Figure 1.
Set-up of the filtration unit employed in the experiments.
The bulk was fed using a Tandem 1082 Pump and the retentate recirculated to the feed tank. the pressure was monitored by in-line transducers at the inlet, retentate outlet, and permeate outlet. was kept constant at 1–1.2 bar by a flow restriction valve. TRIS saline buffer at pH 8 was used as diafiltration buffer.
Table 1.
Membrane characteristics and feed flow rates used.
Figure 2.
(average
SEM) for the different UF membranes.
(A) R&D prototype devices with different materials, namely RC, xRC, and PES. (C) The pilot production devices were only made of xRC and compared against commercially available GE HF 750 kDa (PES UF 7) modules. (B, D) water flux (LMH) at various values of ranging between 0.5 and 2 bar.
Figure 3.
Flux recoveries (average SEM) after usage and after CIP with 1 M NaOH for (A) different R&D prototypes and (B) pilot production devices.
In both cases the highly cross-linked regenerate cellulose (xRC) was able to achieve higher flux recovery after usage than the PES-based membranes. After CIP, all membranes recovered their initial flux except for the PES HF 3 and 5 modules and RC type C membrane.
Figure 4.
Total virus particle recovery as a function (average SEM) of the concentration diafiltration volume for (A) different R&D prototypes (B) pilot production devices.
The plots display the same process first operating in concentration mode and then diafiltration. In both cases the highly cross-linked regenerate cellulose xRC showed the highest recovery yield when compared to PES menbranes.
Table 2.
Recovery of infectious particles (IP) and processing time for 10-fold concentration for the different pilot production and R&D UF devices.
Figure 5.
HCP clearance (average SEM) as a function of the concentration/diafiltration volume for different R&D prototypes (Fig.A) and for the pilot production devices (Fig.B).
Both figure display the HCP clearance value after 10 fold concentration. The HCP clearance does not show important differences among the different cassettes and or HF. A slight increase in clearance is observed for the PES based cassettes and for the GE HF 750 kDa (PES HF 7). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article)
Figure 6.
DNA clearance as a function (average SEM) of the concentration/diafiltration volume for different R&D prototypes (Fig.A) and for the pilot production devices (Fig.B).
The plots display the same process first operating in concentration mode and then diafiltration. At both R&D and pilot production scales, the PES-based membranes lead to an increased DNA removal compared to their RC and xRC counterparts. (For interpretation of references to color in this caption, the reader is referred to the web version of the article).
Figure 7.
Flux decay curves as a function of the filtration time Fig.(A and (B). Throughput (liter of feed processed in the unit of time (h), given a defined membrane area (m2)) Fig. C and D.
The value reported in Fig. C and D are after to 10-fold concentration and 2 diafiltration volume. For the large cut off R&D membranes a strong flux decay is observed at the beginning of the filtration(Fig A). Pilot production devices and GE HF 750 (PES HF 7) show the same decay profile (Fig.B). Cassettes with RC Type B and xRC Type E show the highest throughput (Fig. C), the throughput for the GE HF 750 is 2 fold less compared to the pilot production cassette membranes (Fig.D). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article)
Figure 8.
Sieving curve for visualization of different pore size by using different molecular weight dextrans, ranking between 10 and 10
g/mol.
RC and xRC exhibit a narrower rejection range than the other membranes and, therefore, a more homogeneous pore size distribution. Two commercially available RC cassette are compared against showing tighter pore sizes even for the membrane rated as 1000 kDa. GE HF 750 kDa (PES HF 7) exhibits the largest cut-off and wider pore size distribution. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article) PES based cassettes and HF both outperform the xRC and RC based cassettes.
Figure 9.
Trade-off between throughput, indicated as liter of feed processed in the unit of time (h), given a defined membrane area (m2), and infective particle recovery yield.
The values referrer at 10 times concentration factor. The orange area on the right top corner depicts the best membranes. RC and xRC membranes showed the highest throughput coupled with high recovery yield. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article)
Figure 10.
SEM pictures of PES membrane, xRC Type F membrane and HF 7.
A, B and C indicate the cross section structure for the flat sheet membrane and hollow fiber, while D, E and F illustrate the surface structure.
Table 3.
Characterization of xRC, RC and PES ultrafiltration devices.