Abstract: A method is disclosed for producing specially prepared bacteria of the genus Clostridium for producing solvents, enzymes, antibiotics, toxic proteins, or spores. Cell elongation to a critical length of at least about 3x is induced in an economical, abundantly available growth medium by serial subculturing under controlled conditions to effect synchronization of growth in the number of the cells and their effective mass and to produce a substantially homogeneous cell population. At least about 0.01M of a divalent cation such as calcium is added to the synchronized cells of critical length to stabilize the cells against death, lysis or aggregation. Where bacterial production of solvents is desired, cell division is inhibited by temperature shift or by chemical means when the cells reach a synchronized solventogenic state. Solvents produced by the specially prepared bacteria may be economically and readily recovered by conventional distillation procedures or the like.

Abstract: A fermentation apparatus for the production of alcohol provides for continuous circulation of must through the apparatus. A pumping column is connected to a top of a fermentation vat via a back pressure valve and extends above the vat for pumping fermented must transferred from the vat via the back pressure valve. A must degassing device is connected to the pumping column at a position above the column. A must return pipe is connected to the degassing device and to a bottom portion of the vat for conveying must in a turbulent flow to the vat and to a hydraulic stirring device positioned in the bottom portion of the vat for stirring must in the vat. A gas injection device is connected to an upper portion of the return pipe for introducing gas into the flow of must in the pipe. Alcohol may be collected by a decanter connected to the return pipe and/or by a device for heating the must in the pumping column.

Abstract: By culturing cells in an apparatus containing a first zone in which a cell suspended medium is present and a second zone in which liquid containing a physiological saline solution and/or nutrient sources is present, the first zone being separated from the second zone by a septum with characteristics, such as pores size or electrostatic charges, which impedes the cells from freely permeating through, while allowing at least one of nutrient sources, cell wastes or the product to move between the first zone and the second zone via the septum to proliferate cells in the first zone, wherein a flow rate via the septum is controlled in such a manner that the cell count moved from the first zone into the second zone via the septum does not exceed the cell count increased by cell growth in the first zone. Thus, cell culture at a high cell density can be achieved in a large scale.

Abstract: An apparatus is disclosed for the controlled production of microorganisms by photosynthesis in a closed photobioreactor. The closed photobioreactor contain a photosynthetic culture in a substantially sealed environment and provides a system for recirculating the reactant gas through the culture. This closed loop system can be operated with expensive carbon isotopes (i.e., .sup.13 CO.sub.2 or .sup.14 CO.sub.2). Also, a system is provided for removing the molecular oxygen produced in the photosynthesis reaction from the closed photobioreactor. Furthermore, a pH-regulated control valve is utilized for controlling the addition of reactant gas to the culture in response to the alkalization of the culture.

Abstract: A post-fermentation degassing technique is provided for use in degassing foamed fermentation broths containing cultured microorganisms. Such a broth is charged while pressurized through a nozzle to form a spray suspension in a gaseous spray chamber located in a gravitationally upper part of a degassing vessel. The spray chamber is vented to the atmosphere. The spray suspension is coalesced to form a bulk liquid phase located in a gravitationally lower portion of the degassing vessel whereby the upper surface of such bulk liquid phase forms the bottom surface of such spray chamber. The nozzle is so oriented that the spray suspension it produces is downwardly directed towards the surface of the bulk liquid phase and the layer of foam characteristically foamed thereon. Additionally, a portion of the bulk liquid phase is recycled to the upper part of the vessel through a second nozzle to form a second spray suspension which is coalesced into the bulk liquid phase.

Abstract: A multi-stage reactor-separator for the fermentative production of volatile inhibitory products from non-volatile substrate includes a stirred tank reactor and a packed or tray-type gas-liquid contacting column separator. Each reactor and separator form a stage and a plurality of stages may be stacked into a tower, or otherwise placed to operate consecutively, forming a reactor-separator in which stages having gas flowing cocurrent to the liquid flow in the separator portion form an enriching section, and stages having gas flowing countercurrent to the liquid flow in the separator portion form a stripping section. In a method of using the reactor-separator, a volatile fermentation product is produced and simultaneously separated into a gas phase.

