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BioCradle™

CELLULOSE MACROPOROUS MICROCARRIER
FOR EFFECTIVE CELL CULTURE

About BioCradle

Microcarrier cell culture is extensively used in the commercial production of vaccines and biopharmaceuticals based on adherent cells. BioCradle microcarriers are composed of macroporous cellulose beads with positively charged N, N-diethylaminoethyl (DEAE) groups. The large specific surface area, superior cell adherence, and cell proliferation characteristics offered by BioCradle facilitate high-density cell culture. Inside the BioCradle pores, cells are protected from the shear forces generated within the stirred culture vessel making this technology ideal for the scale up of adherent cell culture. The positive charge also enables floating cells to be efficiently immobilized and cultured at high density. Furthermore, the high-density culture conditions within the microcarriers influence cell-to-cell interactions and promote cellular functions such as protein synthesis. These unique features enable the BioCradle microcarriers to function as ‘cradles’ for the culture cells.

Cross-linked Cellulose

Charges throughout matrix

Rotation image of BioCradle

Cross Section image of BioCradle

Advantages

  1. 01Expand
    Cell Culture Period
  2. 02Efficient Cell Culture
    (High Density Culture)
  3. 03Non Toxic Matrix
  4. 04Suitable for AutoClave Sterilization

Porous

  • High Surface Area
  • Protections for Cell (Cradle)

Cellulose

  • Stable, Safe

Optimized Particle Size & Density

  • Uniform Cell Growth
  • good suspension

From Surface Culture to Interior Culture

BioCradle was developed to efficiently culture adherent cells in a stirred culture vessel. It is particularly suited to the production of biopharmaceuticals using recombinant cells such as CHO cells. Its positively charged macroporous structure also makes it useful for immobilized culture of floating cells such as hybridomas.
Cells were found in the interior of the BioCradle beads, where the effects of shear stress are lessened.

Cross section SEM image of an empty bead
Cross section SEM image of bead from 30days culture of CHO-K1 cells

Influence of Shear Stress on Cell Growth

Inside the BioCradle pores, cells are protected from the shear stress generated in the stirred culture vessel, making this technology ideal for the scale up of adherent cell culture.
Cell number was higher for culture with BioCradle beads over a broader range of higher ISF (Integrated Shear Factor) values.

ISF = (2πNDi)/(Dt - Di)
Di: the diameter of the impellor
Dt: the diameter of the culture flask
N: the rotation speed of the impellor

Comparison of Microcarriers

Comparison study was conducted by using vero cell ATCC CCl-81 as are presentative of vaccine manufacturing cell line. Below table is a list of microcarriers we evaluated. We evaluate 2 types of BioCradle, one is low charged, the other is high charged. Additionally we evaluated two types of commercially available surface type microcarrier. As the below table shows, BioCradle has larger surface area.

Microcarrier Type Surface Modification Particle Size (um) Specific Surface Area
(cm2/g-dry weight)
BioCradle L DEAE, low charge 200 - 280 11,000
BioCradle H DEAE, high charge 200 - 280 11,000
product A* DEAE 147 - 248 4,400
product B* collagen 141 - 211 2,700

*commercially available(surface type)

As a result of vero cell growth, high charged BioCradle showed highest cell density when microcarriers concentration was same.

Figure 1.
The results of vero cell growth on the different types of microcarriers with serum containing medium.

Methods

Stirred cell culture
  • Vessel: 125 mL spinner flask (WHEATON)
  • Medium Volume: 70 mL (10% FBS supplemented)
  • Medium exchange: once/day [from 3 days to the end],exchange rate = 100%
  • Initial cell concentration: 2 x 105 cells/mL
  • Agitation: 50 rpm
  • Incubator: 37 ℃, 5% CO2
  • Microcarrier: 2 g/L-medium

Topics

News
BioCradle website was opened.
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Specification

We are willing to provide free sample of each type (5g).

Characteristics BioCradle H BioCradle L
Base material Cellulose
Particle size 200 – 280 μm
Charge group Diethylaminoethyl (DEAE)
Quantity 20 g, 1000 g
Ion Exchange capacity 1.65 – 1.95mmol Cl-/g 0.90 – 1.20mmol Cl-/g
Specific gravity 1.03g/mL
Effective surface area 1.1m2/g dry
Average pore diameter 30μm
Swelling factor 43 – 55 ml/g 42 – 46 ml/g
Product Name Catalog No. Quantity
BioCradle H20 BCRH0020 20g
BioCradle H1000 BCRH1000 1000g
BioCradle L20 BCRL0020 20g
BioCradle L1000 BCRL1000 1000g

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BioCradle™ is a trademark of Asahi Kasei Corporation.