates insert. Furthermore, the flow resistance can be such that instead of a pressure drop, which the pressure drop in the flow channel for the particle mixture approximates, selects the pressure drop so that the TMP value

along the membrane depending on the concentration of the shaped elements or depending on others Operating conditions changes.

In addition, the differential pressure measured across the membrane can be maintained by the fact that the flow the particle mixture and, in addition, the operation of the piltrate pump varies. A change in the differential pressure can be brought about by changing the height of the channels for the particle mixture. Other microporous Membranes can be used in the same way. Furthermore, one can dispense with the spacer plates 114, thereby ensuring the desired depth of the blood channel, - that one Tips 125 of the V-shaped grooves 122 are lowered relative to the surfaces 123.

The separator 20 may contain any number of sets 108 of plasma blood plasma channels. It can even have only a single plasma channel, which is separated from a blood channel by a single membrane. If only a single set 108 of plasma-blood-plasma channels is to be used, the membrane support plates 110 are superfluous. The V-shaped grooves for supporting the membranes can be formed on the inner surfaces of the orifice plate 10 and the back plate ¹ I 106th These plates can be welded together in the same way as the adjacent support plates 110 according to FIGS. 7 and 8 are welded together,

The Abseidevorrichtung 20 can not only between the Front plate 54 and the piston plate 58 compressible but it can also be attached to these plates, in which case a vacuum is applied to the wells 84 and 86 can apply to the separator 20 so to

stretch so that the height H of the blood channels B changes.

There is also the possibility that the entire separating device does not have to be compressed. Between the orifice plate 104 and the back plate 106 a bellows-like device can be arranged to hold the remainder of the housing (namely the spacer plates 114, to compress the support plates 110 and the membranes 112) and thereby the height of the channels for the particle mixture to change.

Instead of the spacer plates 114 made of polyethylene of 0.1 mm thickness, a thicker spacer plate or one made of elastic material, for example rubber, can be used to make the device more resilient to design and to allow major changes in the height H of the channels.

Blank page

Claims (1)

