BioThrust™ ComfyCell: Bionic bioreactor for high-density & low stress cell culture

Designed with cell therapies in mind, BioThrust™ ComfyCell Incu is an all-in-one solution for scalable and controllable cell therapy manufacturing.

BioThrust’s ComfyCell bioreactors take a new approach to bioprocessing. Their advanced membrane aeration technology delivers 10× higher gas transfer than traditional systems, bringing major advantages for scaled and intensified cell and gene therapy (CGT) production, more reliable biologics processes, and more.

The gateway to ComfyCell system, ComfyCell Incu consists of a proprietary bionic bioreactor vessel package (BT-INT-C-ISU-0.3-1 for Single Cells/ Microcarriers, or BT-INT-C-ISU-0.3-2 for Spheroids/ Aggregates) with a compatible base controller unit with motor (BT-INT-NC-CTR-INCU).

BioThrust’s unique membrane stirrer technology

In traditional bioreactors, the impeller’s high rotation speed and bubble aeration generates high shear stress that damages or destroys sensitive cells. The foam produced during stirring and sparging can reduce the working volume inside the bioreactor, and necessitates the use of antifoam. This requires expensive purification to remove these agents. The low volume and low density of cultivated cells increases production cost.

BioThrust’ s patented membrane stirring system gently mixes and aerates your delicate and expensive cells in culture medium. The lower shear forces enable an increase of 400% in viable cell density. Foam is totally avoided, even in fermentation cultures, leading to 50% more working volume per reactor vessel. And 20-30% faster cell growth.

 BioThrust's proprietary membrane stirrer.

Conventional STRs (left) destroy cells through bubble aeration. The ComfyCell (right) gently mixes the media while providing cells with gases and nutrition needed.

BioThrust ComfyCell systems can cultivate 258 million cells per mL at a 2‑litre scale.

Benefits of BioThrust Bioreactor Systems

In ComfyCell bioreactors, Biothrust’s proprietary membrane stirrer enables aeration by diffusion through dense hollow-fiber membranes, without causing bubbling and foaming. This facilitates up to 10-fold higher gas transfer compared with conventional bioreactor systems. This leads to faster growth and higher cell viability.

The membrane is surface treated to prevent bio-fowling and blocking. So these high gas transfer rates are maintained throughout prolonged culturing. This leads to 400% more iPSCs compared with conventional bioreactors of similar sizes. O2 and CO2 levels can be continuously monitored and a controlled to prolong the life and heath of your cells and maintain homogenous cultivation conditions.

66bf028efa7300594ebf0cb8_Membrane 1-png

With gaseous diffusion happening through the BioThrust membrane stirrer itself and not through conventional bubbling and vigorous stirring by an impeller, agitation can be much slower and gentler. This results in much less shear stress on your delicate, expensive cells, and foaming is totally avoided.

ComfyCell bioreactors start small, with the smallest 300 mL models allowing 150 mL or 300 mL scale cultures. The single-use ComfyCell Incu system is ideal for R&D. The same single-use vessel is used as the base model in the ComfyCell Benchtop system, that is designed for process development. Larger benchtop models include 2 L and 10 L bioreactors. This larger size bioreactor is also suitable for the supply of cells for clinical studies.

The ComfyCell Incu does not have sensors built in; sample ports can be used to draw off samples for offline analytics. The ComfyCell Benchtop has several sensors (for DO, pH, Temperature and more) and a sophisticated controller unit for monitoring and controlling levels.

Note: the BioThrust proprietary membrane stirrer can be used to upgrade your existing glass bioreactor (2 L or 10 L).

BioThrust is also currently developing commercial-scale manufacturing systems, with up to 1000 L projected. (50 L and 200 L prototypes are available.)


Up to 10-fold higher gas transfer than other bioreactors

Linear scale-up from 300mL to 200L with one technology

Can leverage a wide range of perfusion systems or sensors

Incubator-based or closed system available

Understanding the ComfyCell Platform

ComfyCell Incu is the ideal small-scale place to start – it is the gateway to the whole ComfyCell platform. You can begin with ComfyCell Incu’s base unit and 300 mL bioreactors for your initial R&D, and then begin scaling up in with the same 300 mL bioreactor by swapping the Incu base unit for the Benchtop controller unit. Scale-up is made easy by the larger BioThrust membrane stirrers and bioreactor vessels having the same geometry as the ComfyCell Incu.

ComfyCell Benchtop systems are available as a complete Package from BioThrust. Alternatively, ComfyCell can be incorporated into your existing bioreactor infrastructure.

