Glossary

Explanation of the terms, words and phrases we all use

 

A

Aerobic – growing in the presence of Oxygen.

Affinity – attraction between particles or substances.

Adherent – micro-organism with affinity to anchor, adhered onto a surface, such as immobilised cells or stem cells or micro-organisms in general adhering to a surface.

Algea – are a very large and diverse group of simple in water living eukaryotic organisms.

Anaerobic – Growing in the absence of air or Oxygen.

Angstroem - the unit of length equal to 10−10 m (one ten-billionth of a metre). Named after Anders Jonas Angstroem (1814–1874).

Antibody – An range of infection-fighting proteins in the blood that tags, neutralizes and helps deactivate foreign micro-organisms or toxins. Different antibodies are secreted by different B-cells (B-lymphocytes) from the disease-fighting immune system in the mammalian body. See Polyclonal Antibodies and Monoclonal Antibodies.

Anti foam – a chemical fluid (such as surfactant Pluronic F68) added to the media during cultivation for reduced foaming and associated problems with damaging micro-organisms and blocked sterile filters, etc.

ASC – Adult Stem Cells - undifferentiated cells, found in tissues or organs of the body after embryonic development, that are capable of self-renewal and differentiate into specialized cells to replenish dying cells and regenerate damaged tissues.

ATF – Alternating-Tangential-Flow – a method of perfusion operation for continues cultivation under non-steady-state conditions. Sequentially the broth is taken from the bioreactor and alternating passing the semi-permeable membrane. The ATF method characterized by its inherent ability to reduce filter deposits. The membrane insure high cell densities are kept inside the bioreactor and allow the product to pass the membrane. Technology and concept developed by RefineTech now from Repligen. See also PTF.

AODPD - Air-Operated-Diaphragm-Positive-Displacement Single-Use-Pump's available from www.pumpcell.com

Aseptic – Sterile, free from bacteria and viruses.

Assay – A testing technique for measuring a biological response or for determining characteristics such as composition, purity, activity and weight.

Atropos - a compact Drive Unit for the Euterpe Air-Operated-Diaphragm-Positive-Displacement (AODPD) Single-Use-Pump cell's available from www.pumpcell.com.

Autoclaving - Autoclaves use pressurized steam to destroy microorganisms, and are the most dependable systems available for the decontamination of laboratory waste and the sterilization of laboratory glassware, media, and reagents. Somewhat facility and resource demanding.

Autologous cell therapy - A therapy using cells derived from a patient’s own body. This often involves the extraction of cells and an ‘ex vivo’ (outside the body) step of growing and multiplying them before transplanting them back into the patient. Also know as Personalised Medicine.

B

Bacteria – robust micro-organism with strong cell wall, fast growing with often 20 minute doubling time, high oxygen demand, product are often intracellular, limited in ability to produce molecules larger than 50 kDa, can not produce fully humanized antibodies.

Batch - a bioreactor operation method to which no fresh media is added and no used media and/or cultured liquid removed, typically lasting less than one week.

BactoVessel – a Single-Use-Fermenter and conventional Stirred-Tank-Reactor replacement product designed specifically for fermentation of bacteria, yeast, fungus, etc. Available from www.cercell.com

Bag – a flexible (most often single-use) container made from thin plastic foil serving various purposes, media preparation and storage, bioreactor container, product storage, size range from 250 ml to 2 m3.

Beta rays – same as and look also at E-beam irradiation - difference of Beta and Gamma

BioBLU – a polystyrene based Single-Use-Bioreactor ranging in size from 0.3 to 50 litre for batch or fed-batch cultivation of various cell lines in suspension manufactured by Eppendorf

Biologics, biologics product, biotherapeutics  and biologic material – a wide range of medicinal and therapeutic products and drugs such as: antibiotic, antibodies, recombinant antibodies, monoclonal antibodies, vaccines, proteins, recombinant proteins, proteins molecules, blood components, allergenics, somatic (adult) stem cells, tissues created by biological processes – typically considered to be large molecules and often opposite of chemical industrial produced materials such as powder based pills

Bio-mass – biological products derived from living or recently living micro organisms.

Bio-mass-sensor – a sensor for measuring biomass based on the capacitance characteristics of large micro-organisms or by measuring small micro-organisms, particles also known as Optical Density (OD), opacity available from Hamilton Company.

Bioreactor – means a physical device, a container, a bag, a vessel which support biologically active environment suitable for cultivation of micro-organism such as mammalian cell lines, performing a desired process where the micro-organism are populated inside the bioreactor compartment.

BHK – Baby Hamster Kidney cells, adherent cell line, typically grown in media with high content of serum. The cells were derived in 1961 by I. A. Macpherson and M. G. P. Stoker.

Broth – the liquid content in a fermenter or bioreactor; cells, micro-organisms, nutrients, waste, liquid, etc.

Buffer – a solution containing a weak acid and a conjugate base of this acid.

C

Cavities – holes or small holes often in teeth, here originating from cave meaning a volume ranging from meter in size down to micro meter in size open in at least one end.

Cavitation - is the formation of vapour cavities in a liquid, cavitation usually occurs when a liquid is subjected to rapid changes of pressure that cause the formation of cavities where the pressure is relatively low. When subjected to higher pressure, the voids implode and can generate an intense shock wave.

CerCore - or known as CellCore - a patented Perfusion-Single-Use-Bioreactor (P-SUB) scaffold concept available from company PerfuseCell able to efficiently express a product from suspension cell, adherent cells or continiously proliferate stem cells at high cell density.

Cell retention – such as in a perfusion bioreactor integrating a hollow fibre Cross-Flow-Filter (CFF) with a pore size significant smaller than the cells being processed. Flushing the broth the CFF allow media, harvest removal and cell retention.

