# US 6,099,730 A · Apparatus for treating whole blood comprising concentric cylinders defining an annulus therebetween

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- Number: US 6,099,730 A
- Document ID: US6099730A
- Status: Granted
- Kind: A
- Application number: 09/191,175
- Filed: 1998-11-13
- Granted: 2000-08-08
- Earliest claimed: 1998-11-13
- Assignees: Massachusetts Institute of Technology
- Inventors: Guillermo Ameer; Rober S. Langer, Jr.; Maria Rupnick; Hidde L. Ploegh; Eric Grovender
- Web page: https://patentgrep.com/patent/US6099730A

## CPC

- B01D 65/08: Prevention of membrane fouling or of concentration polarisation
- A61M 1/16: with membranes
- A61M 1/265: {inducing Taylor vortices}
- A61M 1/3437: {downstream of the filter, e.g. post-dilution with filtrate}
- A61M 1/3472: {with treatment of the filtrate}
- A61M 1/3475: {with filtrate treatment agent in the same enclosure as the membrane}
- A61M 1/3486: {Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents}
- A61M 1/3489: {by biological cells, e.g. bioreactor}
- A61M 1/3679: {by absorption (A61M1/3675 takes precedence)}
- A61M 1/38: Removing constituents from donor blood and {storing or} returning remainder to body {, e.g. for transfusion}
- B01D 61/00: Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor (separation of gases or vapours by diffusion B01D53/22)
- B01D 63/16: Rotary, reciprocated or vibrated modules
- A61M 1/3623: {Means for actively controlling temperature of blood}
- A61M 2202/0407: Lymphocytes
- A61M 2202/0415: Plasma
- A61M 2202/0421: Beta-2-microglobulin
- A61M 2202/0427: Platelets; Thrombocytes
- B01D 2321/20: By influencing the flow
- B01D 2321/2058: by vibration of the membrane, e.g. with an actuator
- B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28)
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}

## Abstract

Apparatus for removing substances from blood is disclosed. The apparatus includes concentric cylinders defining an annulus therebetween with the inner cylinder adapted for rotation with respect to the outer cylinder. At least one of the cylinders includes a porous membrane covered portion forming a compartment containing an immobilized active species. The active species is adapted to break down or remove the substance. Plasma in blood flowing in the annulus passes through the porous membrane and interacts with the active species either by reaction or binding. Red and white blood cells do not pass through the membrane. In this way, a substance is removed from plasma without exposing blood cells to the active species.

## Claims

### Claim 1

Apparatus for removing a substance from whole blood comprising:
concentric outer and inner cylinders defining an annulus therebetween, the inner cylinder adapted for rotation with respect to the outer cylinder;
at least one of an inner surface of the outer cylinder or an outer surface of the inner cylinder including a porous membrane covered portion forming a compartment containing an immobilized species, the species adapted to remove the substance;
an inlet for introducing blood into the annulus for flow along the cylinders; and
an outlet port for discharging the blood,
wherein the porous membrane allows plasma within the blood to interact with the immobilized species while restricting blood cells from interacting with the immobilized species.

### Claim 2 (depends on 1)

The apparatus of claim 1 wherein the rotation of the inner cylinder generates Taylor vortices in the annulus, the vortices creating oscillating pressure gradients within the annulus, the pressure gradients causing periodic undulations in the porous membrane resulting in circumferential flow in the compartment containing the immobilized species.

### Claim 3 (depends on 1, 2)

The apparatus of claim 1 or 2 wherein both inner and outer cylinders have membrane covered portions containing immobilized species.

### Claim 4 (depends on 1, 2)

The apparatus of claim 1 or 2 wherein the inner surface of the outer cylinder includes a recess covered by a mesh to exclude the immobilized species, the recess acting as a collection chamber for plasma after interaction with the immobilized species.

### Claim 5 (depends on 4)

The apparatus of claim 4 further including a pump for circulating plasma from the recess into the annulus.

