Bioreactor and Extraction Heat Exchangers

Jacket loops held to a tenth of a degree, media sterilized and cooled, solvent chilled to -40 F and recovered.

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From a warm jacket to a cold solvent

Bioprocessing and botanical extraction sit at opposite temperatures and use the same sanitary exchanger families. A mammalian cell bioreactor is held at 37 C and a microbial fermenter at 30 to 37 C, in both cases within a tenth of a degree, by a temperature control unit that circulates water through the vessel jacket and through a small exchanger that adds plant steam heat or chilled water cooling on demand. Media is sterilized at 121 C for 15 to 30 minutes in batch or continuously through a heater, hold and cooler, and harvest and buffers are chilled to 2 to 8 C for downstream steps.

Extraction plants for CBD, hemp and other botanicals chill ethanol to -40 F (-40 C) before it meets the biomass so that waxes and chlorophyll stay behind, recover the ethanol by evaporation and condensation, and winterize the crude by chilling it in ethanol to drop the remaining lipids. Hydrocarbon plants condense propane and butane after the extraction vessel. The exchangers are sanitary plate or tube-in-tube on propylene glycol or a low-temperature fluid, with condensers on the solvent vapor.

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Sanitary bioreactor temperature control unit with a compact double tubesheet exchanger and jacket loop pump beside a stainless vessel

Turndown from 300 kW to 3 kW is the TCU design problem

A 20,000 liter microbial fermenter can throw several hundred kilowatts; the cooler is sized on that peak at the warmest chilled water with 30 percent margin. At the cold end, glycol at -45°F is about 60 cP, so ethanol chillers are sized on the glycol side.

Temperature control unit skid with steam and chilled water injection exchanger

Bioreactor TCU and media exchangers

  • Jacket water held at setpoint within 0.1 C, 20 to 200 gpm loop
  • Steam-to-water heater and chilled water cooler, or one dual-purpose unit
  • Turndown from full cooling at peak metabolic load to trim heating
  • Media sterilizer: 121 C hold then cooling to inoculation temperature
  • 316L, 20 Ra, double tubesheet where WFI-based media is the product
Sanitary plate ethanol chiller and vertical solvent condenser on an extraction skid

Extraction chillers and condensers

  • Ethanol from ambient to -40 F on glycol or low-temperature fluid
  • Plate or tube-in-tube rated for the -40 F fluid viscosity
  • Solvent recovery condenser sized on evaporator vapor rate
  • Winterization chiller for crude in ethanol at -20 to -40 F
  • 316L product side, hazardous-area electricals on the skid

Recommended construction by bioprocess and extraction duty

Bioreactor exchangers are small and precise; extraction exchangers are cold and sized on solvent rate. Both are chosen by the fluid and the separation needed.

DUTY / CONDITION RECOMMENDED CONSTRUCTION WHY
Bioreactor TCU heater and cooler on jacket water U-Tube Compact steam-to-water and chilled-water-to-water sets with free expansion through daily cycling; no product contact so single tubesheet is acceptable
Continuous media sterilizer, 121 C heater, hold and cooler Double Tubesheet WFI-based media against plant steam and cooling water; the gap protects the batch
Harvest, buffer and product chilling to 2 to 8 C Double-Wall Plate Small volumes, tight approach on chilled glycol, leak visibility between plates; opens for inspection
Ethanol chilling to -40 F for extraction Gasketed Plate Highest coefficient on a thin solvent; gaskets rated for ethanol and -40 F; low holdup of cold solvent
Crude oil in ethanol winterization, viscous at -20 to -40 F Single Tube-in-Tube Large bore for a fluid that thickens as it chills; lipids that drop out do not plug a plate channel
Ethanol or hydrocarbon vapor recovery after evaporation Vapor Condenser Sanitary shell-and-tube condenser sized on evaporator vapor rate; sub-cooled return to the solvent tank
Bioreactor TCU
U-Tube
Media sterilizer
Double Tubesheet
Ethanol chilling
Gasketed Plate
Winterization
Single Tube-in-Tube

Designing TCU, sterilizer and extraction exchangers

A bioreactor temperature control unit is a small closed water loop with a pump, a heater and a cooler. The heater is a steam-to-water exchanger, often a U-tube or a plate, that adds heat during start-up and trims during the run; the cooler removes the metabolic heat of a dense culture, which on a 2,000 liter mammalian reactor is a few kilowatts and on a 20,000 liter microbial fermenter can be several hundred. The exchangers are sized on the peak cooling load at the warmest chilled water with a 30 percent margin, and the heater on the start-up time from ambient. Turndown is the design problem: the same cooler that removes 300 kW at peak must remove 3 kW at the end of the run without cycling the jacket temperature, which is done with a small approach, a well-sized control valve and a loop volume that damps the swings.