CellVessel – a customizable Single-Use-Bioreactor designed for batch or fed-batch cultivation of various cell lines in suspension manufactured by www.cercell.com

CellMembra - a Perfusion-Single-Use-Bioreactor (P-SUB) designed for high density cell retention via the integrated Clio Single-Use-Pump and Cross-Flow-Filter device operation in Pulsating-Tangential-Flow (PTF) mode. Available from www.perfusecell.com

CellReady – a non-customizable polycarbonate Single-Use-Bioreactor in one size of 3 litre Vessel Volume for cultivation of various cell lines in suspension manufactured by Millipore.

CellTank – a Perfusion-Single-Use-Bioreactor (P-SUB) product used for cultivation of various cell lines under steady state conditions. Incorporates CerCore and is available from www.perfusecell.com

Centrifuge – an apparatus which exposes a suspension for high G-forces in order to separate precipitant and supernatant of different density.

CerPhragm - a patented Single-Use-Pump (SUP) concept available from company PumpCell able to replace both the peristaltic and centrifugal pump.

CFF - Cross-Flow-Filter module such as a hollow fiber filter module of a number of parallel arranged extruded straw arranged inside a transparent plastic tube. Highly relevant for a perfusion setup combined with a pump and a bioreactor as in ATF and PTF setup - suppliers are SpectrumLabs, WaterSep, GE, Parker, etc

CFR 21 part 11 - concerns “Electronic Records and Electronic Signatures” as edited by the USA FDA.

CFR 21 part 58 - concerns GLP - Good Laboratory Practices as edited by the USA FDA.

Chemical industrial produced materials - such as powder based small molecules pills typically the opposite of biological produced large molecules.

Chemostat – perfusion batch - a bioreactor to which fresh medium is continuously added, while culture liquid is continuously removed to keep the culture volume constant.

CHO – Chinese Hamster Ovary cells originate from work performed in 1957 by Theodore Puck in the US. Since 1987 the CHO is widely used in biotechnology and medical research and expression of biologicals. Today, CHO cells are the most commonly used mammalian hosts for industrial cultivation for expression of extracellular recombinant protein therapeutics. The hamsters have only 22 chromosomes and the CHO cells typically a size of 15-18 µm. The genome is fully described at www.chogenome.org

Chromatography - a method for purification or capture involving a device that holds chromatographic active materials, typically one or more steps is needed in a purification process for protein capture and/or separations. 

CIP – Cleaning-in-Place.

Clio - a Single-Use-Pump concept available from company PumpCell able to replace the peristaltic pump and further used in the CellMembra product available from company PerfuseCell.

Clothothe Drive Unit for CellMembra Perfusion-Single-Use-Bioreactor as available from www.perfusecell.com.

CMO – Contract Manufacturing Organization.

Code of Federal Regulations - CFR - are regulated and edited by the USA Food and Drug Administration (FDA).

Collagen - is a group of naturally occurring proteins found in mammals such as skin, tendon, vascular ligature, organs, bone, cell membrane, hair, placenta.

Compartment - defines a liquid filled housing in a liquid filled bioreactor vessel in which micro-organisms are hosted and cultivated.

Conductivity - is a measure of how well a solution conducts electricity. To carry a current a solution must contain charged particles, or ions. Most conductivity measurements are made in aqueous solutions, and the ions responsible for the conductivity come from electrolytes dissolved in the water. Salts (like sodium chloride and magnesium sulfate), acids (like hydrochloric acid and acetic acid), and bases (like sodium hydroxide and ammonia) are all electrolytes. Although water itself is not an electrolyte, it does have a very small conductivity, implying that at least some ions are present. The ions are hydrogen and hydroxide, and they originate from the dissociation of molecular water.

Confluence – adherent mammalian cells proliferate and cover the entire surface available.

Continuous cultivation - steady state conditions with constant exchange of media, fresh media against used media, and harvest from the reactor. Micro-organisms may be harbored static in a packed bed allowing a constant media flow.

Cross-Flow-Filter - see CFF and Hollow-Fiber-Membrane 

Cultivation - hosting of micro organism in a bioreactor compartment for production purposes, such as expression of a molecule or proliferation performed typically by mammalian cell lines or insect cell lines.

D

Dalton – the unit of molecular mass, very nearly equal to that of a hydrogen atom, insulin molecules are 6 kDa, calcitonin are 45 kDa, laminin is 150 kDa. Named after John Dalton (1766 – 1844) who was an English chemist, meterologist and physicist.

Diaphragm pump - a positive displacement pump that uses a combination of the reciprocating action of a rubber or thermoplastic diaphragm and suitable valves to control inlet and outlet – advanced free floating diaphragm pump developed by and available as Clio and Euterpe and CerPhragm from www.pumpcell.com

Differentiation – A process by which a stem cell becomes a specialized cell type to perform particular tasks.

Dissolved Oxygen - DO - is a relative measure of the concentration of oxygen that is dissolved in the liquid medium / broth as a proportion of the maximal concentration that can be dissolved in that medium.

Disposable - refers to a product manufactured from typically materials preferably taken from the group of flexible, semi-rigid and rigid materials such as from the group of polymers, thermo polymers, thermo setting polymers, and elastic polymers.

DMEM - Dulbecco Modified Eagles Medium.

Down-Stream-Processing – DSP - bio processing, separation, purification steps following fermentation or cultivation from Up-Stream-Processing - USP.

E

E-beam irradiation – a high precision method of sterilization of various products. Electron beam processing involves irradiation (treatment) of products using a high-energy beta electron beam accelerator known as a “Rhodotron” or Dynamitron” from Belgian IBA. Such E-beam equipment can be turned on or off as any other industrial electrical equipment. This irradiation method precision is very high and damages the polymeric products minimal. Product temperature increase is only 8-10°C per 10 kGy load. Service providers among others are  - www.sterigenics.com or www.herotron.com or www.bgs.eu

E. coli - Escherichia coli - is the most widely studied prokaryotic model organism and an important species in the fields of  biotechnology and microbiology, where it has served as the host organism under fermentation in fermentors for the majority of work with recombinant DNA.