COBE Laboratories, Inc. "11,283 1201 Oak Street Lakewood, Colorado 80215 ■ Claims 1. . Device for separating a liquid FiI-Trats, that no particles above a predetermined one Size, from a liquid particle mixture, marked by a housing (104, 106, 110) with an inlet (22) for the particle mixture, an outlet (26) for the particle mixture and a filter outlet (28); by a microporous membrane (112), the pores of which have the predetermined size and which are inside of the housing is arranged around a flow channel (B) for the particle mixture and a filtrate channel (P) define each channel of which one of its sides is bounded by the opposite sides of the membrane will; wherein the flow channel (B) is in communication with the inlet (22) and the outlet (26) for the particle mixture stands, while the filtrate channel (P) is connected to the Filtratauslaß (26); and through a facility for actively varying the geometry of the flow channel (B) for the particle mixture or the filtrate channel s- (P) during the operation of the device. - P - 2. Apparatus according to claim 1, characterized in that as a device for changing the channel geometry a device is provided which the channel height by pressing the housing together (104, 106, 110) changes. '' 3. Device according to claim 1 or 2, characterized in that the device for · Compression of the housing (104, 1.06, 110) is a holder (38) which has the following features: a Front plate (54) having a first contact surface engaging the housing; a piston plate (58) with a second contact surface engaging the housing and a pressure receiving surface, the piston plate along an axis extending transversely to the first contact surface is displaceable; a printing device (40) to change the acting on the pressure receiving surface Pressure; wherein the housing (104, 106, 110) is inserted between the front and piston plate and wherein a Changes in the pressure acting on the pressure receiving surface, the compression of the housing and the channel height varies. 4. Device according to one of claims 1 to 3 » characterized in that the front plate (54) has holes through which the inlet (22) and the outlet (.56) for the particle mixture as well as the Pass through the filtrate outlet (28). 5. Device according to one of claims 1 to 4, characterized in that - that the compression device a rear plate (82) on the side of the piston plate facing away from the front plate (54) - ('5S) - and that the rear plate (82) has a Membrane device (66, 68) sealingly with the pressure receiving surface the piston plate (58th) is connected to between the rear plate (82) and the pressure receiving surface to form a pressure chamber, the back plate (82) being fixedly mounted for movement along the aforesaid Axis away from the front panel (5 ^). 6. Device according to one of claims 1 to 5, characterized in that the channel geometry changing device comprises a device which, in response to changes in one or more Control parameter works. 7. Device according to one of claims 1 to 6, characterized in that the the channel geometry changing device varies the height of the flow channel (B) for the particle mixture and that the Control parameters of the pressure drop in this flow channel (B) is between the inlet (22) and the outlet (26) for the particle mixture. 8. Device according to one of claims 1 to 7, characterized in that the the channel geometry changing device comprises a control device which has the following features: a device (19, 50) for measuring the pressure difference between the inlet (22) and the outlet (26) for the particle mixture; means for measuring the flow rate entering the inlet (22); and a first comparator (166) to change the height of the channel (B) for the particle mixture, to maintain a relationship between the pressure differential and the flow rate of the mixture. 9. Device according to one of claims 1 to 8, by indicating that the relationship between the pressure difference and the throughput of the mixture is proportional and that the first comparator (166) in the Is able to maintain this ratio as long as the pressure difference is below a certain level is, and to keep the pressure difference at this predetermined level when the flow rate of the mixture is above that Value increases corresponding to this predetermined level. 10. Device according to one of claims 1 to 9, characterized by a second comparator (170) for maintaining the pressure difference between the liquid in the channel. (B) for the particle mixture and the liquid in the filtrate channel (P). 11. Device according to one of claims 1 to 10, characterized by a filtrate pump (3 * 0, which is connected to the piltrate outlet (28) in connection, and by a second comparator (170) for maintaining the differential pressure between the liquid in the outlet (26 ) for the particle mixture and the liquid in the filtrate outlet (28) at a predetermined level by adjusting the throughput of the filtrate pump (3 ¹ O · ' 12. Device according to one of claims 1 to 11, geke η η ζ eich η et through an inlet line (12) which connects the inlet (22) for the particle mixture to a line coming from a patient, through a connector (44 ), which is connected to the outlet (26) for the particle mixture, through a device (46, 48) for supplying replacement fluid to the connector and through a return line (14) which connects the connector (44) to a patient ORIGfNAL return line connects. 13. Device according to one of the claims. 1 to 12, characterized in that the particles red blood cells, white cells or thrombocytes and that the pores in the microporous membranes are smaller than these particles are. 14. Device according to one of claims 1 to 13, thereby ge ke η η "ζ e ic h'n e t that the particles are shaped elements and that the pores .in the microporous membranes are smaller than these shaped elements where the filtrate is plasma. 15. Device according to one of claims 1 to 14, characterized in that-the device for changing the channel geometry comprises means for expanding the housing (104, 106, 110). 