Systems and methods of blood-based therapies having a microfluidic membraneless exchange device

Abstract

The present invention is directed to devices, systems and methods for removing undesirable materials from a sample fluid by contact with a second fluid. The sample fluid flows as a thin layer adjacent to, or between, concurrently flowing layers of the second fluid, without an intervening membrane. In various embodiments, a secondary separator is used to restrict the removal of desirable substances and effect the removal of undesirable substances from blood. The invention is useful in a variety of situations where a sample fluid is to be purified via a diffusion mechanism against an extractor fluid. Moreover, the invention may be used for the removal of components from a sample fluid that vary in size. When blood is the sample fluid, for example, this may include the removal of ‘small’ molecules, ‘middle’ molecules, macromolecules, macromolecular aggregates, and cells, from the blood sample to the extractor fluid.

Description

CROSS-REFERENCE TO RELATED APPLICATION [0001] This application is a continuation-in-part of and claims the benefit of U.S. Ser. No. 10 / 801,366, filed Mar. 15, 2004 and a continuation-in-part of PCT International Application No. PCT / US04 / 07966, filed Mar. 15, 2004, and claims the benefit of U.S. Provisional Patent Application No. 60 / 454,579, filed Mar. 14, 2003, each of which is hereby incorporated by reference herein in its entirety.FIELD OF THE INVENTION [0002] Generally speaking, the present invention relates to the purification of a sample fluid. More particularly, the present invention relates to the purification of a sample fluid (e.g., blood fluid) by selectively removing components using a microfluidic membraneless exchange device. BACKGROUND OF THE INVENTION [0003] Extracorporeal processing of blood is known to have many uses. Such processing may be used, for example, to provide treatment of a disease. Hemodialysis is the most commonly employed form of extracorporeal process...

AI Technical Summary

Benefits of technology

[0014] Sheathing a core of blood with the miscible fluid, or assuring that the miscible fluid lies between at least a substantial portion of the blood and the enclosing boundaries of the flow path, prevents or at least limits contact of the blood with these boundaries. In turn, this configuration of the two fluids prevents or at least reduces the undesirable activation of factors in the blood, thereby minimizing bioincompatibilities that have been problematic in prior techniques of blood processing.

[0015] The invention also eliminates or at least substantially reduces the fouling reactions that have been known to be a major deterrent to the continuous use of an extracorporeal extraction device. In particular, as the primary transport surface in the membraneless exchange device (also referred to herein as a membraneless separator) of the invention is intrinsically non-fouling, a major deterrent to long-term or continuous operation is removed, opening the possibility to the design and construction of small, wearable devices or systems with the recognized benefits of nearly continuous blood treatment. Such a device or system could be very small and worn or carried by the patient (e.g., outside of a hospital or clinic setting), and could be supplied with external buffer reservoirs (in a back-pack, briefcase, or from a reservoir located in the home, located at the place of work, etc.). Further, because fouling would be reduced, and sustained operation at low blood flows over long times would be allowed, such anticoagulation as might be required is likely to have an effect confined to the extracorporeal circuit. As understood by those skilled in the art, avoiding systemic anticoagulation outside of the clinic is highly desirable.

[0016] The devices, systems and methods of the invention described herein also have the benefit of being capable of diffusing various blood components having different sizes. In particular, the flow of blood and a miscible fluid with which it is in contact can be controlled for the purpose of achieving the desired separation of components. For example, flow adjustment can minimize cellular migration across the interface. A sheath fluid can be used to give the discrimination of a membrane between large and small molecules that cannot be achieved by a denuded interface, no matter how exposure time (adjacent flows) is varied. For example, as explained below, various flow conditions may be used that cause blood cells to move away from the blood-liquid i

Problems solved by technology

The usefulness of blood processing techniques employing immiscible liquids is limited, however, because these immiscible liquids generally have very limited capacity to accept the blood components that it is desirable to extract.

Despite the benefits of therapies (e.g., hemodialysis) using the various forms of blood processing described above, the prolongation of life achieved is complicated by the progression and complexity of the disease the therapies are used to treat (few patients on dialysis are ever completely rehabilitated), and by several problems that are innate to the therapies themselves.

For example, problems arise with blood processing as a result of the contact of blood with extensive areas of artificial membrane (as in the case of hemodia

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