E&L - Extractables & Leachables - All materials have extractables and potential leachables. Check out under each.

ELISA = Enzyme-linked immunosorbent assay = a test to measure the concentration of antigens and antibodies.

Embryonic Stem Cells - ESC - can only be derived from embryos and caused lots of controversy surrounding their use. Undifferentiated cells derived from a pre-implantation embryo (inner cell mass of blastocyst) that are capable of self-renewal and can develop into cells and tissues of the three primary germ layers. The discovery of Induced Pluripotent Stem Cells have more or less exchanged the use of ESC.

Embryoid Body - EB - aggregate of cells derived from Embryonic Stem Cells. Upon aggregation, the cells spontaneously differentiated into multiple cell types derived from the three germ layers, recapitulating embryonic development.

Envelope - defines a space or a volume surrounded by a membrane or a wall of which some parts of the wall(s) are porous said envelope allow enclosure for a variety of growth bodies and/or matrix materials. Said porous walls allow a liquid and micro-organism to pass but not the growth bodies and/or matrix materials to escape from the envelope enclosure. Said envelope(s) are further containing inside a compartment. Said compartment are further contained inside a vessel.

Enzymes – proteins that catalyse biochemical reactions by causing or speeding up reactions without being changed in the process themselves.

Expression - refers to production or secretion of molecules such as proteins by micro organism being cultivated, but not to production of micro-organism by multiplication or proliferation or by fermentation.

Extractables - Chemical compounds that migrate from any product-contact material (including elastomeric, plastic, glass, stainless steel, or coating components) when exposed to an appropriate solvent under exaggerated conditions of time and temperature.

Express – to translate a cells genetic information, stored in its DNA, into a specific protein.

Extra-cellular – when a mammalian cell express a molecule through the cell membrane into the surrounding media

Eukaryotes - living cells with a cell membrane such as mammalian cells, human cells, stem cells, insect cells.

Euterpe - a Single-Use-Pump concept available from company PumpCell able to replace the peristaltic pump, centrifugal pump, high cost membrane pumps

F

FDA - Food and Drug Administration is a federal agency of Unites States of America department of Health and Human Services. FDA is responcible for protecting and promoting human health through regulations and supervision.

Fed-batch - refers to operation of a bioreactor to which fresh medium is added and no cultured liquid removed until after termination of the process.

Feeder cells - refers to a coating on a surface with an adherent type of cell that synthesizes the extra cellular matrix and collagen or fibroblast on top of which other cells, such as stem cells semi-adhere or agglomerate to.

Fermentation - refers to hosting of micro-organisms or single-celled living creatures for industrial purposes in a metabolic process creating a product. Typically bacteria or yeast are used for fermentation purposes.

Fermenter - means a physical device, a Stirred-Tank-Reactor, a container, a bag, a vessel which support biologically active environment suitable for cultivation of micro- organism, such as bacteria, yeast, algae, fungus performing a desired process where the micro-organism are populated inside  a compartment.

Film - refers to thermoplastic film or foil made using an extrusion process typically in one or several layers of different material for different purposes. Films may be permeable or impermeable and translucent or coloured in thickness less than 1 mm

Filter - means a processing device which by size exclusion separates particles suspended in a fluid in a method named filtration.

Filtrate - refers to the part of a suspension that passes through a filtration process, also called permeate.

Filtration - refers to mechanical separation, size exclusion, fractionating of solids from fluids, such as liquids or gases, by passing the feed stream through a porous material such as a porous, fibrous or granular substance, which retains selected solids and allows other solids and desired fractions of the fluids to pass through. Membrane filter products such as micro-filtration, ultra-filtration, nano-filtration, dia-filtration, gel-filtration are well known involving operation methods such as dead-end filtration, cross-flow filtration.

Fluid - means liquids as well as gases.

G

Gamma irradiation – low precision sterilization method for killing microorganisms like fungi, bacteria, viruses, spore forms by breaking down bacterial DNA, inhibiting bacterial division in pharmaceutical products. Often long lived, also for humans highly dangerous gamma-ray emitting isotopes, such as Cobalt-60 are used. Rough to plastic materials as to low dosing accuracy. The energy of gamma rays, as electromagnetic quantum waves, is similar to light, but with higher photon energy and shorter wavelength.

Gas volume – sparging, aeration gas “volume gas per unit of media volume per hour” (vvh) is a general measure ranging around 0.1-1 for mammalian cell cultivation to factor of 2-100 for microbial fermentation.

Glass - a transparent silica (Silicon Dioxide, SiO2) based non-crystaline amorphous brittle and solid material often with excellent corrosion resistance.

GMP – Good Manufacturing Practices - are the practices required in order to conform to the guidelines recommended by agencies that control authorization and licensing for manufacture and sale of food, drug products, and active pharmaceutical products. 

GLP - Good Laboratory Practises - CFR 21 part 58 refers to practices defined by the USA Food and Drug Administration for conducting nonclinical laboratory studies that support or are intended to support applications for research or marketing permits for products regulated by the USA FDA.

Growth bodies - refers to micro beads, macro carriers, micro carriers, loosely packed fibres, fibres in general, non-woven, grains, spheres, Rasching bodies or fibrous bodies or rigid or semi rigid foam blocks either packed inside envelopes, or suspended inside envelopes

H

Harvest – the product part of the broth being the expected product generated by micro-organism being cultivated in a bioreactor or fermented in a fermenter.

Head Space Volume – the difference in Volume between Working Volume (WV) and Vessel Volume (VV).

HEKHuman Embryonic Kidney cell, such as the adherent HEK 293 cells, easy to grow and transfect very readily, widely-used in cell biology research for many years. They are also used by the biotechnology industry to produce therapeutic proteins and viruses for gene therapy. Developed by Alex van der Eb in 1973.