16. Device according to one of claims 1 to 15, characterized in that the geometry can be changed along the length of the channel 17. Device according to one of claims 1 to 16, characterized gekenn.ze I net that the for the Substitute fluid provided device a device (48) which supplies the replacement fluid at a flow rate which depends on the flow rate of the filtrate at the piltrate outlet (28) deviates. 18. A method for separating a liquid filtrate which does not contain any particles above a predetermined size, from a liquid mixture of the particles, in particular for operating the device according to the invention, thereby characterized in that a separation device is used, which has the following features: a housing having an inlet and an outlet for the particle mixture and a filtrate outlet and one inside the housing arranged microporous membrane to define a flow channel for the particle mixture and a piltrate canal, each of which canal on one of its sides from the opposite sides the membrane is limited, the flow channel for the particle mixture with the associated inlet and outlet is in communication, while the Piltratkanal to the Filtrate outlet is connected; that the liquid particle mixture is supplied to the inlet; that in the flow channel a mean pressure is maintained for the particle mixture, which is above the mean pressure in the piltrate canal is located; and that the geometry of the flow channel for the particle mixture or the piltrate channel is varied. 19. The method according to claim l8, characterized in that the variation of the channel geometry, caused by 'compressing the housing 20. The method according to claim l8 or 19, characterized marked that for compression of the housing a 'bracket is used, the one Front plate with a first contact surface engaging the housing and a piston plate with a second on the housing engaging contact surface and a pressure receiving surface, wherein the piston plate is displaceable along an axis extending transversely to the first contact surface; that the housing between the front plate and the piston plate is set and that one acts on the pressure receiving surface BATH ORIGINAL Pressure varies to change the compression of the housing and the channel geometry. 21. The method according to any one of claims 18 to 20, characterized in that the front panel the holder has holes through which the inlet and outlet for the particle mixture and the PiI-entered outlet go through. ! . _ ■ 22. The method according to any one of claims 18 to 21, thereby g e k e η η ζ e ic h η e t that the bracket on the side of the piston plate facing away from the front plate has a rear plate which is sealingly connected to the pressure receiving surface via a membrane device is to form a pressure chamber between the rear plate and the pressure receiving surface, and that the rear plate is fixedly mounted to prevent movement along said axis away from the front plate. 23. The method according to any one of claims 18 to 22, characterized in - that the channel geometry is varied depending on the changes in one or more control parameters. 24. The method according to any one of claims 18 to 23, characterized in that when varying the channel geometry of the differential pressure between the inlet and the outlet for the particle mixture is measured, that one determines the throughput entering the inlet and that the height of the flow channel for the particle mixture is changed so that the ratio between the differential pressure and the throughput of the particle mixture preserved. • \ "*" "" * '"" 3 23 63T0 25.. Method according to one of claims l8 to 24, characterized in that the ratio according to claim 24 is proportional and maintained for so long is how the differential pressure below a before ' certain levels, and that the differential pressure is maintained at this predetermined level when the throughput the particle mixture increases to a value above that value, which the said predetermined Level corresponds. 26. The method according to any one of claims l8 to 25, characterized in that a filtrate pump is used, which is in communication with the filtrate outlet, and that the pressure difference between the Liquid in the outlet of the particle mixture and the liquid in the filtrate outlet at a predetermined level is kept by adjusting the flow rate of the filtrate pump adjusts. 27. Method according to one of Claims 18 to 26, characterized in that the inlet for particle mixing with one of a patient Coming line is connected that the outlet for the particle mixture is connected to a connector which is with a line leading to the patient is connected, and that the connector is supplied with an exchange fluid. 28. The method according to any one of claims l8 to 27, characterized in that the particle mixture Is blood, the particles are shaped elements and the filtrate is plasma. • 29. Method according to one of Claims l8 to 28, as a result, I can say that the substitute fluid is supplied with a throughput which differs from the throughput of the filtrate pump when discharging the filtrate. 30. The method according to any one of claims 18 to 29, characterized in that the varying ' the channel geometry is carried out by expanding the housing. . 31. The method according to any one of claims 18 to 30, characterized in that the channel geometry is changed over the entire length of the canal. 32. Holder for holding and compressing a device for separating a liquid piltrate, which does not contain any particles above a predetermined size, from a liquid mixture of the particles, in particular according to one of the preceding claims or for performing the method according to the invention, characterized in that the separation device (20) has a housing (104, 106, 110) and a microporous membrane (112) which is arranged within the housing in order to form a flow channel (B) for the particle mixture and a piltrate channel (P) ', wherein the flow channel (B) for the particle admixture is in connection with associated inlets and outlets of the housing, while the piltrate channel (B) is connected to a filtrate outlet (26) 'of the housing; and that the holder (38) has a front plate (5 * 0 with a first contact surface engaging the housing, a piston plate (58) with a second contact surface engaging the housing and a pressure receiving surface and a pressure device ( ¹ JO) for varying the pressure on the pressure receiving surface applied pressure, wherein the piston plate along a · BATH ORIGINAL is displaceable transversely to the first contact surface axis; wherein the housing (104, 106, 110) between the front plate (54) and the piston plate (58) with im The membrane (112) running essentially parallel to the front plate and the piston plate can be used and a change caused by the pressure device in the pressure acting on the pressure receiving surface die Compression of the housing and the geometry of the flow channel (B) for the particle mixture or the filtrate channel (P) varies. 