Factory-on-a-chip for production of biologically derived medicines/biopharmaceuticals/biologics/biotherapeutics

A method of preparing a therapeutic protein, the method comprising:

• synthesizing the therapeutic protein with a factory-on-a-chip microfluidic device comprising at least three separate units that can be stacked together to form a single unit, wherein the separate units comprise:
• (i) a microfluidic bioreactor unit equipped with a continuous collection channel for synthesizing a crude protein in a reaction within the microfluidic bioreactor unit, wherein the microfluidic bioreactor unit comprises cell extracts and a reaction mixture for cell-free expression of the crude protein, wherein a DNA or mRNA template is added to the cell extracts and the reaction mixture comprises biological extracts and/or reagents for expression of the crude protein;
• (ii) a microfluidic mixer/de-bubbler unit communicatively connected to the microfluidic bioreactor unit to dilute the crude protein and remove any air bubbles during mixing;
• and
• (iii) a microfluidic purification unit, communicatively connected to and downstream of the microfluidic mixer/de-bubbler unit, for capturing the crude protein and providing the purified therapeutic protein, wherein the microfluidic purification unit comprises:
• three polymethyl methacrylate (PMMA) layers comprising (a) a top layer, (b) a middle layer comprising at least one microcolumn, wherein each microcolumn has an inlet end and an outlet end, and (c) a base plate, wherein each microcolumn comprises chromatography resin, wherein the chromatography resin is retained in the microcolumn by a polytetrafluoroethylene (PTFE) frit positioned at the outlet end of the microcolumn, and
• wherein all fluid channels of the device are microfluidic.