Midterm Flashcards

1
Q

Define industrial bioprocessing (biotechnology)

A

any commercial technique that uses living organisms or substances from those organisms to make or modify a product, to improve plants or animals, or to develop microorganisms for specific uses

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2
Q

When did Van Leeuwhenhoak observe yeast cels in alcohol fermentation?

A

1680 AD

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3
Q

What are the 3 stages of industrial bioprocessing?

A
  1. upstream processing
  2. fermentation
  3. downstream processing
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3
Q

Define allogeneic

A

cells from antigenically-matched donor

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4
Q

What are the 5 common properties of all industrial bioprocesses?

A
  • produce a product in demand and has value
  • active cells should function as intended consistency from batch to batch
  • raw materials used to grow the cells should also be consistent and a high quality
  • process steps should be consistent
  • product should meet critical quality attributes (CQA) and be stable under shipping/storage conditions and maintains quality
  • cost of goods (COGs) to make product should be low enough to make projected profit
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5
Q

Define autologous

A

cells from patient to be treated

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7
Q

When did Cagniard-Latour, Schwann, Kurtzing hypothesize living cells?

A

1837 AD

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8
Q

The did Pasteur show living yeast cells ferment sugar to ethanol and CO2?

A

1857 AS

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9
Q

When did Darwin publish the origin of species?

A

1859 AD

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10
Q

When did Pasteur note the relationships between microbes and disease?

A

1877 AD

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11
Q

When did Koch develop microbial technique and maintenance methods?

A

1881

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12
Q

When was the 1st commercial production of lactic acid by anaerobic fermentation?

A

1881

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13
Q

When did the UK produce acetone and butanol by anaerobic fermentation?

A

1881

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14
Q

When did Flemming demonstrate that mode contamination of bacterial cultures causes bacterial death?

A

1929

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15
Q

When did Florey & Chain isolate Penicillin, elucidated structure and demonstrated its bacterial properties on Gram positive bacteria?

A

1940

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16
Q

When did Watson and Crick discover double helix structure of DNA?

A

1953

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17
Q

When did Paul Berg & Colleagues isolate the first plasmid bacterial cloning vector and showed that it was self-replicating and separate from chromosomal DNA?

A

1971

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18
Q

When did Boyer and Cohen start collaborating to develop a method to enable bacteria to take up plasmid DNA?

A

1972

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19
Q

When did Boyer & Cohen isolate a new cloning vector pSC101 & create bacterial intra and inter species rDNA?

A

1972-1973

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20
Q

When did John Morrow and colleagues clone & propagate ribosomal DNA genes from a eukaryote in E. coli?

A

1973

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21
Q

When did Genetec start?

A

1976

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22
Q

When did Sanger dideoxycytidine chain-termination DNA sequencing method develop becoming a standard method?

A

1977

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23
Q

When did US supreme court rule that genetically engineered microorganisms can be patented?

A

1980

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24
Q

When did Genetec develop recombinant hGH in E. coli?

A

1981

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25
Q

When did Eli Lilly get 1st ever FDA approval of a recombinant product insulin (humulin) in E. coli?

A

1982

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26
Q

When did PCR developed by Kary Mullis at Cetus Corp. and would go on to revolutionize rapid DNA sequencing?

A

1983

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27
Q

When did Kohler and Milstein produce monoclonal Ab in hybridomas in and win a Nobel prize?

A

1984

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28
Q

When did recombinant met-hGH somatropin produced in E. coli buy Genetec approved in USA?

A

1985

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29
Q

When did orthclone OKT3 (muoromonab-DCD3) produced in hybridoma cell line was the first mAb approved by the FDA?

A

1985

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30
Q

When was the 1st recombinant drug made in CHO cells was tissue plasminogen activator and approved by the FDA?

A

1987

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31
Q

When was the first approved gene therapy clinical trial was carried out, resulting in partial rostral of immunity which was temporary?

A

1990

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32
Q

When was recombinant erythropoietin made in CHO cells by Amgen was approved by the FDA for anemia treatment by the FDA (brands Epogen and epocrit)?

A

1990

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33
Q

When was the first commercialized genetically modified crop tomato marked by cal gene?

A

1994

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34
Q

When was dolly the sheep the first mammal successfully cloned at the Roslin institute in Scotland?

A

1996

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35
Q

When were improvements in clonal stability/better vectors, media optimization and feeding strategies improved?