Hollow-Fiber-Filter - HFF - is a membrane device that can serve to transfer gases, hydrophobic vapours, selected particles between two fluids. Often a device made from an outer rigid wall tube with end covers housing inside a bundle of thin wall tubes fabricated from porous material such as polyethersulfone or other polymers. The bundle of straws, tubes are sealed, cast into the end covers separating the tubes inside from the tubes outside and hereby appearing as a Cross-Flow-Filter (CFF).

Human Mesenchymal Stem Cell - hMSC - are a self-renewing population of adherent, multipotent progenitor cells that can differentiate into several lineages.

Human Induced Pluripotent Stem Cells - hiPSC can be generated directly from adult mammalian cells. The hiPSC technology was pioneered by Shinya Yamanaka, who showed in 2006 that the introduction of four specific genes encoding transcription factors could convert adult cells into pluripotent stem cells. He was awarded the 2012 Nobel Prize along with Sir John Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent."

Hybridoma – a hybrid mammalian suspension cell originating from B-cells, special white blood cells producing monoclonal antibodies. Cell size typically 14 µm, surfaces of hydrophobic character. The antibodies produced by the hybridoma are all of a single specificity and are therefore monoclonal antibodies. The term Hybridoma originates from Leonard Herzenberg (1931 – 2013).

I

iCORE = is a Personalized Medicine Perfusion-SUB based on carefully selected and arranged fibrous scaffold. The iCORE operates as 4, 8, 12 P-SUBs in parallel and works with existing PCS from Eppendorf and from PALL. A development product designed for the OD 110 mm bioBLOCK and iCELLis Nano developed by company PerfuseCell and ElectroSpin with financial support from Eurostar-Eureca.

IEC = International Electrotechnical Commission = an international electrical standards body. The standard we use is 60320 devided into "C13 female socket" and "C14 male plug" type of connectors. For security reasons C13 supply power and C14 receiver power.

InCyte - viable cell density measurement sensors based on capacitance available from Hamilton Company.

IgG = Immunoglobulin G = an antibody molecule and the most common type of antibody circulated in mammalian bodies.

Immobilized micro-organisms – such as adherent mammalian cells attached to a surface. The opposite of mobilised cells kept in suspension.

Immunology - is a branch of biomedical science that covers the study of immune systems in all organisms.

Immune reaction - antibodies in the body are in balance, until an antigen disturbs the balance, stimulating the immune reaction. Theory originating from Niels Kaj Jerne.

Impurities - refers to any substance that is not part of the biologic product, such as virus, HCP, DNA, RNA, Endotoxin

Impeller – rotating device at low speed insuring agitation via radial/axial movement of a fluid in a bioreactor (turbines are rotating devices in a fermenter)

Inoculate – to introduce cells into a culture medium or bioreactor.

Insect cells – such as Sf9 and S2 are cultivated in serum free media often at 25-28°C and pH 6-7 and size ranging 9-10 µm are efficient in expression of eukaryotic containing proteins.

Intra-cellular – when a micro-organism produce a product, which do not pass the micro-organism membrane and said micro-organism membrane must be destroyed in order to get the product out.

In vitro – performed using laboratory apparatus for testing rather than a living animal.

In vivo – involving living animals or humans as test subject.

Ion-exchange - refers to the exchange of ions between molecules, a solutions and a complex in the form of an insoluble sorbent, resin with typical physical appearance as beads or a membrane. The trapping of anions/cations takes place only with simultaneous releasing of other anions/cations; thus the process is called ion-exchange.

Irradiation - is the process by which an object is exposed to radiation. If administered at appropriate levels, all of these forms of radiation can be used to sterilize objects, a technique used in the production of medical instruments and disposables. The irradiation dose is usually measured in Gray. Where 1 kGy and is the radiation required to deposit 1 joule in 1 kilo matter. Levels of exposure for single-use pharmaceutical object are often less than 40 kGy. Survival fraction of the microorganisms is reversely proportional with the absorbed dose. Doses for sterilization should be chosen according to the initial bio burden, Sterility Assurance Level (SAL) and the radio sensitivity of microorganisms.

L

Lachesis - the Drive Unit for a variant of the CellMembra Perfusion-Single-Use-Bioreactor as available from www.perfusecell.com.

LAF - Laminar-Air-Flow bench, Laminar-Flow-Cabinet, Hood is a carefully enclosed bench designed to prevent contamination of biological samples.

Laminin – a group of large protein (150 kDa) cell culture growth in mammalian bodies and as growth support for human embryonic stem cells, induced pluripotent stem cells and primary cell growth.

Leachables – Chemical compounds, typically a subset of extractables, that migrate into a drug formulation from any product contact material (including elastomeric, plastic, glass, stainless steel, or coating components) as a result of direct contact under normal process conditions or accelerated storage conditions. These are likely to be found in the final drug product.

Luer-Lok - a standardized system of small-scale fluid fittings used for making leak-free connections between a male-taper fitting and its mating female part on medical and laboratory instruments, Named after the 19th century German medical instrument maker Hermann Wülfing Luer and now defined in the ISO 594 standard.

Lysis – disruption or breaking of the cellular membrane or cells by chemical, enzymatic or mechanical means.

M

MAb – monoclonal antibody, a highly specific, purified antibody that recognizes only a single epitope.

Macro carriers - micro-organism supporting device allowing cultivation of adherent depending micro-organisms. Size range typical from 2,000 to 10,000 µm composed by polymeric materials such as polystyrene or glass and may further be functionalized with one or more surface treatments and / or coatings.

Macro pore size - are ranging between 10-500 µm in diameter.

Magnetic-Stirrer-Table - MST based on excitation or 2, 4 or more permanent magnets rotating around an axle driven by a motor.

Magnetic strength - in general the magnetic field of permanent magnets drops off more or less exponentially over distance. This means a drop to 10% of power when increased distance a factor of 10. You can get more info here www.intemag.com/magnetic-materials-faqs

Mammalian cell – are eukaryotes, such as CHO, VERO, BHK21, HEK293, cell size often ranging between 15-25 µm, thin cell membrane and shear sensitive, doubling time during cultivation in a bioreactor is typically 24 hours, products are usually extracellular, can produce very large molecules, produce glycosylated proteins, produce humanized antibodies.