Abstract: A bioreactor includes three compartments. A middle compartment is meant to contain a biocatalyst and is separated from opposite end compartments by semipermeable membrane. The middle compartment is in the form of a vertically extending cylinder with domed top and bottom walls. The opposite end compartments are also in the form of domes but extend horizontally. Lower supply and upper discharge lines are connected to each of the end compartments. An agitator is connected in the bottom of the middle compartment and a degasser is connected to the top of the middle compartment.

Abstract: A process for starting up the continuous production of butyric acid by fermentation of a medium containing a starting amount of a nutrient substrate and a microorganism that converts the nutrient into butyric acid, that avoids an excess of nutrient in the fermentation broth and comprises the steps of (1) fermenting in a fermentor in batch style an amount of the medium that is substantially less than the working volume of the fermentor until the amount of the nutrient not yet converted is no more than a small fraction of the starting amount, (2) adding medium to the fermentor without removing any of the fermentation broth, until it contains approximately its working volume, then, (3) while continuing the addition, removing the fermentation broth containing the butyric acid product at a continuous rate that maintains a constant volume of medium in the fermentor, and thereafter maintaining continuous operation of the fermentation.

Abstract: A method is provided for controlling production of low molecular weight heparin (LMW-heparin) when depolymerizing heparin with heparinase in a reaction mixture in a reactor. Depolymerization to a desired average molecular weight is monitored by measuring an increase in UV-absorption (preferably at 230-235). When the absorption has reached a value for a desired molecular weight, the depolymerization is stopped or LMW-heparin having the desired molecular weight is continuously removed from the reaction mixture. In a preferred embodiment, the reaction mixture is subjected to ultrafiltration to produce a filtrate containing LMW-heparin, and a retentate which is recycled to the reactor. UV-absorption and refractive index of the filtrate are measured, and depolymerization is controlled in accordance with the measured absorption and refractive index to produce a filtrate containing a LMW-heparin of low polydispersity and predetermined molecular weight.

Abstract: There is disclosed an apparatus, a device, and a method using the inventive device and apparatus for the sequential enrichment of a particular microorganism to a threshold level to allow for its detection. The use of the apparatus for sequential microbial enrichment shortens the time period normally spent to enrich samples to permit the growth of enough microorganisms to detect the particular microorganism(s) of interest. The invention eliminates the need for multiple manual transfers of potentially biohazardous materials.

Abstract: A flow-through cell cultivation apparatus and method is described. The flow-through cell cultivation system comprises a flowcell, a chamber inside the flowcell for holding cells, and a flowcell holder. The flowcell has a lower intake port for flowing liquid nutrient through a cellbed inside the flowcell and an upper outlet port for flowing the liquid nutrient out of the flowcell. The flowcell also includes a chuck for receipt of a thermal probe. The probe is made of electromagnetically non-interactive material. The flowcell is enclosed inside the flowcell holder. The flowcell holder includes a pair of intake ports into a cavity having an open end at the flowcell for turbulently flowing a temperature controlled gas against the flowcell. The cavity has rough walls to promote the turbulent flow. The flowcell holder includes an exhaust port for flowing the gas out of the flowcell holder which also serves as a port for another thermal probe.

Abstract: To improve the yield and/or reduce the energy cost in carrying out a microbiological or enzymatic process in a reactor and to make the reaction conditions essentially independent of the size of the reactor, it is proposed on make use, as a reactor, of an endless circulation tube in which the reaction components are circulated essentially according to a plug flow and in this process are fed through one or more in-line mixers fitted inside the tube. This method and reactor are suitable in particular for the preparation by fermentation of polysaccharides, especially xanthan, in which water, a production medium containing one or more sugars and nutrient salts and an inoculating material of a suitable aerobic bacterium are introduced into the the reactor tube and exposed to fermentation with air being supplied.