Continuous media sterilization heats media to 121 C, holds it for a validated time in a sloped hold tube and cools it to inoculation temperature, and it is the process that decides whether the batch is contaminated. The heater is double tubesheet because the media is made on WFI and the utility is plant steam; the cooler is double tubesheet for the same reason on tower water; regeneration is media-against-media through a third double tubesheet unit where the plant wants the steam savings. Media with dissolved sugars and salts fouls the heater over a campaign, and the run length is set by area margin the way a dairy UHT heater's is.

Ethanol chilling to -40 F is a viscosity and gasket problem. Ethanol at -40 F is about 4 cP, glycol at -45 F is about 60 cP, and the coefficient on the glycol side collapses; the exchanger is sized on the glycol side, the glycol flow is generous, and a low-temperature fluid replaces propylene glycol where the chiller can supply it. The plate gaskets are chosen for ethanol at that temperature, and the frame is insulated and vapor-sealed so the plates do not ice from room air. The holdup of a plate pack is small, which matters when a cold solvent is also a flammable one.

Solvent recovery is a condenser sized on the evaporator's vapor rate at the chilled water or glycol available. Ethanol at 173 F atmospheric boiling condenses on tower water; under vacuum at 100 to 120 F it needs chilled water, and the condensate is sub-cooled before it returns to the tank so the vent does not carry ethanol. Hydrocarbon recovery condenses propane and butane at pressure on chilled glycol, and the exchanger, the skid and the electricals are specified for a classified area.

A tenth of a degree at 37 C, forty below at the other end

Cleanability and separation in bioprocess

Anything that touches media, harvest or product is 316L electropolished to 15 to 20 Ra, drainable and CIP and SIP compatible. TCU exchangers on jacket water are utility equipment and do not need that finish, which is why a plant can put a plain U-tube on the jacket loop and save the pharmaceutical specification for the sterilizer and the buffer cooler. HeatX quotes both grades on one order.

Single-use and pilot scale

Single-use bioreactors move the temperature control to the jacket of the bag holder, and the TCU exchanger is the same small water-loop heater and cooler. Pilot and clinical suites often want one skid that serves several vessels; that is a larger TCU with a distribution header, sized on the coincident peak.

Winterization and decarboxylation

Winterization dissolves crude extract in ethanol and chills it to -20 to -40 F for 24 to 48 hours so that fats and waxes precipitate before filtration. The chiller is a tube-in-tube or wide-gap plate because the solution thickens and drops solids as it cools. Decarboxylation heats the extract to 220 to 250 F for an hour; that is a jacketed vessel with a hot oil or steam set behind it, and the fume condenser is a small vapor condenser on tower water.

What to send

For bioreactors: vessel size, peak cooling load or organism and cell density, setpoint and tolerance, chilled water and steam available. For extraction: solvent, flow, inlet and outlet temperatures, chiller fluid and temperature, evaporator vapor rate for condensers, and the area classification. Call and talk it through with an engineer: 1-805-484-2992

Common FAQs

The jacket water never touches product, so the TCU heater and cooler are utility exchangers in 304 or 316 with ordinary connections. The media sterilizer and any product cooler are the sanitary, double tubesheet units.

Propylene glycol at 60 percent reaches -40 F but is viscous there; potassium formate or a silicone-based low-temperature fluid gives better coefficients. HeatX sizes the exchanger on whichever the chiller supplies.

Yes, with gaskets specified for ethanol and the temperature, an insulated frame and generous glycol flow. Plates are the usual choice for the ethanol chiller; tube-in-tube takes over for the winterization step where solids drop out.

On the evaporator's vapor rate at operating pressure, the cooling fluid available and the sub-cooling needed to keep the vent clean. Give HeatX the evaporator rating and the chilled water or glycol temperature.

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