Matrix - defines a permeable body, a porous body, such as a 3D scaffolding structure such as a non-woven fibre based material or packed fibres in general or constituting growth bodies or any combination enclosed in envelope(s). Said matrix internal surface may further be functionalised with one or more coatings for improved micro organism adherence. Reference is also made to “growth bodies”, "scaffold" and to “micro carriers”.

Media, growth media and nutrient – are used interchangeable and refers to a mixture containing mostly water, carbon sources, various gases such as oxygen, nitrogen, carbondioxide and additives from the group of; vitamins, hormones, growth factors, plant hydrolysates, animal serum, antibiotics, antioxidants, antifoams, cell stabilizers and other components for cultivation of micro organisms.

Membrane - refers to a boundary layer, which serves as a selective barrier and remains impermeable to specific particles, molecules, substances or growth bodies or micro-organisms when exposed to the action of a driving force.

Mesenchymal Stem Cell - MSC - are connective tissue cells of any organ. MSCs, are multipoten which means they can differentiate into a variety of cell types.

Meso pore size - are ranging between 1-10 µm in diameter.

Metabolites – chemical products of metabolism, the chemical process of life.

Micro pore size - are pores ranging below 1 µm in diameter.

Microbial fermentation – process involving the use of micro-organisms, such as E.coli, to produce a small molecule or other substance.

Micro carriers - is a micro-organism supporting device or particle allowing cultivation of adherent depending micro-organisms. Size range typical from 200 to more than 1,000 µm composed by gelatine, collagen, cellulose or glass and may further be functionalised with one or more coatings.

Micro-organism, microbial cell, cells or biological cells are often used interchangeable and is typically divided into living single-celled organisms, microbes such as; fungus, algae, moss, plankton, yeast, protozoa, eukaryotes, prokaryotes, archaea, micro animals, extramophiles and plant cells or the like – 1. eukaryotes are living cells such as animal cells, insect cells, mammalian cells, human cells, stem cells some adherent or semi adherent or suspended – 2. prokaryotes are a variety of bacteria such as E.coli or the like – most of the above generically modified to solve specific tasks and product needs.

Mixing time – a parameter for assessing mixing efficiency in a fermenter. Mixing time to achieve a given degree of homogeneity in the broth.

Mole – the amount of a substance that contains the same number of elements (such as atoms, molecules or ions) as there are atoms of carbon in 12 grams of carbon-12.

Monoclonal Antibody - MAbs - the production of monoclonal antibodies by a homogeneous population of clonal cells. MAbs was discovered by César Milstein (1927-2002) and Georges J. F. Köhler (1946-1995) in 1975. They shared the Nobel Prize of 1984 for Medicine and Physiology with Niels Kaj Jerne (1911-1994), who also made contributions to immunology. The first MAb medicine became available late 1980ties. As of 2016 there is less then 50 MAbs approved by FDA and more than 100 candidates in clinical trials. see www.nature.com

MpC – Magnet-pole-Centre refers to the diameter in which the maximum magnetic force is available on stirrer, turn tables, Magnetic-Stirrer-Tables.

MRC-5 - cell line composed of fibroblast derived from lung tissue of an 14 week old aborted caucasian male fetus. MRC-5 cells are used to produce several vaccines. The cell line was isolated by J.P. Jacobs and colleagues in September 1966.

Multi-potency – The ability of cells to develop into more than one cell type of the mammalian body. Multi-potent cell types in the body comprise lineage-committed progenitors, including organ specific adult stem cells.

N

Non-woven - refers to a 80 - 99% porous sheet, felt, scaffolding or web made from mono size or mixed size fibres with diameter ranging 1 - 100 µm in diameter, bonded together by, thermal and/or chemical and/or mechanical methods, which are neither woven nor knitted forming pores ranging 1 - 500 µm in size.

Newtonian fluids – are fluids of one material with even viscosity homogeneously through the fluid and linear with change in internal shear forces, friction like with increased velocity vector.

Non-Newtonian fluids – are fluid of mixed materials with different specification of non-linear internal shear forces, friction with changing velocity vector. In bioprocessing fermenters the broth is often pseudo-plastic with viscosity decreasing with increasing shear = RPM.

Nylon - is a generic designation for a family of synthetic polymers known generically as aliphatic polyamides. The first example was Nylon 66 produced on February 28, 1935, by Wallace Carothers (1896-1937) at DuPont´s research facility in USA. In general excellent corrosion resistance.

O

Oxygenator - or aeration refers to a sparging unit, bubble unit, a device or method for oxygen and/or carbon dioxide exchange from media to external sources.

Optical Density - OD - a spectrophotometric measurement of light scattered by a suspension at a particular wavelength. Optical Density / OD measurements can be used to determine the biomass concentration. In practice also know as "turbidity" where the suspended particles reduce the light passing from the light source to the receiver.

P

PAT - Process Analytical Technology - has been defined by FDA as a mechanism to design, analyze, and control pharmaceutical manufacturing processes.

PBS - Phosphate Buffered Saline - used to wash SUBs and sensors with.

PCS – Process-Control-System - a digitally operating computer used for automation of typically industrial electro mechanical processes, such as control of STR, SUBs, SUFs via sensor input and actuator output. Such as supplied by a app 25 global manufacturer with the purpose to gather sensor data and adjust the process variable continuously in bioreactors and fermenters. About 45.000 such highly proprietary and all identical PCS has been manufactured the last 50 years. All with few sensor input being DO, pH, temperature, and media level in general limiting understanding of the processes.