33. Holder according to claim 32, characterized in that the inlets and outlets (22, 26, 28) from a common surface (104) of the housing (10'4, 106, 110) and that the front plate (54) Has holes for the passage of the inlets and outlets. 34. Holder according to claim 32. or 33, characterized in that the device for A rear plate generates the compression on the side of the piston plate (58) facing away from the front plate (54) (82) which is sealingly connected to the pressure receiving surface via a membrane device (66, 68) in order to a pressure chamber to be formed between the rear plate (82) and the pressure receiving surface and that the rear plate (82) is rigidly attached to prevent movement along said axis away from the faceplate (54). 35.Device for separating a liquid FiI-Trats, which does not contain any particles above a predetermined size, from a liquid mixture of the particles, in particular according to one of the preceding claims or for performing the method according to the invention, characterized by 'a housing (104, 106, - Ii - 110) with an inlet (22) and an outlet (26). for the particle mixture and with a filtrate outlet (28); one microporous membrane (.112), which is arranged inside the housing, around a flow channel (B) for the particle mixture to build; wherein the flow channel (B) -for the Particulate mixture communicating with the associated inlet (22) and outlet (26); and with one Device that works together with the microporous membrane on the flow channel (B) for the particle mixture opposite side forms a filtrate channel (P) and a flow resistance within this Filtratkanals creates to cause a pressure loss along the flow path of the filtrate and on this Wise passively the changes that occur across the membrane Differential Pressure (TMP) across the membrane to vary. 36. Apparatus according to claim 35 »characterized in that the device defining the filtrate channel (P) has V-shaped grooves (122) directed towards the membrane (112) 'in order to form V-shaped channels which are covered by the membrane - the depth of these grooves being shallower in the upstream sections than in the downstream sections to cause the pressure loss. 37- device according to claim 35, characterized in that the piltrate canal (P) defining a surface along the channel with a surface roughness that is large enough to allow a flow between this surface and the To allow membrane (112), but small enough to the Cause pressure drop. BATH ORIGINAL 38. Device according to claim 35, characterized in that within the piltrate canal (P) a flow obstruction is provided to cause the pressure loss. 39 .. Device according to claim 38, characterized in that the flow obstacle is a Piece of fabric material is. 40. Apparatus according to claim 35, characterized in that the flow obstacle Fiber material is 41. Device according to one of claims 35 to 40, characterized in that the housing (104, 106, 110) and the microporous membrane (112) changes in "the geometry of the flow channel (B) for the Can cause particle mixing, depending on the application of an external force to the housing. 42. Device according to one of claims 35 to 41, characterized in that a plurality of membranes (112), of devices for defining filtrate channels (P), of filtrate channels (P) and of flow channels (B) is provided for the particle mixture and that the devices for defining the filtrate channels consist of a plurality of parallel plates (110). 43. ■ Device for separating a liquid filtrate, which does not contain any particles above a predetermined size, from a liquid mixture of the particles, in particular according to one of the preceding claims or for performing the method according to the invention, thereby marked that a housing (10 4, 106, 110) with an inlet manifold (116) and an outlet manifold (118) for the particle mixture as well with a Piltrat outlet manifold (120) and, furthermore, a microporous. Membrane (112) are provided which are arranged within the housing to a flow channel (B) for the particle mixture and a flow channel (P) Form, with each channel on one of its sides through the opposite sides the membrane is formed; that the flow channel (B) for the particle mixture with the associated inlet and outlet manifolds (116, 118) communicating; that the Piltratkanal (P) to the filtrate outlet manifold (120) is connected; that the inlet and outlet headers (116, 118) are large for the particle mixture are enough to create a pressure drop that is sufficiently smaller than the pressure drop along the flow is the air flow channel (B) for the particle mixture in order to record the pressure change along the flow channel (B) for particle mixing through pressure measurements in external. nen lines to allow that to the manifolds are connected for particle mixing; and that the housing and the microporous membrane changes in the Geometry of the flow channel (B) for the particle mixture or the filtrate channel (P) can cause, namely depending on the application of an external force to the housing. 44. Apparatus according to claim 43, characterized in that a plurality of membranes (112), of filtrate channels (P) and of flow channels (B) are provided for the particulate mixture and that the housing comprises a plurality of parallel plates (110). 45 .-- Device riiroh f-.rireir, the preceding an BAD ORIOINAL - l4 -. Proverbs 'by' denote that the Housing (104, 106, 110) has a spacer plate (114) which is in sealing contact with the microporous Membrane (112) is standing. 