A modular scale-down reactor

The scale-down reactor according to anyone of the preceding claims, wherein the disk comprises at least 1 aperture, such as at least 2 apertures, such as at least 3 apertures, such as at least 4 apertures, such as at least 5 apertures, such as at least 6, such as at least 7 apertures, such as at least 8 apertures, such as at least 9 apertures, such as at least 10 apertures, such as at least 11, such as at least 12 apertures, such as at least 13 apertures, such as at least 14 apertures, such as at least 15 apertures, such as at least 16, such as at least 17 apertures, such as at least 18 apertures, such as at least 19 apertures, such as at least 20 apertures, such as at least 25, such as at least 30 apertures, such as at least 35 apertures, such as at least 40 apertures, such as at least 45 apertures, such as at least 50 apertures, such as at least 60 apertures, such as at least 70 apertures, such as at least 80 apertures, such as at least 90 apertures, such as at least 100 apertures, such as at least 200 apertures, such as at least 300 apertures, such as at least 400 apertures, such as at least 500 apertures, such as at least 600 apertures, such as at least 700 apertures, such as at least 800 apertures, such as at least 900 apertures, such as at least 1000 apertures, such as at least 1100 apertures, such as at least 1200 apertures, such as at least 1300 apertures, such as at least 1400 apertures, such as at least 1500 apertures,

• optionally wherein the apertures are circular and further wherein said apertures are between 0.5 mm and 100 mm in diameter, such as between 50 mm and 100 mm in diameter, such as between 0.5 mm and 50 mm in diameter, such as between 0.5 mm and 40 mm in diameter, such as between 0.5 mm and 30 mm in diameter, such as between 0.5 mm and 20 mm in diameter, such as between 0.5 mm and 10 mm in diameter, such as between 0.5 mm and 5 mm in diameter, such as between 0.5 mm and 4 mm in diameter, such as between 0.5 mm and 3 mm in diameter, such as between 0.5 mm and 2 mm in diameter, such as between 0.5 mm and 1 mm in diameter, such as between 1 mm and 2 mm in diameter, such as between 2 mm and 100 mm in diameter, such as between 2 mm and 50 mm in diameter, such as between 2 mm and 40 mm in diameter, such as between 2 mm and 30 mm in diameter, such as between 2 mm and 20 mm in diameter, such as between 2 mm and 10 mm in diameter, further optionally wherein the size, shape and number of apertures is selected to provide a specific exchange area between the sub-volumes of adjacent reactor units,
• further optionally wherein the size, shape, number and location of the apertures, and/or the impeller, is selected to provide a specific flow profile between the sub-volumes of adjacent reactor units,
• even further optionally wherein the specific exchange area and/or the specific flow profile between the sub-volumes of adjacent reactor units are designed to provide a specific mixing time in each sub-volume of each adjacent reactor unit, preferably wherein said mixing time is different in each sub-volume of adjacent reactor units and wherein the mixing time of a sub-volume of a reactor unit is defined as the time required for achieving a pre-determined degree of homogeneity in said sub-volume of said reactor unit,
• finally optionally wherein the mixing time of a sub-volume of a reactor unit is dependent on the volumetric power input.

A method of simulating, modelling, monitoring or modifying the conditions of a reactor comprising a liquid composition in a bioreactor or live fermentation process, comprising the steps of:

• a. providing the scale-down reactor according to any one of the preceding claims;
• b. defining the total reactor volume by reversibly adding a number of inner reactor units (3);
• c. defining the number, position and design of the at least one disk (7);
• and
• d. optionally, defining the design of the mixing shaft (5) and one or more impeller (6);
• wherein the conditions to be simulated, modelled, monitored or modified are selected from the group consisting of:
• reaction volume, temperature, pH, gas concentration, metabolite concentration, cellular mass, cellular density, enzymatic kinetics, absorbance, and mixing time, and
• wherein the reactor is at least 300 L,
• optionally wherein one or more of the conditions is simulated, modelled, monitored or modified in each sub-volume of the scale-down reactor, further optionally wherein one or more operating conditions in the scale-down reactor are equal or similar to said corresponding operating conditions in the reactor, wherein said operating conditions are selected from:
• e. Power input value (P/V);
• f. aspect ratio;
• g. impeller tip speed;
• h. mixing time;
• i. volumetric mass transfer coefficient;
• and/or
• j. oxygen transfer rate;
• wherein P is the Power Input and V is the Volume in the reactor, and wherein P may be calculated according to the formula:
• P
• =
• Po
• ⋆
• ρ
• ⋆
• N
• ⋆
• D
• 3
• wherein V is the volume of the reaction liquid, Po is the Power number for the impeller, p is the fluid density, N is the rotational speed of the impeller and D is the impeller diameter;
• wherein the aspect ratio is defined as the inner diameter divided by the inner height of the reactor;
• wherein the impeller tip speed may be calculated according to the formula:
• Impeller tip speed=π*D*n
• wherein D is the impeller diameter and n is the impeller rotation speed;
• wherein the mixing time is defined as the time required for achieving a pre-determined degree of homogeneity in the reactor;
• wherein the volumetric mass transfer coefficient (kLa) and/or the oxygen transfer rate (OTR) may be calculated according to the formula:
• k
• L
• ⁢
• a
• =
• OTR
• /
• (
• C
• L
• ⋆
• -
• C
• L
• )
• wherein C*L is the dissolved oxygen concentration at air saturation and CL is the dissolved oxygen concentration in the liquid phase;
• optionally wherein the scale-down reactor is operated in the same mode as the reactor, such as in batch, fed-batch or continuous mode, and further wherein the scale-down reactor is of the same type as the reactor, wherein the type is selected from a stirred tank reactor and a bubble column reactor.

A method of manufacturing a scale-down reactor, said method comprising:

• a. providing
• i. a reaction compartment comprising at least two reactor units, wherein said at least two reactor units are reversibly attached to one another via connection means,
• wherein the at least two reactor units comprise a top unit (1) and a bottom unit (2), and optionally comprise one or more further inner reactor units (3);
• wherein said reactor units when attached to one another form a fluid-tight reaction compartment for receiving a reaction liquid therein;
• wherein one or more of said units comprise one or more inlet fluid apertures (4) and one or more outlet fluid apertures (4),
• ii. optionally, a mixing shaft (5) placed vertically in the reaction compartment, said mixing shaft comprising one or more impellers (6), and
• iii. at least one disk (7) inserted horizontally between two adjacent reactor units or horizontally within an inner reaction unit, said disk comprising at least one aperture (16) allowing the fluid contained in the adjacent reactor units to pass through it, optionally said disk comprising at least one shaft aperture (8) allowing the mixing shaft to pass through it;
• b. assembling said reaction units, disk and optionally said mixing shaft.

A method of controlling a scale-down reactor, said method comprising:

• a. providing
• i. a reaction compartment comprising at least two reactor units, wherein said at least two reactor units are reversibly attached to one another via connection means,
• wherein the at least two reactor units comprise a top unit (1) and a bottom unit (2), and optionally comprise one or more further inner reactor units (3);
• wherein said reactor units when attached to one another form a fluid-tight reaction compartment for receiving a reaction liquid therein;
• wherein one or more of said units comprise one or more inlet fluid apertures (4) and one or more outlet fluid apertures (4),
• ii. optionally, a mixing shaft (5) placed vertically in the reaction compartment, said mixing shaft comprising one or more impellers (6), and
• iii. at least one disk (7) inserted horizontally between two adjacent reactor units or horizontally within an inner reaction unit, said disk comprising at least one aperture (16) allowing the fluid contained in the adjacent reactor units to pass through it, optionally said disk comprising at least one shaft aperture (8) allowing the mixing shaft to pass through it;
• iv. at least one probe located in at least one of the reactor units, configured to measure at least one property of the reactor, such as pH, dissolved oxygen, temperature, real-time flow cytometry and/or concentration of one or more products present inside the reactor,
• b. assembling said reactions units, disk and optionally said mixing shaft,
• c. providing a computing unit containing a digital representation of the scale-down reactor,
• d. receiving data from the at least one probe, and
• e. varying operating conditions of the scale-down reactor until a simulated optimal state provided by the digital representation of the scale-down reactor is achieved.