Perfusion mode operation - refers to a method or principle for operating a bioreactor, the media are sequentially exchanged, fresh nutrients added, used media removed and the crude product is harvested throughout the culture period, typically 2 – 10 times longer than batch process operation time. Such as all single-use CellMembra available from www.perfusecell.com

Perfusion - cell retention perfusion = protein expression based on; 1. sequential removal of harvest of product from micro-organism, 2. sequential removal of micro-organism, 3. sequential media addition. Such product available from www.perfusecell.com

Perfusion-Single-Use-Bioreactor - P-SUB - such as the CellMembra product available from www.perfusecell.com

Peristaltic pump - defines a type of positive displacement pump used for pumping a variety of fluids. The fluid is contained within a flexible tube fitted inside a circular pump casing. A rotor with a number of "rollers", "shoes" or "wipers" attached to the external circumference compresses the flexible tube locking liquids inside a defined moving volume against the inner surface of a circular housing. 

Permeable body - defines a matrix, a scaffolding, a volume containing porous materials, a porous body, a packed bed of growth bodies, a porous wall.

Permeate - the parts of a liquid mixture that is allowed to pass a filter, porous membrane, permeable body.

PG 13.5 - is a measure of threaded size classical sensor mechanical connectors and PG is the technical standard known as Stahl-Panzer-Rohr-Gewinde.

Pluri-potency – The ability of a cell to give rise to all different cell types of the body, but not extra-embryonic tissues. Pluripotent Stem Cells include ESC, iPSC cells and hiPSC.

Pluripotent Stem Cells - are stem cells that have not yet ‘decided’ what final cell to become. The discovery of Induced Pluripotent Stem Cells have completely changed the perspective of the use of stem cells. Pluripotent Stem Cells hold great promise in the field of Regenerative Medicine. 

pH – power of hydrogen or the log of the concentration of H+ ion in a solution.  Søren Peder Lauritz Sørensen (1868-1939) was a Danish chemist, famous for the introduction of the concept of pH, a scale for measuring acidity and basicty. The pH symbol has roots in the French "pouvoir hydrogene" (power of hydrogen).

pH sensor - a device based on manufactured, offered by a variety of suppliers in different dimensions with 3-4 different principle of connectors. Dimension used

Plasmid - a small DNA molecule within a cell that is physically separated from a chromosomal DNA and can replicate independently. Plasmid is a genetic elements that exist exclusively or predominantly outside of the chromosome and can replicate autonomously. Plasmid are the most-commonly used bacterial cloning vectors. First described by Joshua Lederberg in 1952.

PolarWellis the pre-installed non-invasive DO well in the customizable CellVessel SUBs designed for super simple installation of polarographic DO sensor's avoiding sensor autoclaving. Manufactured by CerCell.

Polishing - refers to the final purification step(s) involving an affinity or other refined chromatography methods.

PolyCarbonate - (PC) belongs to the group of thermoplastic polymers. PolyCarbonate were first discovered in 1898 by the German scientist Alfred Einhorn (1856-1917). Unlike most thermoplastics, polycarbonate can undergo large plastic deformations without cracking or breaking. As a result, it can be processed and formed at room temperature using sheet metal techniques. PC should not be used in contact with alkaline, alkali salts, amines and high ozone, acetone and xylene concentrations. Ketones, esters causes severe crystallization.

Polyclonal Antibodies - PAbs - represent a population of antibodies collected from multiple B cell clones that have been activated by the immune response of an immunized animal. The antibody are produced in animals such as chickens, goats, guinea pigs, hamsters, horses, mice, rats, and sheeps being injected with a specific antigen that elicits a primary immune response.

elicits a primary immune response
elicits a primary immune response
elicits a primary immune response
elicits a primary immune response

Polyamid - occur both naturally and artificially (Nylon). Examples of naturally occurring polyamides are proteins, such as wool and silk.

Population - describes the numbers of micro-organisms (such as mammalian cells being 15 - 18 µm in size when suspended in a liquid) which range typically from few hundreds to a maximum of app 3-400 million per cm3 of spherical mammalian cells when centrifuged to maximum solids content from a suspension = highest possible mass. Other micro-organism will have different size and corresponding different maximum population number.

Pores - describe cavities or open spaces in a porous material expressed in micron size, such as 50 µm pore size.

Porosity - refers to a measure of the void spaces in a porous material expressed in percent 0 - 100%.

Power Number- is dimensionless parameter used for estimating the power consumed by the mixing turbine. The lower number the better! The typical used Rushton turbine has a high Power Number and opposite the Smith or Bakker turbine has a lower Power Number under same conditions.

Power consumption – the power or kinetic energy expressed in kW/m3 possible to loose, dissipated in agitation, in the broth in a fermenter ranging 50 kW/m3 in small fermenter to 10 kW/m3 in large fermenters. The full calculation also include energy for supplying compressed gas and for refrigeration.

Pre-sterilized – the particular product are enclosed in dual plastic foil bags and exposed to methods which insure the bag content is sterile. The product is then supplied in said dual bags to the end-user. The end-user hereby avoids the troublesome high temperature sterilization of the re-usable equipment and takes advantage of the single-use capability.

Proliferation - refers to a fast increase in numbers of a similar substance, a fast unlimited doubling, re-production, division of identical micro-organism, multiplication of the micro-organism or substance.

Protein - refers to complex organic macromolecules often primary ingredient in therapeutic medicine further proteins are present in each living cell of all organisms without exceptions and in the cells, the proteins are abundant in variety or types.

P-SUB - Perfusion-Single-Use-Bioreactor refer to a SUB in a setup for perfusion mode operation.

PTF – Pulsating-Tangential-Flow – a method of perfusion operation for continues cultivation under non-steady-state conditions. Sequentially a portion of the broth is taken from the bioreactor and forced along the semi-permeable membrane (CFF) in one direction. The PTF method characterized by its inherent ability to reduce filter deposits by selective broth velocity through the CFF. The membrane insure that high cell densities are kept inside the bioreactor broth and the CFF allow the product to pass the membrane. The Single-Use technology developed by www.stobbe.com and marketed as CellMembra by www.PerfuseCell.com

Purification - means a central part of the Down-Stream processing that takes a crude supernatant or cell homogenate (chaotic slurry of tissue and cells) and up-concentrates, isolates the biologic product in a fairly pure form. Involves processes such as filtration and chromatography in several difference form.