46. Device according to one of claims 43 to 45, characterized in that the housing (104, 106, 110) has a spacer plate (Il4) which is in sealing contact with each of the microporous membranes (112). 47. Device according to one of the preceding claims, characterized in that the change the channel geometry is a change in height. 48.Device for separating a liquid FiI-Trats, which does not contain any particles above a predetermined size, from a liquid mixture of the particles, in particular according to one of the preceding claims or for performing the method according to the invention, characterized by a housing with a Orifice plate (104) having an inlet (22) and an outlet (26) for the particle mixture and a piltrate outlet (28), with a back plate (106) and with a porous membrane (112), which are arranged between the plates is to a flow channel (B) for the particle mixture and to define a piltrate canal (P) together with the components of the housing; where the; flow channel. (B) for the particle mixture 'with the associated Inlets and outlets (22, 26) is in communication, while the Piltratkanal (P) is connected to the Fiitratauslaß (28) is; and-wherein the peripheral areas of the plates are welded together. .-15 ■ - ■ - · "■■ · 49. Apparatus according to claim 48, characterized in that the housing has a plurality made of plastic membrane support plates (110.) and that a plurality of microporous membranes (112) are provided to with the components of the housing a plurality of flow channels (B) for the particle mixture and to form filtrate channels (P), the peripheral areas of the membrane support plates (110), the orifice plate (104) and the back plate (IO6) are welded together. . . 50./· Device according to claim 48 or 49 , characterized in that each flow channel (B) for the particle mixture is delimited by two membranes (112). · 51. Device according to one of claims 48 to 50, characterized by a spacer plate (H ¹ O, which forms an uninterrupted seal around the circumference of at least one of the membranes (112). 52. Device according to one of claims 48 to 51 , characterized in that a change in height of each of the flow channels (B) for the particle mixture or each of the piltrate channels (P) is made possible, specifically as a function of the application of an external force to the orifice plate (104 ) and the back plate (106). · 53. Device according to one of claims 48 to 52, characterized in that the housing (104, 106, 110) has a device for generating a flow resistance in each of the piltrate channels (B). - ιβ - 54. Device for separating a liquid filtrate, which does not contain any particles above a predetermined size, from a liquid mixture of the particles, in particular according to one of the preceding claims or for performing the method according to the invention, characterized by a housing (104, 106 , 110) with an inlet (22) and an outlet (26) for the particle mixture and with a filtrate outlet (28); and by a microporous membrane (112) disposed within the housing to define a particulate admixture flow channel (B) and a filtrate channel (P), each of which is delimited on one side by the opposite sides of the membrane; wherein the flow channel (B) for the particle mixture with the corresponding inlets and outlets (22, 26) is in communication, while the filtrate (P) is connected to the filtrate outlet (28), and wherein the housing includes a spacing elastic plate ClI ¹ O in sealing contact with the microporous membrane (112) to cause a reduction in the height of one of the channels (B, P) when the spacer plate is compressed. . . 55. Apparatus according to claim 5 ^, characterized in that a plurality of membranes (112), of filtrate channels (P) and of flow channels (B) is provided for the particle mixture and that the housing a plurality of parallel plates (110) includes. 56. Apparatus according to claim 54 or 55, characterized g.ekennz e i.chne t that every flow channel (B) for the particle mixture is bounded by a pair of membranes (112). - 17 · - '■ 57 · Device for separating a liquid filtrate that contains no particles above a predetermined value Contains size, from a liquid mixture of the particles, in particular according to one of the preceding claims or for carrying out the method according to the invention, characterized by a housing (104, 106, 110) with an inlet (22) and an outlet (26) for the particle raising as well as with a filter outlet (28) and through a pair of microporous membranes placed within the housing, around a flow channel (B) for the particle mixture between the membranes and also to define filtrate channels (P) which are on one side of the membranes are limited; wherein the flow channel (ß) for the particle mixture with the associated inlets and outlets (22, 26) is in communication, while the filtrate channel (P) is connected to its filtrate outlet (28), 58. Apparatus according to claim 57 j- characterized in that a plurality of pairs of membranes (112), pairs of piltrate channels (P) and flow channels (B) are provided for the particle mixture and that the housing has a plurality of parallel plates (110). .59 · Method according to Claim 23, characterized in that the change in geometry is a change in height of the flow channel for the particle mixture and that the pressure drop is the control parameter is used in the flow channel for the particle mixture between its inlet and outlet. 60. The method according to claim 23, 59, .24 or 25, characterized in that the pressure »Ί Hf <* * - 18 - differentiated between the liquid in the flow channel for the particle mixture and the liquid in the "filtrate channel is maintained. 61. Device according to claim 23, 59, 24 or 25, gek.ennze thereby rejects that the particles are red blood cells, white blood cells or platelets and that the pores in the microporous membrane are smaller than these particles are. · ■ ' 62. Apparatus according to claim 48 or 49, characterized I don't deny that a change in geometry the flow channels (B) for the particle mixture or the filtrate channels (P) is made possible, depending on from the application of an external force to the separation device (20).