A

late 1990s - early 2000s

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36
Q

When was sequencing of the whole human genome completed?

A

2003

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37
Q

When was anti-thrombin the first recombinant protein produce din the transgenic animals/goats was approved by the EMEA?

A

2006

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38
Q

When was the first recombinant protein vaccine against Newcastle disease virus made in plant cell culture transgenic tobacco approved by the USDA?

A

2006

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39
Q

When was the Craig centre institute (California) created the first synthetic cell by inserting the genome of Mycoplasma mucoides into the empty cytoplasm of related bacterium?

A

2010

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40
Q

When was the whole genome sequence of CHO K1 was published?

A

2011

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41
Q

When was the first manufactured set cell product prochymial Osiris therapeutics approved by health Canada for GvHD?

A

2012

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42
Q

When were Spanish researchers successfully reprogrammed mouse stem cells into iPSD and were first to grow iPSC in pretri plates?

A

2013

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43
Q

When was Japanese health agency approve the first use of stem cells in human clinical trials?

A

2013

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44
Q

When was GINTUIT the first allogeneic cell-based product approved by the FDA?

A

2012-present

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45
Q

When was the first autologous and genetically modified t-cel treatment - personalized medicine?

A

2017

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46
Q

When was ALOFISEL the first allogeneic stem cell treatment approved in the EU?

A

2018

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47
Q

Define primary metabolites

A

metabolites produced during active growth (Trophophase) and required for growth and maintenance of cellular functions

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48
Q

Define secondary metabolites

A

metabolites which are not required for growth and maintenance of cellular functions and are an end product of the primary metabolism

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49
Q

What phase is secondary metabolites normally produced in?

A

stationary phase (idiophase)

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50
Q

Define cellular therapeutics

A

cells, single or multi-cellular on a matrix are the product

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51
Q

What are the phases of cell growth?

A

lag, exponential, stationary, death phase

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52
Q

Who developed ABE fermentation?

A

Chaim Weizman

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53
Q

What is a similarity and a difference of how ABE fermentation is carried out to how yeast ferments sugars for ethanol?

A
  • similar mechanism

- different that organisms are strictly anaerobic in ABE

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54
Q

What is the class of bacteria usually carrying out ABE fermentation?

A

clostridia

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55
Q

What are the 6 stages of the biopharmaceutical research and development process?

A
  1. basic research
  2. drug discovery
  3. pre clinical
  4. clinical trials (phase I, II, II)
  5. FDA review
  6. post-approval research & monitoring
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56
Q

What is the relationship between product value and volume?

A

high volume, low value product

low volume, high value product

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57
Q

What are the 6 things that determine the economics of fermentation?

A
  • cost of raw materials
  • utilities
  • labour and maintenance
  • fixed charges
  • working capital charges
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58
Q

When a product is in very high demand annually, what happens to the price?

A

decreases significantly

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59
Q

When the production cost is high, what is the fermentation titre?

A

low

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60
Q

When using high-quality materials, what happens to labour and depreciation costs?

A

both decrease (because need less purification)

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61
Q

What is the next step after the initial evaluation of market demand, cell titre vs. cost and value of certain bio products?

A

deciding on the cell expression system

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62
Q

What are the 10 important elements in choosing an industrial cell expression system?

A
  1. type of product
  2. route of product biosynthesis should be well characterized
  3. are you going to develop (growth conditions, metabolic engineering) an optimized cell line in-house, license out development, or license an existing cell production platform?
  4. cell line should be stable during the projected time course of a full-scale fermentation (upstream process) & also during dry-storage
  5. ability to grow in a low cost defined medium with limited addition of vitamins and other growth factors is a plus but not always possible (eg. mammalian cells)
  6. amenability to genetic manipulation is desirable, especially in the case of recombinant processes.
  7. safety, non-pathology and toxicity
  8. a cell line that has well-established regulatory acceptance in the industry is optimal (eg. E. coli, CHO)
  9. readily harvested from fermentation, if product is intracellular - readily breakable to release product
  10. acceptable cell-related impurities profile to make product purification easier (downstream processing)
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63
Q

What is the benefit to in-house development of an optimized cell line?

A

control over OP and R&D

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64
Q

What is the downside to in-house development of an optimized cell line?

A

takes longer

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65
Q

What is the benefit to licensing a cell production platform?

A

takes less time

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66
Q

What is the downside to licensing a cell production platform?