Abstract: A methanol synthesis and an ethanol synthesis are integrated into a single continuous process with the by-product carbon dioxide generated in the ethanol synthesis being utilized in the methanol synthesis. The methanol synthesis and ethanol synthesis can be further integrated with isobutylene synthesis with by-product hydrogen formed during isobutylene synthesis being used as a raw material in the methanol synthesis. In the preferred embodiments the ethanol synthesis utilizes Zymomonas mobilis bacteria in anaerobic fermentation in order to maximize the amount of carbon dioxide produced in a form which can be utilized in the methanol synthesis, to reduce carbon dioxide emissions and to provide an ethnaol product which is highly suitable for reaction with the isobutylene to form ethyl tertiary butyl ether.

Abstract: This bioreactor comprises two enclosures (60,62) connected by first and second porous carbon tube (66,68) for the circulation of the nutrient medium (19) and immersed in the culture medium (9), internal mineral, microporous membranes (70) located in each first and second tube for ensuring the passage of the nutrient medium to the culture mdium and whilst serving as a barrier for contaminants, external, mineral, microporous membranes (72) located outside each first and second tube for ensuring the passage of the nutrient medium to the culture medium and while serving as barrier for the cells and the proteins contained in the culture medium, at least one porous mineral tube (86) for the extraction of the substances produced by the cells, which is isolated from the two enclosures and equipped with an external, microporous, mineral membrane impermeable to the cells, but permeable to the macromolecules produced in the culture medium.

Abstract: A process including multistage continuous fermentation followed by batch fermentation with carefully chosen temperatures for each fermentation step, combined with an asporogenic strain of C. acetobutylicum and a high carbohydrate substrate concentration yields extraordinarily high butanol and total solvents concentrations.

Abstract: Peptide preparation is carried out by a continuous process by supplying a serine protease or peptidase enzyme retained in a reaction vessel with an alkyl ester of an N-protected amino acid or oligopeptide and a recycle stream containing an amino acid or oligopeptide to form an N-protected chain extended peptide, separating the N-protected chain extended peptide by adsorption on a hydrophobic absorbent, and eluting and recovering the adsorbed N-protected chain extended peptide. Adsorption is carried out without adjusting the pH from that in the reaction vessel, and adsorber effluent is recycled to the recycle stream. The protease or peptidase enzyme may be immobilized, and there is substantial exclusion of organic solubilizers in the reaction vessel. A preferred N-protecting group is an N-phenacyl group. The N-protecting group can be separated from the N-protected chain extended peptide with a deprotecting enzyme to recover the chain extended peptide.

Abstract: A temperature monitoring method and apparatus for monitoring the temperature within a mass of organic matter moved through a composting vessel. An elongated, stationary probe extends through the vessel from one end toward another end thereof. A plurality of temperature measuring devices are mounted along the probe. The probe may extend through a compaction ram and be provided with a sleeve for accommodating movement of the ram relative to the probe. A decoupling device provides for decoupling of the probe from a mounting base and an extraction device permits the probe to be extracted from the vessel for replacement thereof. The probe provides a method of monitoring temperature in the mass and a method of composting by monitoring temperature in the mass and regulating the temperature of the mass in response thereto.

Abstract: The invention relates to nucleotide sequences, including a substantially purified gene which codes for an oxygen-binding protein, and a gene promoter/regulator which is useful in subjecting the translation/transcription of DNA sequences to selective regulation by external control, and plasmid vectors containing those nucleotide sequences, which are valuable bioprocessing catalysts for enhancing the growth characteristics of cells, and increasing production of various proteins and metabolites of those cells. Methods for the use of these nucleotide sequences and related plasmids for a range of applications including oxygen supply to cells, growth enhancement, expression of various gene products, enhancement of oxygen-requiring processes, binding and separation of oxygen from liquids and gases, and a range of oxidative reactions are also disclosed.

Abstract: A compartmentalized horizontally mounted rotatable cylindrical digester drum is provided with inter-compartment transfer buckets each having an inlet opening substantially congruent to a segment of the circular partition separating one compartment from the next. In addition one or more annular flanges are located in each treatment compartment extending radially inwardly from the cylindrical wall of the drum. The transfer buckets may be rectangular prismatic in contour with a bottom wall within the confines of the drum coincident with the chordal boundary of the segment and an upper wall spaced radially outwardly of the cylindrical wall of the drum.

