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BioNOC™ II Cell Culture Macrocarriers

The Heart of Tide Motion Bioreactors

BioNOC II is a macroporous carrier that supports the growth of anchorage-dependent cells including animal, mammalian, and insect cells in either serum-containing or serum-free culture media.

It produces higher cell yields by providing a higher surface area (up to 2,400cm2/g) that allows the growth of up to 1x109 cells. Due to its high porosity (50-200 μm), adherent cells are easily exposed to the necessary amount of culture media and aeration. It is made of 100% pure polyester nonwoven fabric manufactured according to cGMP guidelines. With its structure, it has a high load-bearing capability to support packed-bed structure and a 45° angle that generates microscopic ready for mixing. The special geometric design and surface treatment on the carrier enhance fluid mixing, immobilization efficiency, protection from shear forces, and nutrient transfer during cell culture.

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BioNOC™ II Cell
BioNOC™ II Microcarriers
BioNOC™ II carriers are straight and uniform fibers that favor cell distribution and growth
Microscopic view: cell attached to BioNOC™ II
Illustration of how cells are situated within BioNOC™ II

Features

  • Productivity: Up to 2-3X109 cells/0.1 L of BioNOC II (for Vero cells)
  • Large growth surface area: Up to 2,400 cm2 /g of BioNOC II
  • High surface area to volume ratio: 160 cm2/ml
  • 100% Polyethylene Terephthalate (PET) material
  • 0.3 mm thickness for easy exposure to culture medium oxygen transfer
  • Non-pyrogenic, non-toxic, animal component-free
  • Special surface treatment to enhance biocompatibility
  • Special 3D geometric design to enhance mixing and support load-bearing capacity in packed-bed bioreactors
  • Compressible for higher cell density
  • Hydrophilicity stable for up to four years
  • Sterilizable by autoclave (if not pre-packed), gamma irradiation, and EO sterilization
  • Extremely low lint waste, convenient for adherent cell growth for protein or viral vaccine production

Applications

  • Growth of anchorage-dependent cells including animal, mammalian, and insect cells in packed-bed cell culture systems. Compatible with CelXrocker, CelCradle, TideXcell®, and other commercially available packed-bed culture equipment.
  • BioNOC II supports the growth of different cell lines, including CHO, CHO-K1, rCHO-hlgG, rC-127-TPA, HEK293, Hybridoma, Vero, Sf-9, Hi-5, BHK-21, rBHK Factor VIII, HepG2, Hela, Huh 7, RK-13, human foreskin fibroblasts, human muscle skeleton cells, human mesenchymal cells, and human embryonic stem cells.

Highlights

  1. 1. Mimics the cell’s in vivo environment

    Various anchorage-dependent cell lines such as Chinese Hamster Ovary (CHO), Kidney Epithelial Cell (VERO), Madin-Darby Canine Kidney Cell (MDCK), and Insect Cell (SF9) were used for vaccine, protein, and monoclonal antibody productions. The use of roller bottles and cell factories were prominent for the large-scale cell culture of these adherent cells; however, the development was costly, expensive, and always at risk of contamination.

    Microcarrier-based cell cultures have since made use of stirred tank bioreactors (STR) and fixed-bed bioreactors with macrocarriers. Compared with STR, the fixed-bed bioreactor has the capacity to protect cells from stressful conditions and perfusion culture model is easily achievable. Singapore-based macroporous carrier manufacturer Esco VacciXcell, supplies BioNOC™ II for use with different cell types. The use of macroporous carriers is a promising technique that has advantages in enhancing production capacity, improving the culture’s robustness, and facilitates process scale-up allowing the culture of various animal cells in high yield.

    Unlike other types of microcarrier for cell culture, a macroporous carrier such as BioNOC™ II creates a multilayer culture (3D cell growth) that allows cell to cell and cell to extracellular matrix interactions, mimicking the cell's in vivo environment. This is highly essential for multiple cellular processes, including differentiation and proliferation. Materials used in the creation of BioNOC™ II are FDA-approved, cGMP compliant, and this macroporous carrier manufacturing passed regulation guidelines USP Class VI, USP <87>, <83>, ISO 10993-5.

    Vero Cells: Vero Cells

    Live cells (fluorescent) staining of Vero cells on BioNOC II under 4x magnification. Calcein green staining of cytoplasm and Hoechst 33342 (blue) staining of the nucleus.

    Mesenchymal Stromal Cells: Mesenchymal Stromal Cells

    Black arrow points show ECM CL-MSCs cultured 4 days in BioNOC II - staining of collagen fibers with picro sirius red

  2. 2. Geometric design and surface treatment

    This macroporous carrier also has a distinct geometrical design that is specially folded to avoid overlapping of cells. This allows sufficient nutrient and oxygen transfer.