A

high licensing fees

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67
Q

Are mAb glycosylated?

A

yes

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68
Q

Are multivalent vaccine (flublok) glycolsylated?

A

yes

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69
Q

Is insulin glycolsylated?

A

no

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70
Q

Is a difficult to express protein glycosylated?

A

No/yes

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71
Q

Is immunotherapy glycosylated?

A

yes

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72
Q

Is regenerative medicine glycosylated?

A

yes

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73
Q

Is mAb a secreted product?

74
Q

Is multivalent vaccine (flublok) a secreted product?

75
Q

Is insulin a secreted product?

76
Q

Is a difficult to express protein a secreted product?

77
Q

Is immunotherapy a secreted product?

78
Q

Is regenerative medicine a secreted product?

79
Q

What cell type is used to produce mAb?

80
Q

What cell type is used to produce multivalent vaccine (flublok)?

81
Q

What cell type is used to produce insulin?

82
Q

What cell type is used to produce difficult to express protein?

83
Q

What cell type is used to produce immunotherapy?

84
Q

What cell type is used to produce regenerative therapy?

A

stem-cells

85
Q

What is a recommended cell/expression system for mAb?

A

CHO/fed-batch

86
Q

What is a recommended cell/expression system for multivalent vaccine (flublok)?

A

SF9/baculovirus vector/fed-batch

87
Q

What is a recommended cell/expression system for insulin?

A

E. coli/fed-batch

88
Q

What is a recommended cell/expression system for difficult to express proteins?

A

P. pastoris/fed-batch

89
Q

What is a recommended cell/expression system for immunotherapy?

A

human CAR-T/cell factory or fed-batch

90
Q

What is a recommended cell/expression system for regenerative medicine?

A

induced pluripotent see cells (iPSC)/cell factory or fed-batch

91
Q

What is the cell system rational for mAb?

A
  • well characterized
  • excellent yields
  • many regulatory approvals
92
Q

What is the cell system rational for multivalent vaccine (flublok)?

A
  • multiple proteins can be made
  • low immunogenicity
  • moderate # reg approvals
93
Q

What is the cell system rational for insulin?

A
  • well characterized
  • excellent yields
  • many regulatory approvals
  • cheap raw materials
94
Q

What is the cell system rational for difficult to express proteins?

A
  • excellent yields
  • human glycosylation, some strains
  • generally regarded as safe
  • cheap raw materials
95
Q

What is the cell system rational for immunotherapy?

A
  • CAR-T cells are product
  • specific targeting
  • autologous or allogeneic
96
Q

What is the cell system rational for regenerative medicine?

A
  • iPSC are product
  • cytodifferentiation
  • tissue replacement
  • personalized medicine
  • autologous or allogeneic
97
Q

What are 9 examples of targets for improving cell lines?

A
  • growth rate
  • genetic stability
  • non-toxicity to humans
  • cell size
  • ability to use cheaper substrates
  • modification of submerged morphology
  • elimination of production of compounds that interfere with downstream processing
  • permeability alterations to improve product secretion
  • tagging protein products
98
Q

What are some ways that make growth rate a target for improving cell lines?

A

optimizing growth rate by cell type or clone screening or culture conditions

99
Q

What are some ways that genetic stability can be targeted to improve cell lines?

A

plasmid expression vectors that are maintained efficiently during culture in bacterial cells, or integrate in a stable manner into transcription hot spots in genomic DNA of mammalian cells

100
Q

Why is cell size a target for improving cell lines?

A

larger cells are more easily separated from culture fluid at the end of culture, mammalian cells are easier to separate from broths than bacterial cells

101
Q

Why is the ability to use cheaper substrates a target for improving cell lines?

A

cells that use minimal medium are best for processing efficiency (process control, analysis)

102
Q

Who is the modification of submerged morphology mostly a concern for in improving cell lines?

103
Q

Define cell culture medium

A

a liquid or gel designed to support the growth of microorganism, cells or small plants

104
Q

How does cell culture media regulate the cell cycle?

A

because comprised of an appropriate source or energy and compounds to do that

105
Q

What are the 7 main factors that affect the final choice of individual raw materials for culture media?

A
  • cost and availability
  • ease of handling
  • sterilization requirements/potential denaturation
  • formulation, mixing, complexing and viscosity characteristics
  • levels and range of impurities
  • health and safety implications
  • thermal damage
106
Q

Why does cost and availability affect the final choice of individual raw materials for the culture medium?