Abstract: An apparatus for submerged culture of tissue cells in which gas is supplied to the culture medium in an upright sterilizable container through a rotating hollow shaft having a plurality of sets of radially extending blades from which the gas is discharged only along upper surfaces of the blades within a cage formed by vertically spaced hollow baffle plates connected by hollow posts through which gas is supplied to the baffle plates and is charged into the nutrient medium through porous parts of the plates.

Abstract: Fuel grade ethanol is produced in continuous process employing fermentation, solvent extraction of the ethanol, extractive distillation of the ethanol-solvent extract to provide water fraction and vacuum stripping for separation of the fuel-grade ethanol and regenerated solvent.The solvent is recycled. An isoparaffin is used as a solvent and this solvent can be modified with a long chain fatty acid, alcohol or fatty alcohol or long-chain esters. Alternatively, many modifiers may be used neat.

Abstract: Plant cells are cultivated in vitro without agitation or fixation, e.g. for the production of a metabolite or a biotransformation. The liquid medium may be circulated for removal of the desired products.

Abstract: A spin filter for removing substantially cell-free medium from a stirred suspension culture vessel, wherein a stationary baffle is arranged in the interior space of the spin filter to disrupt liquid flow therein and minimize the tendency of cells to collect on and foul the inner-facing filter surfaces, the filter surface being sized to substantially exclude materials greater than about 8 to 10 microns, and the spin filter being rotatable independent of, and in a rotational direction opposite to, the vessel stirring device.

Abstract: A water-soluble substrate and an oily substrate are continuously reacted with immobilized lipase in a reaction vessel having vertically maintained apart upper and lower conically-shaped regions, respectively, for separation of a water-soluble product and an oily product, a plurality of lipase reaction zones each containing immobilized lipase capable of being fluidized and an agitating means, and a plurality of intermediate separation zones for separation of an oily substance and a water-soluble substance. The lipase reaction zones and the intermediate separation zones are disposed alternately between the upper and lower conically-shaped separation regions. Boundaries between the lipase reaction zones and intermediate separation zones are pervious to liquid but impervious to the immobilized lipase.

Abstract: The present invention provides a membrane method for the enzymatic synthesis of peptides accomplished by shifting the chemical equilibrium that exists in a reaction mixture between charged or ionized reacting amino acids and uncharged or non-ionized peptide product in the presence of a proteolytic enzyme such as thermolysin. The equilibrium is shifted by diffusion of the unchanged peptide product across an ion-rejection membrane which removes the uncharged peptide from the reaction mixture and preferably the diffused uncharged peptide is quickly converted to a charged species that cannot back-diffuse into the reaction mixture so that the uncharged peptide is effectively "pulled" across the membrane. An enzymatic conversion of the uncharged species utilizing an esterase having proteolytic activity such as aminoacylase I is disclosed. Copermeating reactants can be separated from the product mixture and returned to the reaction mixture.

Abstract: Process for carrying out a sparged reaction, including providing one or a plurality of vertically-disposed reaction tubes, introducing a sparging gas under pressure into the bottom of the tube, separating and withdrawing the sparging gas from the top of the tube and passing the separated sparging gas in indirect heat exchange with at least part of the outside surface of the tube. The process is particularly suitable for carrying out an exothermic reaction, such as a fermentation reaction for the production of single cell protein, in which the bottom of a plurality of reaction tubes are disposed in a water bath, the withdrawn sparging gas is sprayed across the tops of the tubes, preferably after reducing the pressure to cool the same, and water is withdrawn from the bath and passed downwardly along the outside of the tubes.

Abstract: A process for producing a physiologically active substance by a combined enzymatic method is disclosed.

Abstract: The cell culturing system of the present invention includes a tubular membrane, e.g. hollow fiber, cartridge. Provision is made for the continuous circulation of a nutrient-containing medium through the tube side of the cartridge by pumping the nutrient-containing medium in an endless loop. The cells to be cultured are placed within the cartridge on the shell side where the desired extracellular products are accumulated. Nutrients are assimilated into the cell culture through the semipermeable tubular membranes and waste products are removed by passing through the semipermeable membranes into the recirculating nutrient-containing medium. Within the endless loop are located a circulating pump, an oxygenator and a pH probe. The system additionally includes a variable delivery feed pump for continuously injecting fresh nutrient-containing solution into the loop, which feed pump is operated at a rate responsive to the measured pH.