Comparing ComfyCell Systems

ComfyCell Incu

300 mL

ComfyCell-Incu-300mL-sq-1

Volume: Compatible with 300 mL ComfyCell Single-Use Vessel

Analytics: No inbuilt sensors, enables sampling and offline analytics

Environment: Requires placement in an incubator for process control

Perfusion: Up to three PG13.5 ports available for your needs

ComfyCell Benchtop

300 mL & up

ComfyCell-Benchtop-300mL

Volume: Seamless transition from 300mL to 10L with one controller

Analytics: Advanced online sensors for DO, pH, Temperature and more

Environment: Standalone closed system that fully controls cultivation process

Perfusion: Compatible with a wide range of perfusion processes

BioThrust ComfyCell. Next-generation bionic bioreactor for universal cell culture.

Examples

iPSCs

Human iPSC spheroids grown in E8 medium in the ComfyCell 300mL SUB at 70 rpm with consistent spheroid sizes. This run leverage BioThrust's in situ perfusion system to achieve almost 20 million cells per mL.

Fed Batch (ComfyCell Incu):
After 5 days, the ComfyCell Incu 300 mL with simple media change achieved >17-fold expansion and reached >2.5M cells/mL, starting from 150.000 cells/mL.

Perfusion (ComfyCell  Benchtop):
After 7 days, using BioThrust’s in situ perfusion, the ComfyCell Benchtop 300 mL reached almost 20M cells/mL with ~40-fold expansion, starting from 500.000 cells/mL.

Quality & Pluripotency:
During runs excellent viability is observed  (>90% at harvest) and pluripotency is fully maintained (99% of cells expressing TRA-1-60, SSEA-4 and Oct3/4 at harvest).

~40-fold expansion of cells grown in perfusion in ComfyCell Benchtop.

bm-MSC

Human bm-MSC (RoosterVial-hBM, RoosterBio) were expanded on micro-carriers (Synthemax II) in the ComfyCell Benchtop 300mL SUB and 2L Retro-Fit. MSC quality marker expression was excellent similar to 2D control (CD45: 0.02; CD105: 99.44; CD90: 99.88; CD73: 99.99)

Exosomes

Exosome secretion from human bm-MSC was excellent, outperforming 2D control ~5-fold and established competitor bioreactors ~2-fold. A yield of up to 6.4E9 particles per mL in the Benchtop 300mL SUB led to a total batch of >1.9E12 EVs despite MSC cell density of only 1.3E5 cells per mL

T-Cells

A mix of CD4+ & CD8+ cells from a healthy donor was successfully expanded (fed-batch) in the Benchtop 300mL SUB. With 60-fold expansion over 5 days, published STR results were outperformed 2-fold and 7.2E6 cells per mL were reached 2 days earlier (5 days instead of 7).

(i)NK

Highly sensitive iNK cells were expanded in the Benchtop 300mL SUB and 2L Retro-Fit with ease, reaching a solid 327-fold expansion (1000-fold from thaw) before being split. Important: Scaling from 100mL to 2L was done in under a week, confirming simple linear scale-up is possible.

BioThrust ComfyCell. Greater volumes of cells. Higher cell density. More viable cells grown closer to in vivo conditions in vitro. Lower production cost. Less risk for your sensitive, expensive cells.

BioThrust products currently available from REPROCELL

Description REPROCELL product catalog number BioThrust Product Code Pack Size
BioThrust™ ComfyCell Incu Base Unit & Motor
(100-240 VAC)		 BT-INT-NC-CTR-INCU int-nc-ctr-incu 1 unit
BioThrust™ ComfyCell Incu Single-Use Vessel 300mL
(Single Cells/Microcarriers)		 BT-INT-C-ISU-0.3-1 int-c-isu-0.3-1 1 unit
BioThrust™ ComfyCell Incu Single-Use Vessel 300mL
(Spheroids/Aggregates)		 BT-INT-C-ISU-0.3-2 int-c-isu-0.3-2 1 unit
BioThrust™ ComfyCell Incu 300mL Starter Package
(Single Cells/Carriers)		 BT-INT-PACK-INCU-0.3-1 int-pack-incu-0.3-1  1 pack
BioThrust™ ComfyCell Incu 300mL Starter Package
(Spheroids/Aggregates)		 BT-INT-PACK-INCU-0.3-2 int-pack-incu-0.3-12 1 pack

Notes:

  1. Starter packs contain base unit & motor plus 3 single-use vessels.
  2. Bioreactor vessels are not supplied sterile. Users must autoclave.
  3. Accessories included (pre-installed on each vessel): 3× PG13.5 port plugs, 2× silicone tubing & filters for gas connections, 4× c-flex tubing, Luer locks & clamps for sampling/ harvesting ports.

Speak to our experts about BioThrust ComfyCell