The present invention relates to a method and apparatus for the isolation, modification and re-administration of a molecule or biomolecule, or a class of biomolecules, from the body fluid of a mammal via an extracorporeal closed circuit device. The device is able to capture and modify the biomolecule by the covalent or non-covalent attachment of a secondary molecule or protein, by cross-linking the captured molecule, or by altering the structure of the molecule (for example, by deglycosylation, peptide cleavage, or aggregation). The apparatus can be used to return the modified molecule or biomolecule to the mammalian subject. The device and methods may be utilized for the patient-specific diagnosis and/or treatment of a disease state which presents an associated molecule or protein in plasma or any other fluidized physiological system. The methods and apparatus may also be employed as a closed system allowing the on-line purification and/or modification of a target molecule or biomolecule from a fluid source such as a bioreactor or perfusion bioreactor.

The present invention generally relates to systems and methods for targeted removal of a substance or biomolecule such as a protein from a biological fluid, such as blood. In some cases, the blood may be withdrawn from a subject, treated, and returned to the subject. Previous techniques for removal of biological materials from blood, such as hemodialysis and plasmapheresis, were generally non-specific (i.e., they removed a multitude of proteins/toxins from the blood). By contrast, novel methods and devices described herein are capable of removing specific or single substances such as proteins from biological fluids such as blood in a specific manner. Such highly specific protein removal has a broad array of clinical applications, including treatment of inflammatory conditions and autoimmune diseases.

The present invention concerns methods of treating a patient suffering from a traumatic brain injury (TBI), comprising contacting said patient's blood with a sorbent for an inflammatory mediator and kits for performing such treatments.

There are certain factors in the blood of pregnant women with pre-eclampsia that appear to be associated with the disease. These include a soluble variant of the fms-like tyrosine kinase receptor (sFlt-1), soluble Endoglin (sEndoglin), and Endothelin-1. There is also evidence that hypertension may be caused by Na/K ATPase inhibitors such as digitalis-like factor, ouabain-like factors, marinobufogenin and marinobufotoxin. This invention teaches the removal of multiple harmful factors using a combination of targeted apheresis and dialysis and/or ultrafiltration. Harmful factors that are proteins are bound out using immobilized binding agents such as antibodies, aptamers and binding peptides, while small molecule harmful factors are dialyzed out or filtered out. Removal of multiple harmful factors is expected to ameliorate the symptoms of pre-eclampsia and prolong pregnancy.

A cell processing system includes at least one processor connectable to a source container filled with a biological fluid, the processor including a spinning membrane configured to receive and separate target cells from the biological fluid, the target cells exiting at a first outlet, first and second containers selectively connected to the first outlet; and a magnet. The system also includes a controller configured to operate the spinning membrane to receive biological fluid and to direct the target cells to the first container, to pause to permit magnetic particles to be associated with the target cells in the first container, to operate the spinning membrane to receive the contents of the first container with the magnet applied to the target cells associated with the magnetic particles, to remove or deactivate the magnet, and to transfer the target cells to the second container.

A cell processing system includes at least one processor connectable to a source container filled with a biological fluid, the processor including a spinning membrane configured to receive and separate target cells from the biological fluid, the target cells exiting at a first outlet, first and second containers selectively connected to the first outlet; and a magnet. The system also includes a controller configured to operate the spinning membrane to receive biological fluid and to direct the target cells to the first container, to pause to permit magnetic particles to be associated with the target cells in the first container, to operate the spinning membrane to receive the contents of the first container with the magnet applied to the target cells associated with the magnetic particles, to remove or deactivate the magnet, and to transfer the target cells to the second container.

Systems and methods for cleansing blood are disclosed herein. The methods include acoustically separating undesirable particles bound to capture particles from formed elements of whole blood. After introducing the capture particles to whole blood containing undesirable particles, the whole blood and capture particles are flowed through a microfluidic separation channel. At least one bulk acoustic transducer is attached to the microfluidic separation channel. A standing acoustic wave, imparted on the channel and its contents by the bulk acoustic transducer, drives the formed elements and undesirable particles bound to capture particles to specific aggregation axes. After aggregating the particles, the formed elements exit the separation channel through a first outlet and are returned to the patient. The undesirable particles, bound to the capture particles, exit through a second outlet and can be discarded to saved for later study.

Blood treatment systems and methods are provided for combining a blood separation system and an adsorption device. The blood separation system is configured to separate a blood component from blood, while the adsorption device is configured to receive at least a portion of the separated blood component and process it. The blood separation system includes a fluid flow element and a controller. The fluid flow element is configured for flowing the separated blood component into the adsorption device. The controller controls the fluid flow element based at least in part on one or more processing parameters. The processing parameters include a maximum flow rate of the separated blood component flowed into the adsorption device, a maximum pressure of the separated blood component flowed into the adsorption device, and/or the volume of fluid in a location of the system.

Blood treatment systems and methods are provided for combining a blood separation system and an adsorption device. The blood separation system is configured to separate a blood component from blood, while the adsorption device is configured to receive at least a portion of the separated blood component and process it. The blood separation system includes a fluid flow element and a controller. The fluid flow element is configured for flowing the separated blood component into the adsorption device. The controller controls the fluid flow element based at least in part on one or more processing parameters. The processing parameters include a maximum flow rate of the separated blood component flowed into the adsorption device, a maximum pressure of the separated blood component flowed into the adsorption device, and/or the volume of fluid in a location of the system.

A column is disclosed for removal of sTNF-R2 from a body fluid. The column has a compartment, an inlet coupled to the compartment and configured to receive the body fluid, and a substrate disposed within the compartment. A capture ligand is coupled to the substrate and has a modified sequence with an amino acid substitution in a reference sequence that includes a portion of a natural TNF sequence. The modified sequence has an affinity for the sTNF-R2 that is greater than an affinity of the reference sequence for the sTNF-R2.