Abstract: Process and apparatus is disclosed for removing pollutants from a waste gas stream comprising culturing in a rotary biocontactor a biomass capable of assimilating the pollutants and producing harmless metabolites. The waste gas stream is brought into contact with the biomass within the biocontactor. The biocontactor includes a plurality of discs mounted for rotation within the biocontactor. The waste gas stream in passing over the exposed biomass on the disc results in the pollutants being absorbed by the biomass. In turn the biomass assimilates the pollutants and produces harmless metabolites. The gas stream with a substantial percentage of pollutants removed therefrom and containing any gaseous metabolites is exhausted from the biocontactor.

Abstract: Microorganisms or animal cells are cultured in a fluidized or fixed bed bioreactor on porous inorganic sintered support spheres containing inwardly continuous and outwardly open pores. The spheres have a density and diameter such that shear forces created under fluidized bed conditions shear off microorganisms or animal cells grown out of the pores and on the surface of the spheres. Culturing may be carried out in a fixed bed continuous reactor and the bed subjected to intermittent fluidized bed conditions to shear microorganisms or animal cells off the sphere surfaces. The spheres may be coated with a thin plastic layer to increase resistance to abrasion. Also, the spheres may be provided with a surface layer of inorganic and/or organic material for improving immobilization of microorganisms or animal cells.

Abstract: A process for producing ethanol in the substantial absence of fusel oils by Zymomonas fermentation wherein fermentation is carried out under conditions unfavorable for the growth and replication of yeast. In the preferred embodiment, Zymomonas are initially inoculated into a carbohydrate containing medium undergoing active fermentation by yeast, then the fermentation conditions altered to inhibit growth and replication of yeast.

Abstract: A process for the treatment of corn steepwater. The steepwater is incubated for a sufficient time to develop biomass before corn steepwater is fed continuously to the developed biomass at a rate such that the residence time of the steepwater in contact with the biomass is in excess of 4 hours.

Abstract: A continuous fermentation process is performed in an apparatus system having at least two circulation fermenters arranged in a cascade. Fresh must is introduced into a first fermenter for fermentation with a flocculating yeast, growth of the yeast in the first fermenter being promoted by introduction of oxygen. The fermenting must and yeast are transferred from the first fermenter to a second fermenter and then to any subsequent fermenters of the cascade serially. In the second and any subsequent fermenters, the growth of yeast is inhibited. After passing through the last fermenter of the cascade, be it the second or a subsequent fermenter, yeast is separated from fermented must, and the separated yeast is removed from the system and is not recycled.

Abstract: A fluidized bed reactor and reaction process, particularly well-suited for culturing cells, for example, for tissue culture and fermentation processes, are described which involve the treatment of at least a portion of the fluid exiting the fluidized bed reactor in a side loop in a manner to alter its temperature or composition, e.g., oxygenation, with recirculation of this treated fluid to the reactor as a portion of the fluid causing bed fluidization.

Abstract: This invention provides a continuous bioconversion process in which a non-growth toluene substrate is bio-oxidized by a specific microbe mutant strain to accumulated extracellular muconic acid at a bioreactor production rate of at least about 5 grams of muconic acid per liter of fermentation medium per hour.Essential features of the invention process include a continuous feed of whole cell-containing fermentation broth from an auxiliary cell growth and enzyme induction fermentation zone into the main fermentation zone, and a purge stream of whole cell-containing fermentation broth from the main fermentation zone.

