Hyper-productive chromatography system and process
A hyper-productive chromatography technique includes providing a scalable and stackable chromatographic cassette, loading a sample to be processed, operating the scalable chromatographic cassette having an adsorptive chromatographic bed having a volume greater than 0.5 liter by establishing a flow at a linear velocity greater than 500 cm/hr with a residence time of the loading step of less than one minute.
1. A method of performing a Hyper-Productive chromatography process comprising:
providing a stackable chromatographic cassette;
loading a sample to be processed;
operating the stackable chromatographic cassette having an adsorptive chromatographic bed having a volume greater than 0.5 liter by establishing a flow at a linear velocity greater than 500 cm/hr;
and
wherein a residence time of the loading step is less than one minute.
2. The method of claim 1 wherein the adsorptive chromatographic bed comprises one of:
a polymeric media;
a hydrogel media;
a compressible adsorptive media; and
a semi-compressible adsorptive media.
3. The method of claim 2 wherein the polymeric media is polymethylmethacrylate (PMMA).
4. The method of claim 1 wherein the linear velocity is greater than 1000 cm/hr.
5. The method of claim 1 wherein the residence time in the loading step is less than 0.5 minute.
6. The method of claim 1 wherein the residence time in the loading step is less than 0.25 minute.
7. A method of performing a Hyper-Productive chromatography process comprising:
providing at least one chromatographic cassette having an adsorptive chromatographic bed having a bed volume greater than one liter and comprising one of:
compressible chromatographic adsorptive media;
semi-compressible chromatographic adsorptive media;
soft chromatographic adsorptive media;
placing the at least one chromatographic cassette in a cassette holder;
loading a sample to be processed;
operating the chromatographic adsorptive bed establishing a flow at a velocity greater than 1000 cm/hr; and
wherein a residence time in the loading step is less than one minute.
8. The method of claim 7 wherein the residence time in the loading step is less than 0.5 minutes.
9. The method of claim 7 wherein the residence time in the loading step is less than 0.25 minutes.
10. The method of claim 7 wherein soft chromatographic media comprises one of:
polymethylmethacrylate (PMMA);
agarose Protein-A media;
cation exchange media;
anion exchange media;
mixed-mode media;
size-exclusion chromatography (“SEC”) media;
controlled-pore glass (“CPG”) media.
11. The method of claim 7 further comprising operating the chromatographic cassette having a linear pressure drop over a velocity range of zero cm/hr to about 1200 cm/hr.
12. The method of claim 7 , further comprising operating at a total cycle productivity of greater than about 60 g/L/hr (GLH), with media having a average bead size less than about 50 μm at velocities greater than about 500 cm/hr.
13. The method of claim 7 , further comprising operating at a total cycle productivity of greater than 100 g/L/hr (GLH) with media having a average bead size less than about 40 μm at velocities greater than about 800 cm/hr.
14. The method of claim 7 , further comprising operating at a total cycle productivity of greater than 150 g/L/hr (GLH) with media having a average bead size less than about 30 μm at velocities greater than about 1000 cm/hr.
15. The method of claim 7 , wherein the adsorptive chromatographic bed comprises chromatographic beads having an average bead size less than 30 μm.
16. The method of claim 7 further comprising stacking a plurality of chromatographic cassettes within the cassette holder to form a chromatographic adsorptive bed having a scaled up bed volume larger than about five liters.
17. The method of claim 7 further comprising operating at a constant hydraulic resistance independent of velocity.
18. A system for performing a Hyper-Productive chromatography process comprising:
a scalable chromatographic cassette holder;
wherein the stackable chromatographic cassette is disposed in the scalable chromatographic cassette holder; wherein the stackable chromatographic cassette is capable of being operated according to claim 1 .
19. The system of claim 18 , wherein the stackable chromatographic cassette comprises an fused deposition modeling (FDM) 3-D printed lattice having porous printed surfaces sealed with a sealant.
20. The system of claim 19 , wherein the sealant is one of:
epoxy;
polyurethane;
silicone; and
UV-curable adhesive.
21. The system of claim 19 further comprising a chamber enclosing the lattice; and
wherein the sealant is applied to one of:
an outside surface of the chamber enclosing the lattice; and
an inside surface of the chamber enclosing the lattice, where the sealant impregnates wetted surfaces of the chamber and excess sealant is withdrawn before the excess sealant cures.