A

ideally the materials should be inexpensive, consistent quality and year-round availability

107
Q

Why does ease of handling affect the final choice of individual raw materials for the culture medium?

A

associated with transport and storage costs (eg. temperature control requirements)

108
Q

Why are inorganic salts added to media?

A

helps retain the osmotic balance and help in regulating membrane potential by providing sodium, potassium, and calcium ions and ions for cell attachment and enzyme cofactorsW

109
Q

What are 3 things that are added to a media for metabolism (ie. building cellular structures)?

A

carbohydrates, nucleic acids, and amino acids

110
Q

Why are vitamins, trace elements and lipids added to media?

A

metabolism and enzyme function

111
Q

Define BSA

A

bovine serum albumin

112
Q

Why is BSA added to media?

A

ruch source of growth factors and appropriate for cell cloning and growth of fastidious cells

113
Q

What percentage does normal growth media often contain of BSA?

114
Q

What are the 8 functions that supplementation of media with fetal serum serves?

A
  • provides basic nutrients
  • provides growth factors and hormones (growth promotion and special cell function)
  • provides several binding proteins to carry other molecules into cel (eg. albumin, transferrin)
  • supplies proteins like fibronectin to promote attachment of cells to substrate and spreading factors to help cells spread out before division
  • provides protease inhibitors (protects from proteolysis)
  • provides minerals
  • increases viscosity of medium (protects cells from mechanical damage)
  • acts as buffer
115
Q

What are the 6 advantages of serum in media?

A
  • contains growth factors and hormones stimulating cell growth and functions
  • helps attachment of cells
  • acts as spreading factor
  • acts as buffer agent to maintain pH
  • functions as binding protein
  • minimizes mechanical damages through increasing viscosity
116
Q

What are the 5 disadvantages of serum in media?

A
  • lack uniformity in composition
  • testing needs to be done to maintain quality of each batch before using
  • may contain growth inhibiting factors
  • increase risk of contamination
  • presence of serum in media may interfere with purification and isolation of cell culture products
117
Q

Define CHO

A

Chinese hamster ovary

118
Q

Why are mammalian cell lines like CHO the prevailing animal-derived cell system?

A

due to their suitability to produce conveniently glycosylated proteins

119
Q

Define fermentation

A

cultivation of living organism or cells under controlled conditions to optimize growth and productions of products

120
Q

What is controlled to achieve maximum yield and efficiency for fermentation/cell culture processes?

A

environmental conditions

121
Q

How is optimization of fermentation/cell culture processes carried out?

A
  • taking into account different factors and the interaction of these factors
  • statistical approaches like factorial design are used to define model space for process control and operational space for parameters to reduce risk of process variability
122
Q

Define the Hayflick limit

A

the finite number of generations of growth and it is characteristic of the cell type, age, and species of origin

123
Q

What are the 4-ish phases of growth for finite cell lines?

A

Phase 1 - cells are adapting to culture, relatively slow growth
Phase 2 - cells are growing at doubling rate (~18-24h)
Crisis point - cells recognize own limited ability for cell division, growth slows
Phase 3 - growth slows further and eventually stops

124
Q

Define anchorage-dependence

A

need for solid substrate to grow

125
Q

Define density inhibition

A

maximum cell density, exhaustion of nutrients, complete cover of available growth surface

126
Q

Defined transformed cells

A

cells that are treated with a mutagenic agent such as UV rays, virus, oncogenes or can arise spontaneously

127
Q

When transformed cells acquire a capacity for infinite growth, what are they called?

A

established or continuous

128
Q

What are the differences between carcinogenesis in vivo to transformation of cell in vitro?

A
  • transformed cells are not necessarily malignant
  • malignant transformation likely requires several mutations
  • non-maligamt transformation requires a single mutation
129
Q

Define genomic ploidy

A

the number of copies of each chromosome in a cell

130
Q

What is the diploid chromosome number in normal human mammalian cells?

131
Q

What are the 4 other properties of normal mammalian cells?

A
  • anchorage dependence
  • a finite lifespan
  • nonmalignant (non-cancerous)
  • density inhibition
132
Q

What are the 3 characteristics and genomic policy in transformed mammalian cells (like CHO-K1)?

A
  • polyploid (more than 2 copies/chromosome) and can be aneuploid (fragmented chromosome)
  • infinite growth potential
  • loss of anchorage dependence
133
Q

What could explain some of the differences in performance of the mammalian cell lines in bioreactors?