Q

Quality-by-Design - QbD - concept originates from Joseph Moses Juran (1904-2008). Juran's process seeks to create features in response to understanding customer needs. These are customer-driven features. The Quality by Design model consists of the following steps:

  1. Establish the project design targets and goals.
  2. Define the market and customers that will be targeted.
  3. Discover the market, customers, and societal needs.
  4. Develop the features of the new design that will meet the needs.
  5. Develop or redevelop the processes to produce the features.
  6. Develop process controls to be able to transfer the new designs to operations

R

Raschig rings - are pieces of tube (approximately equal in length and diameter) used in large numbers as a packed bed within columns for distillations and other chemical engineering processes. Provide vastly improved surface area inside said column. Named after their inventor, the German chemist Friedrich Raschig (1863 - 1928). 

Regenerative Medicine - reconstruction of diseased or injured tissue by tissue engineering and molecular biology, which deals with the "process of replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function.

Retentate – the parts of a mixture such as particles, “micro-organisms” of a mixture or feedstock that is held back by a “membrane”, and do not pass the membrane as to its size, shape or charge. 

Reynolds number - is a dimensionless number that is used to help predict similar flow patterns in different fluid flow situations. Reynolds number are also used to characterize different flow regimes within a similar fluid, such as lamianr or turbulent flow. Laminar flow occurs at low Reynolds numbers, where viscous forces are dominant, and is characterized by smooth, constant fluid motion; turbulent flow occurs at high Reynolds numbers. Named after Osborne Reynolds (1842–1912).

Rotameter - means an instrument that measures the volume or mass flow rate of a liquid or gas. Also know as a variable area flow meter being a transparent and conical tube part with a floating body inside. Operated with gravity when arranged vertical and against a spring when operating horizontal.

RPM - Revolutions per Minute.

RTD - Resistance-Temperature-Detector type of sensor which comes as Pt100 or Pt1000. Measure temperature by correlating the resistance of the RTD element with temperature. Most RTD elements consist of a length of fine coiled wire (Platinum) wrapped around a ceramic or glass core. The element is usually quite fragile, so it is often placed inside a sheathed probe to protect it. Pt100 show 100 and Pt1000 show 1000 Ω at 0°C.

RUS - Re-Usable-Sensor supplied from a range of manufactures.

S

Scaffolding – is a structure of fibers, materials creating a porous, open structure with large internal surface area for hosting typically mammalian cell lines.

Semi-permeable membrane - a membrane that will allow certain molecules or ions to pass through it by diffusion such as a hollow-fiber-membrane.

Sensor - refers to devices able to measure on-line quality process variables associated within a given process. Available for in liquid or in gas measurements. Such as the level of pH, dissolved oxygen (DO), bio mass / cell density, conductivity, dissolved carbon dioxide, lactate, glucose, glutamine, glutamate, ammonia, pressure, liquid level, fluid flow/ mass-flow, velocity, temperature, etc. Sensors in general are available as either RUS or SUS.

Separation - means dividing fluid borne particles of different size by membrane filtration or centrifugal separation based on particle size, mass difference into at least two separate particle containing fluid streams further separation by affinity adsorbing the target compound.

Secreted product – the Angstroem size product from a micro-organism such as hormones, proteins secreted extracellularly or expressed through the micro-organism, cell wall.

SLS - Selective Laser Sintering is an Additive Manufacturing (AM) technique that uses a laser as the power source to sinter powdered solid nylon material, aiming the laser automatically at points in space defined by a 3D model, binding the material together to create a solid structure.

Septum - is a wall, dividing a cavity or structure into smaller ones. Such as a round rubber wall mounted in the head plate of a bioreactor or fermenter. Used for inoculation by forcing a syringe needle through the wall injecting a liquid.

Serum – from blood of mammalians is the component that is neither white nor red blood cells, clotting factor (coagulation) and plasma. Serum includes all proteins not used in blood clotting (coagulation) and all the electrolytes, antibodies, antigens, hormones, and any exogenous substances. Historically, serum was the first source of PolyClonal Antibodies. Anti-serum is made by injecting an antigen into an animal, most commonly a rabbit or a chicken (sometimes to bypass the problems of tolerance) but also hamsters, rats, goats, and even cows

Shear force – two materials or bodies being pushed in opposite directions, fragile micro-organisms may be damaged when exposed to large shear forces.

Single-Use - refers to a product designed for use only once and to be disposed after use typically delivered pre-sterilized, irradiated and ready to use.

SIP – Sterilization-in-Place, use steam to clean and sterilize equipment or systems without moving them from their installed location.

Spallation – a non-desired process, where materials, like small rubber particles, fragments originating from hoses, such as hoses used in peristaltic pumps, as to hose-to-hose wall impact and stress. The Euterpe and Mnemosyne pump from www.pumpcell.com avoid this problem.

SSB – Stirred-Suspension-Bioreactor.

Steady state conditions - a method if operating a bioreactor where most compounds, such as nutrients concentrations and biomass is maintained at constant concentrations for endurance time. Typically obtaining higher output of product and improved product quality.

Sterile – absolutely free of any micro-biological contamination.

STR – Stirred-Tank-Reactor refer to an old fashion bioreactor or fermenter seen from a range of supplier manufactured in glass and stainless steel.

Stainless Steel - refers to an alloyed metal based mostly on steel, nickel, chromium, vanadium, carbon characterized with excellent corrosion resistance. AISI316L is eqivelant to DIN 1.4404 Stainless Steel and more or less the only used in the pharma industry.