Abstract: A cylindrical hollow carrier for microorganisms is prepared by subjecting a nonwoven fabric having a specific gravity of not greater than 1.0 to a surface smoothing treatment at an elevated temperature of 200.degree. to 450.degree. C., then pressing with a roller to give the nonwoven fabric a thickness of 1 to 5 mm and a weight per unit area of 30 to 300 mg/cm.sup.2 and then forming the nonwoven fabrics into a cylindrical hollow shape. The carrier has a compression weight of not less than 400 g, and preferably an outer diameter of about 25 to 100 mm and a length of about 40 to 60 mm. The nonwoven fabric may be formed of 35 to 90% fibers of 50 to 600 denier and 10 to 65% fibers of 20 to 1 denier.

Abstract: A process to produce products, in particular polysaccharides, from filamentous fungi, in an immobilized cell bioreactor wherein the fungus is fixed and adheres to the surface of a porous, non-particulate support and aqueous liquid medium is passed through the immobilized system and product containing medium is recycled or withdrawn from the system.

Abstract: In the production of ethanol by continuous fermentation in a fermentor (4) with continuous stillage recirculation (19, 20) to the fermentor, the fermentation liquid (6) continuously withdrawn from the fermentor is first sieved in a straining step (7) for separation of coarse solid particles. Then the fermentation liquid (11) is separated in a yeast separation step (12), from which a yeast stream (13) is recirculated to the fermentor (4) and a yeast-free stream (14) is fed to a primary distillation step (9). From the bottom stream (16) from the distillation step (9) a part (19, 20) is recirculated to the fermentor and another part is subjected to final stripping in a secondary distillation step (10).

Abstract: Biological reactions are carried out with a unitary structure, preferably formed of a ceramic material, having a plurality of flow passages including first and second sets of flow passages arranged so that individual passages of the first set are adjacent individual passages of the second set and are separated by walls formed of the ceramic material. The ceramic material is porous to provide mass transfer of gaseous oxygen and biological reaction products while containing liquid in the second set of passages. Walls of the passages may be covered with a gaseous oxygen permeable membrane. Inside walls of the second set of passages may coated with a compound adapted to immobilize biological reaction materials.

Abstract: A continuous microorganism cultivating apparatus has a stock solution tank which receives a stock solution for a microbial reaction and is provided with a cylindrical filter through which the stock solution is passed. The stock solution is separated by the filter into filtrate containing a metabolic product and concentrated liquid containing microbes. The concentrated liquid is then recycled to the stock solution. The filter is a ceramic filter having a multitude of pores, which is connected to a back wash device.

Abstract: Bioprocessing apparatus and method using centrifugal acceleration of cells to maintain a culture within a reaction zone. The reactor has an inflow at a relatively distance inlet and an outflow at an inwardly spaced point toward the rotational axis. The reaction chamber has an inwardly diverging zone with a velocity gradient which captures cells of varying sizes. A recycle system is preferably used to recycle medium containing nutrients for the culture microbes. Byproducts of the cells are removed by the circulated medium and can be extracted using a desired extraction process.

Abstract: To improve the yield and/or reduce the energy cost in carrying out a microbiological or enzymatic process in a reactor and to make the reaction conditions essentially independent of the size of the reactor, it is proposed to make use, as a reactor, of an endless circulation tube in which the reaction components are circulated essentially according to a plug flow and in this process are fed through one or more in-line mixers fitted inside the tube. This method and reactor are suitable in particular for the preparation by fermentation of polysaccharides, especially xanthan, in which water, a production medium containing one or more sugars and nutrient salts and an inoculating material of a suitable aerobic bacterium are introduced into the said reactor tube and exposed to fermentation with air being supplied.

Abstract: Biocatalyst particles of a predetermined size are retained in a liquid mixture by oscillating in a vertical direction a screen having openings with a passage width greater than the size of the biocatalyst particles. Preferably the screen is substantially cylindrical having an interior that encloses a liquid column in a container which may be substantially cylindrical. Gas may be introduced into the liquid column and mixing means can be used to create flow currents on either or both sides of the screen. The mixing means may be a plurality of perforated discs connecting the screen to a centric gas delivery pipe in the column. Oscillating of the screen may be at a frequency between 10 and 100 Hertz and an amplitude between 0.5 to 50 times the biocatalyst particle size. Changing the frequency and amplitude varies retaining action of the screen.