A

there is evidence from whole genome analysis of different (clonal) CHO cell lines that there is clone-to-clone variability and aneuploidy

134
Q

What did Howard Cooke observe about human germline chromosomes?

A

the caps at the end of them were longer than those found in somatic cells

135
Q

What happens to human germline chromosomes with each generation of growth?

A

shortened (100 bases for human telomeres)

136
Q

Define telomerase

A

telomerase reverse transcriptase (TERT) + telomerase RNA (TERC)

137
Q

Who discovered telomerase?

A

Carol Greider & Elizabeth Blackburn

138
Q

What is the purpose of telomeres?

A

protects the chromosomes from degradation

139
Q

What is the function of telomerase?

A

builds telomere DNA (why transformed cells can keep growing)

140
Q

Does bacterial DNA have telomeres?

A

no, because their chromosome is a closed circular loop (DNA)

141
Q

Why does mammalian DNA need telomere caps?

A

because it is linear and susceptible to degradation

142
Q

In a hybridoma cell line, is the hayflick limit still observed?

143
Q

Borrellia and Streptomyces are bacteria with linear DNA, do they have telomeres? If not, what do they have instead?

A
  • Borrelia - linear ends closed with hairpin loops

- Streptomyces - proteins attached to ends of linear strands (act as primer for DNA synthesis)

144
Q

Define suspended growth

A

cells are freely dispersed in the growth medium and interact as a single or flocculated units

145
Q

Define supported growth

A

cells develop as a biofilm, normally on an inert support material and result in the formation of a complex interacting community of cells

146
Q

Define organ culture

A

slice tissue and displace at gas-liquid interface, usually passes through tissue and retains structural integrity

147
Q

Define explant culture

A

tissue is at solid-liquid interface, the whole tissue organs are transplanted from fetus and planted ex-vivo

148
Q

Define dissociated cell culture

A

tissue is separated into individual cells then grown onto 3D subs strip use disaggregated tissue

149
Q

Define organotypic culture

A

culture of an organ collected from an organism that allows to analyze complex tissue organs and preservation of the cultured organ and structure

150
Q

What are the 2 types of single-use shake flasks?

A
  • with or without baffles

- no baffles for mammalian cells?

151
Q

Define OUR

A

oxygen uptake rate

152
Q

What are the uses/advantages of single-use (disposable) microbioreactor systems? (5 things)

A
  • process development with process conditions approximating he manufacturing scale (results scalable to larger bench-scale + manufacturing bioreactors)
  • rapid tool for evaluating rate fo conditions and cell line/strain performance
  • process robustness studies (what limits of process are and setting working parameter ranges)
  • high culture development, more precise
  • no clean up post experimentation
153
Q

What are the 2 disadvantages of single-use (disposable) microbioreactor system?

A
  • more costly than shake flasks

- lots of training to operate and program runs

154
Q

What are the advantages to single-use bioreactors? (10 things)

A
  • reduces cleaning and sterilization needs
  • plant set up, space and operational cost are lower than classic fixed ones (~60% savings)
  • smaller footprint, less utilities/piping, can be changed quickly
  • reduces risk of cross-contamination = biological/process safety
  • cheaper & easier complex validation and quality control b/c no testing after each run
  • contain fewer parts than conventional bioreactor so initial/maintenance costs lower
  • flexibility in product output because of small max size so easy to add more bioreactors to increase production
  • technology transfer from ss bioreactors to SUBs easy because they perform similarly.
  • disposable sensors and probes
  • some suppliers can customize ports and sensor array
155
Q

What are the disadvantages of single-use bioreactors (SUBs)?

A
  • because small max size, best suited to high yield producing high value products
  • limiting factor is achievable oxygen transfer into solution, not suitable for bacterial processes (better for mammalian because oxygen transfer is lower)
  • cost of the disposable bag bioreactors is high & quality concerns require testing
  • generate lots of plastic wastes (environmental concern)
156
Q

What are the disadvantages of single-use bioreactors (SUBs)?

A
  • because small max size, best suited to high yield producing high value products
  • limiting factor is achievable oxygen transfer into solution, not suitable for bacterial processes (better for mammalian because oxygen transfer is lower)
  • cost of the disposable bag bioreactors is high & quality concerns require testing
  • generate lots of plastic wastes (environmental concern)
157
Q

What is the advantage of roller bottles?