Stem cells - cells found in all multi cellular organisms. They are characterized by the ability to renew themselves through mitotic cell division and differentiate into a diverse range of specialized cell types. Stem cells are in general; Embryonic Stem Cells, Pluripotent Stem Cells, induced Pluripotent Stem Cells, adult (somatic) stem cells in general, regenerative stem cells, tissue-derived stems cells, stromal vascular fraction stem cells or the like.

Stem cell treatment - of current international interest originate from humans and not from human primates. See www.eurostemcell.org

SUB - Single-Use-Bioreactor refer to film bag(s) or rigid plastics bioreactor pre-installed with a agitation device and one or more “Single-Use-Sensors” all manufactured from disposable materials and delivered somewhat pre-sterilized and hereby ready for use eliminating the traditional in-house heat sterilization. As seen from www.perfusecell.com and from www.cercell.com

SUF – Single-Use-Fermenter as BactoVessel seen from www.cercell.com

SUP - Singel-Use-Pump. A fluid conveying device manufactured at least partly from disposable materials. Such as a peristaltic pump or a diaphragm pump or a direct gas-to-liquid surface driven pump or the like comprising disposable wetted part and re-usable non-wetted parts. Such as Air-Operated-Diaphragm-Positive-Displacement Single-Use-Pump's seen from www.pumpcell.com

Supernatant – the opposite of precipitant, which are the two different products which is obtained after centrifuge of a suspension, often the liquid component that has the lowest density or cleaned from debris and cells.

SUS - Single-Use-Sensor being more or less the opposite of RUS. A disposable devices able to on-line measure analysts, fluid concentrations and deliver a signal, such as an electrical signal relative to the concentration measured. The in-expensive SUS is designed primarily from polymeric materials to be pre-installed in a SUB or SUF for simultaneous sterilization in dual film bags for convenience to the end-user who then avoid sterilization before use. Seen from www.cercell.com

Suspension – a mix of liquid and non liquid solid mater kept floating in a solution.

Suspended - refers to particles, artificial particles, micro-carriers such as “micro-organism” depending on being preferably homogeneous suspended or mobilized in liquid in the STR.

Suspension - refers to micro-organism suspended in a fluid with no or weak affinity to adhere to surfaces, such as  micro-organism of semi-adherent or of non-adherent character, though willing to agglomerate, willing to semi-adherent to similar or micro-organism, willing to semi-adherent to different micro-organism by agglomeration or by other forces.

T

Tangential-Flow-Filtration – TFF - A separation method that transfers components of one system into another.

Titer – is a way of expressing concentration, a measured sample typically a product expressed by micro organism.

Totipotency – The ability of the cell to give rise to all cell types of the body and extraembryonic tissue. The zygote is totipotent.

Trypsin – an enzyme capable of cleaving peptide bonds. Is used to remove adherent cells from a surface and to break up purified proteins for analysis. Such as remove the binding of stem cells to surfaces.

Turbine - a high speed rotating device, a fluid-agitating element equipped with symmetrical arranged blades or vanes rotating inside a liquid filled fermenter at high speed for agitation, mixing of various fluids, and delivery of kinetic energy. (The impeller rotate inside a bioreactor at low speed)

Turbine flooding – turbine design and speed creates the phenomenon where added gasses in form as bubbles reach a pressure lower than the broth pressure and burst as to the low pressure changing the physics of the broth. Rushton turbine is prone to flooding where Smith is far better and Bakker the best know turbine design avoiding flooding.

Turn table – also known as a Magnetic-Stirrer-Table (MST) based either on excitation or 2, 4 or more permanent magnets rotating around an axle driven by a servo motor. Such MST available from www.cercell.com

U

UniVessel – a non-customizable polycarbonate Single-Use-Bioreactor in one size of 2,6 litre Vessel Volume for cultivation of various cell lines in suspension manufactured by Sartorius.

Unipotency – The ability of a cell to develop into only one type of cell or tissue.

Unit of Pressurewe use SI / International System of Units or commonly known as Metric Units such as Pascal or kPa or Bar or milliBar.

Up-Stream-Processing - USP – the function associated with a bioreactor operation before the Down-Stream-Processing.

V-W

Vaccines – preparations that elicit an immune response to protect a person or animal from a disease causing agent.

Vacuum - Vacuum is measured in Units of Pressure relative to ambient atmospheric pressure on Earth or in units of pressure above absolute zero pressure. For Units of Pressure we use SI / metric units such as Pascal or kPa or Bar or milliBar.

VERO cells – kidney cells extracted from an African green monkey (larger than CHO cells). The original cell line was named "Vero" after an abbreviation of "Verda Reno", which means "green kidney" in Esperanto.

VisiFerm - is the optical oxygen (DO) sensor with integrated opto-electronics, having the full functionality of a measuring device with selfdiagnostics. Works perfect combined with the VisiWell insert in the CellVessel SUBs. Manufactured by Hamilton.

Virus – the simplest form of life.

VisiWell - is the pre-installed non-invasive DO well in the customizable CellVessel SUBs or BactoVessel SUFs designed for super simple installation of the VisiFerm DO sensor avoiding autoclaving. Manufactured by CerCell.

Viscosity – Viscosity is a measure of a liquids resistance to gradual deformation expressed at 25°C in Pascal/second or derived centiPoise, such as honey which is 2-10 Pa· or 2,000-10,000 cP.

VV – Vessel Volume, total volume of a STR, SUB, SUF, difference between Working Volume and Head Space Volume. VV = WV+HSV.

WV – Working Volume refers to the actual media volume a STR, SUB or SUF operate within. Typically 70-90% of Vessel Volume. Determined by various factors, such as: serum content in media, use of anti-foum agent, areation volume, agitation speed, planned cell density, etc.

Y

Yeast – a single-celled fungus highly useful for fermentation and expression of a huge variety of products, such as ethanol.

Young's modulus or modulus of elasticity - is a measure of the stiffness of an elastic material and is a quantity used to characterize materials. It is named after the 19th-century British scientist Thomas Young (1773 – 1829).

 

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