Abstract: Exoenzymes, such as proteases, xylanases and amylases, are obtained continuously by cultivation of exoenzyme-producing microorganisms in one step in a fermenter which is operated with continuous flow and in which a deficiency state corresponding to maximal enzyme productivity is effected. Optical density of the culture (as a measure of the biomass density) and exoenzyme concentration in culture can be monitored to control the timing and extent of the deficiency state. It is particularly advantageous to impose an oxygen limitation and to maintain the deficiency state continuously by exerting an effect on the oxygen input.

Abstract: A process is disclosed for the production of substantially pure fructose from sucrose-containing substrates. The process comprises converting the sucrose to levan and glucose, purifying the levan by membrane technology, hydrolyzing the levan to form fructose monomers, and recovering the fructose.

Abstract: A method is provided for producing a product by enzyme-catalyzed reaction using supercritical fluid as a solvent. Improved reaction times, conversion efficiencies and/or other efficiencies (such as improved ease of product recovery) are obtained.

Abstract: A process is disclosed for continuously producing erythritol by cultivating erythritol-producing microorganisms under aerobic conditions. The process comprises the steps of: maintaining the concentration of dissolved oxygen in a culture broth in a fermentation tank at not less than 0.2 ppm; separating a part of the culture broth into a concentrated liquid in which the concentration of cells is increased and a clarified liquid by a cell separator; returning the concentrated liquid to the fermentation tank; controlling an amount of the clarified liquid to be extracted outside an erythritol-producing system and an amount of the culture broth and/or the concentrated liquid to be extracted outside the producing system such that the concentration of the cells in the culture broth in the fermentation tank may be kept in a range from 40 to 200 g/l when calculated as a weight of dried cells; and recovering erythritol from the clarified liquid.

Abstract: A system for continuous production and removal of a biological substance from a dispersed cell culture. The system comprises a reactor adapted to maintain the cell culture under incubating conditions and means for pumping limited volumes of the culture fluid from the reactor and through an external substance separation device adapted to extract the substance in a limited time on a continuous basis without collection of, or damage to, the dispersed cells. Less than 5% of the total culture fluid volume is outside the reactor (Volume outside or Vo) at any time and a given dispersed cell is outside the protective environment of the reactor for less than about two minutes, as expressed by the following relationship, ##EQU1## In preferred embodiments the external device comprises a plurality of substance-extracting, porous, hollow fibers through which the culture fluid, substance, and dispersed cells are continuously passed.

Abstract: A process for preparing optically active indoline-2-carboxylic acid by an optical resolution, which comprises subjecting a racemic ester of (R,S)-indoline-2-carboxylic acid having the general formula [(R,S)-I] to the action of an enzyme or a microorganism having a stereo-selective esterase activity, which is capable of asymmetrically hydrolyzing the racemic ester [(R,S)-I] to give optically active indoline-2-carboxylic acid having the formula [II*] so as to produce the hydrolysis product, i.e. optically active indoline-2-carboxylic acid [II*] and an unreacted optically active ester of indoline-2-carboxylic acid having the general formula [I*], isolating each optically active form, and further, if necessary, hydrolyzing the obtained optically active ester [I*] to give an optical antipode of the acid [II*].According to the process of the present invention, optically active indoline-2-carboxylic acid with a high optical purity can be prepared in a simple process with a good yield.

Abstract: An improved bioreactor system for culturing cell products is disclosed in which novel system components are employed to reduce cost and increase reliability. The system includes a simple in-line heater for heating the nutrient fluid, thereby obviating the need for an expensive incubator. Gas bubbles formed during the heating of the nutrient fluid are removed by a novel gas trap that requires no operator intervention. A humidifier humidifies an aerating gas before it is passed through an oxygenator, thereby preventing water within the nutrient fluid from evaporating, with a consequent increase in nutrient fluid concentration. The operation of the humidifier is efficiently combined with that of a nutrient fluid heat exchanger so that a pump is not required to circulate the heat exchanger water bath. The system further includes a valve and pump arrangement whereby fresh nutrient fluid can periodically be introduced and spent nutrient fluid periodically drained without operator intervention.