Systems and methods for closed loop, real-time modifications of patient cells

A subject-connected, closed-loop system for the modification of a cell, the system comprising:

• a) an inlet conduit adapted for parenteral communication with the subject and adapted for receiving blood from the subject;
• b) a cell separation module in fluid communication with the inlet conduit, the cell separation module comprising a cell separator configured to produce a fraction enriched in a target nucleated blood cell type using the blood from the subject, and the cell separation module further comprising a first sampling unit for obtaining a sample of the fraction;
• c) a cell customization module in fluid communication with the cell separation module so as to receive the nucleated blood cell fraction enriched in the target cell type from the cell separation module, the cell customization module configured to present one or more modifying agents to the target nucleated blood cells, thereby generating modified cells, and the cell customization module further comprising a second sampling unit for obtaining a sample of the modified cells, wherein the cell customization module is configured to deliver one or more nucleic acids encoding a chimeric antigen receptor (CAR) to the target nucleated blood cells, thereby generating CAR T cells;
• and wherein the system is further configured to permit cell separation, delivery of a nucleic acid encoding a CAR to a target cell type to generate CAR T cells, and return of CAR T cells to the subject in real time in a closed loop;
• d) a detector configured to conduct a detection operation and operably interfaced with the cell separation module, the cell customization module, operably interfaced between the cell separation module and the cell customization module, and/or operably Interfaced between the cell customization module or the cell separation module and the subject;
• e) an outlet conduit adapted for parenteral communication with the subject and for conducting modified target cells parenterally to the subject;
• and
• f) a processor configured to control an operation of the inlet conduit, the cell separation module, the cell customization module, the detector, or the outlet conduit or the system;
• wherein the inlet conduit, the cell separation module, the cell customization module, the detector, and the outlet conduit of the system are connected in a fluid-sealed closed-loop adapted for parenteral connection with a patient at both ends of the fluid sealed closed-loop, and the system is configured to permit cell separation, delivery of a modifying anent to the target nucleated blood cell type and delivery of the modified cells to the subject in real time within the fluid sealed closed-loop.