### Claim 6 (depends on 1, 2)

The apparatus of claim 1 or 2 wherein the species is immobilized on agarose beads.

### Claim 7 (depends on 6)

The apparatus of claim 6 wherein the substance is heparin and the immobilized species is heparinase.

### Claim 8 (depends on 1, 2)

The apparatus of claim 1 or 2 wherein the substance is .beta..sub.2 M -microglobulin and the immobilized species comprises single chain antibody fragments.

### Claim 9 (depends on 8)

The apparatus of claim 8 wherein the apparatus is adapted to remove at least 0.2 g .beta..sub.2 M -microglobulin in a period of less than about three hours.

### Claim 10 (depends on 8)

The apparatus of claim 8 wherein the apparatus is adapted to remove at least 0.5 g .beta..sub.2 M -microglobulin in a period of less than about two hours.

### Claim 11 (depends on 8)

The apparatus of claim 8 wherein the apparatus has an active volume of less than about 350 ml.

### Claim 12 (depends on 8)

The apparatus of claim 8 wherein the apparatus has an active volume of less than about 200 ml.

### Claim 13 (depends on 8)

The apparatus of claim 8 wherein the apparatus has an active volume of less than about 50 ml.

### Claim 14 (depends on 1, 2)

The apparatus of claim 1 or 2 wherein the apparatus has a transmembrane flow rate of greater than about 50 ml/min.

### Claim 15 (depends on 1, 2)

The apparatus of claim 1 or 2 wherein the apparatus has a transmembrane flow rate of greater than about 100 ml/min.

### Claim 16 (depends on 1, 2)

The apparatus of claim 1 or 2 wherein the apparatus has a transmembrane flow rate of greater than about 200 ml/min.

### Claim 17 (depends on 2)

The apparatus of claim 2 wherein the immobilized species is immobilized on beads, and wherein the beads are fluidized by the circumferential flow in the compartment.

### Claim 18 (depends on 17)

The apparatus of claim 17 wherein the beads comprise a material selected from the group consisting of agarose, cellulose, and protein A.

### Claim 19 (depends on 1, 2)

The apparatus of claim 1 or 2 wherein the active species is in the form of micelles.

### Claim 20 (depends on 1, 2)

The apparatus of claim 1 or 2 wherein the inner cylinder rotates via magnetic coupling to an external motor.

### Claim 21 (depends on 12)

The apparatus of claim 12 wherein the inner cylinder rotates at approximately 1200 r.p.m.

### Claim 22 (depends on 1, 2)

The apparatus of claim 1 or 2 wherein the active species is selected from the group consisting of antibodies, antibody fragments, catalytic antibodies, enzymes, peptides, proteins, or living cells.

### Claim 23

Apparatus for collecting platelets from blood comprising:
concentric outer and inner cylinders defining an annulus therebetween, the inner cylinder adapted for rotation with respect to the outer cylinder;
at least one of an inner surface of the outer cylinder or an outer surface of the inner cylinder including two parallel porous membranes defining a first compartment therebetween and a second compartment between the membranes and the surface, the membrane closest to the surface having a pore size adapted to restrict the passage of platelets and the membrane farthest from the surface having a pore size adapted to allow the passage of platelets but to restrict the passage of other blood components;
an inlet for introducing blood into the annulus for flow along the cylinders;
means for removing platelets from the first compartment; and
an outlet port for discharging the blood.

### Claim 24

An apparatus for continuous treatment of a mixture comprising liquid and solid components, comprising:
concentric outer and inner cylinders defining an annulus therebetween, the inner cylinder adapted for rotation with respect to the outer cylinder;
at least one of an inner surface of the outer cylinder or an outer surface of the inner cylinder including a porous membrane covered portion forming a compartment containing a reactant for treatment of the liquid component of the mixture;
an inlet for introducing the mixture into the annulus for flow along the cylinders; and
an outlet port for discharging the mixture,
wherein the porous membrane allows the liquid portion of the mixture to interact with the reactant while restricting the solid portion of the mixture from interacting with the reactant.