    Adherent cells attached to BioNOCTM II carriers are alternately exposed to aeration and nutrition phases by pumping media in and out of the packed bed.

    BioNOC II also exhibits great surface treatment. This macrocarrier can have a stable hydrophilicity for up to 4 years. It is non-cytotoxic that passed both serum and serum-free medium tests. Some cells are loosely adherent in nature, which is why they require with coating factors prior to cultivation to support higher attachment efficiency. However, not all microcarriers can support this. This limitation is being addressed with the use of BioNOC II. Due to its enhanced hydrophilicity, the addition of coating factors is easily accommodated.

  3. 3. Large Surface Area for Adherent Cell Growth

    BioNOC II presents straight and uniform fibers which are highly favored for cell distribution and growth. It also possesses higher density that prevents it from floating during the cell culture and remains stable all throughout the culture run.

    Vero cells have been cultured in BioNOC II and are grown to high densities from 2-3x109 using batch or perfusion mode of culture using Tide Motion bioreactors such as CelCradleTM and TideXcellTM. The surface area and the cell numbers achieved for Vero cell culture are shown to be very promising. These results prove that the BioNOC II macrocarrier allows for a robust linear scalability, and thus saves time, labor, and resources for process development.

    Day 6: Vero Cells Day 6
    Day 14: Vero Cells Day 14

    Figure 1. Live cell fluorescent staining of Vero cells on BioNOCTM II under 4x magnification. Calcein green staining of cytoplasm, Hoechst 33342 (blue) staining of the nucleus and Propidium Iodide stain for dead cells was done.

    The fold expansion of Vero cells from attachment on BioNOCTM II in a 1L packed bed to harvest using an automated TideXcell Harvesting System (TXLHS) was 19-fold and the efficiency of harvest was 93.6%.

    Ten (10) pieces of BioNOCTM II macrocarriers is equivalent to one (1) T-25 flask.

    bionoc
    Table 1. Cell growth in SFM of different carriers
    Model Cell Density
    Microcarriers 2.6 x 106 cells/ml
    Macrocarriers 5.8 x 106 cells/ml
    Table 2. Cell growth in serum-containing media of different carriers
    Model Cell Density
    Microcarriers 3.3 x 106 cells/ml
    Macrocarriers 6.5 x 106 cells/ml

    Comparisons

    BioNOC II Commercial Disks
    Material 100% PET PET / PP
    Dimension 55 mm x 10 mm strip Disk diameter 6 mm
    Specific Surface area 2,400 1,200
    Packed volume (ml/g) 15 10
    S/V 160 120
    Autoclavable OK OK
    Gamma irradiation OK
    Endotoxin tested (EU/ml) < 0.25 < 0.5
    Bioburden (CFU/gram) < 1 < 0.36
    Cytotoxicity tested Serum and serum-free culture test Yes
    Regulation guideline USP <87> <88>, ISO10993-5 USP <87> <88>, ISO10993-5
Frequently Asked Questions
25uL
BioNOC II matrix is made of 100% non-woven polyethylene terephthalate (PET). It is resistant to chemicals and autoclavable.
BioNOC II is applicable to anchorage-dependent cells, and we have widespread, successful experiences on the cell culture.
The shelf life is four years without decay of hydrophilicity.
There is approximately 2400 cm2 of effective surface area. There are 5.5 g of BioNOC II per 100 ml of bed volume.
  • CHO: CHO-S-SFM II (Gibco), CHO III A (Gibco), CHO-A-SFM (Gibco) , ExCELL 301 (JRH), HyQ PF-CHO (HyClone), HyQ-CCM 5 (HyClone), HyQ SFX-CHO (HyClone), IS-CHO-CD (IRVINE), proCHO4cdm
  • HEK-293: EX-CELL 293 (JRH), Pro293a-CDM (CAMBREX), HyQ SFM4 HEK293 (HyClone)
  • HEK-293: EX-CELL 293 (JRH), Pro293a-CDM (CAMBREX), HyQ SFM4 HEK293 (HyClone)
  • VERO: VP-SFM (Gibco), Plus VERO (VACCIXCELL), ICN-VERO (ICN), PEEK-1 (Biochrom)
  • Sf-9: SF-900 II (Gibco), EX-CELL 420 (JRH), EX-CELL 400
The essence of a low bioburden in BioNOC II is that it does not encourage the growth of microorganism on the surface of the carriers, which may be a source of contamination. BioNOC II also has low lint content making it ideal for 3D cell culture.
Phase-contrast inverted microscope with a good depth of field function is recommended.

  • Testing BioNOC™ II Carriers