A

changing process guest by varying number of bottles

158
Q

What is the disadvantages of roller bottles? (2 things)

A
  • difficult to precisely control parameters

- cant match yield and precise control of stirred tanks

159
Q

What is a disadvantage to cell factories?

A

difficult to monitor

160
Q

Define batch

A

closed system with a definite beginning and end

161
Q

Define fed-batch

A

closed system with extra nutrients added (continuously, intermittently, single)

162
Q

Define continuous

A

open system where fresh medium is added while culture simultaneously is removed and the system is in a steady state (concentrations nutrients and cell number do not say)

163
Q

What are 2 advantages of batch?

A
  • initial low cost to operate

- simple to implement and run

164
Q

What are disadvantages of batch? (6)

A
  • least effective for producing biomass
  • least Volumetric productivity
  • less control of bi-products (affect product yield and quality)
  • high non-productive downtime (eg. cleaning)
  • increased frequency of sterilization wears out instruments & probes
  • running costs high because each batch requires a culture seed train prior to the production bioreactor
165
Q

Batch product examples

A
  • amino acids
  • enzymes
  • organic acids
  • antibiotics
166
Q

What are the 4 advantages of fed-batch?

A
  • high cell density
  • highest volumetric production (g/L)
  • more control of bi-products which affect product yield and quality
  • regulatory acceptance highest, because much precedent in approved products
167
Q

What are the disadvantages of fed-batch? (6 things)

A

-optimal medium for production ≠ optimal for growth (increases prep complexity)
-though controlled better than batch, bi-products still impact the process
-high non-productive downtime (eg. cleaning)
-increased frequency of sterilization
wears out instruments & probes
-running costs high because each batch requires a culture seed train prior to the production Bioreactor
-more complex to run & control than batch

168
Q

Fed-batch product examples

A
  • alcoholic beverages
  • most amino acids
  • enzymes
  • organic acids
  • antibiotics
  • recombinant proteins
  • vaccines
169
Q

What are the 6 advantages of continuous/perfusion?

A
  • one medium for production & growth (no feeds), simpler
  • high cell density
  • highest specific productivity (g/L/day)
  • best control of bi-products which affect product yield and quality
  • reduced down-time
  • low running costs
170
Q

What are disadvantages of continuous/perfusion? (6 things)

A

-high initial investment
-sterility must be maintained through 20-50 days or more ( a lost run more costly than Batch or Fed-batch)
-larger tanks to store a supply of medium for continuous feeding
-long runs increase risk of low-yielding mutants developing in the culture
More technically demanding than fed-batch
-low volumetric production (g/L), makes downstream processing more difficult

171
Q

Continuous/perfusion product examples

A
  • biofuels
  • biomass
  • recombinant proteins
  • vaccines
172
Q

What are some controlled/measured physical parameters during industrial cell culture/fermentation? (5 things)

A
  • temperature (electrode)
  • airflow (meter)
  • agitation/speed of agitation (meter)
  • pressure (transducer)
  • liquid flow (transducer)
173
Q

What are some controlled/measured chemical parameters during industrial cell culture/fermentation? (8 things)

A
  • dissolved O2 (electrode)
  • dissolves CO2 (electrode)
  • nutrients eg. glucose (electrodes)
  • pH (electrode)
  • metal ions (electrode)
  • foam level/detection (electrode)
  • acid/alkali addition (meter)
  • on-line or off-line nutrient inflow and exhaust gas (mass spectra)
174
Q

What are some controlled/measured biological parameters during industrial cell culture/fermentation? (3 things)

A
  • biosensors for biologically active products (electrodes)
  • products (mass spec)
  • biomass (spectrophotometers - on-line and off-line)
175
Q

Define in-line measurements

A

sensor directly attached

176
Q

Define on-line measurements

A

take samples and recirculate in spectrometer

177
Q

Define at-line measurements

A

take samples out and take to instrument in proximity

178
Q

Define off-line measurement

A

taken to an instrument at a different lab bench (not close)

179
Q

What are the 4 alternate strategies for controlling dissolved oxygen?

A
  • change in air flow
  • intermittent oxygen sparging
  • control of gas composition
  • spin filter isolates cells from sparged gas
180
Q

How is the change in air flow rate a strategy for controlling dissolved oxygen?

A

filters bring in air which changes the concentration of dissolved O2

181
Q

Define PID

A

proportional-integral-derivative controller