Danksagung ..................................................... IV
Summary ........................................................ IX
Zusammenfassung ................................................. X
List of Abbreviations .......................................... XI
List of Symbols ............................................... XLV
ьst of Cells ................................................... XV
Chapter 1: Introduction ......................................... 1
General introduction ......................................... 2
The single cell as the basic biological unit ................. 3
Single-cell analysis requires environmental control .......... 4
Physiological consequences of environmental gradients
and implications for microfluidic single-cell analysis ....... 7
The single-cell continuum ...................................... 10
Hydrodynamics shape the physical architecture of the
single-cell boundary environment ............................ 11
Microfluidic single-cell analysis enables
environmental control ....................................... 14
Single-cell cultivation in controlled environments with
the Envirostat ................................................. 16
The catalytic black box: How to assess single cells in
a biotechnological context? .................................... 20
Conclusions .................................................... 22
Scope of the thesis ............................................ 23
Chapter 2: Time-resolved single-cell analysis reveals
elevated specific growth rates of isolated microbes and
micropopulations in controlled environments .................... 25
Summary ........................................................ 26
Introduction ................................................... 27
Materials and Methods .......................................... 29
Results and Discussion ......................................... 34
Conclusions .................................................... 40
Chapter 3: Microfluidic control of single yeast
microenvironments discloses ultrasensitive of the mox
promoter to carbon catabolite repression ....................... 41
Summary ........................................................ 42
Introduction ................................................... 43
Materials and Methods .......................................... 46
Results ........................................................ 53
Discussion ..................................................... 68
Conclusions .................................................... 71
Chapter 4: Quantitative measurement of glucose uptake at
a single-cell level ............................................ 73
Summary ..................................................... 74
Introduction ................................................ 75
Materials and Methods ....................................... 79
Results ..................................................... 85
Discussion ................................................. 104
Conclusions ................................................ 108
Chapter 5: The flux probe concept - secreted protein as
a non-disruptive information carrier for I3C-based
metabolic flux analysis ....................................... 111
Summary ....................................................... 112
Introduction .................................................. 113
Materials and Methods ......................................... 116
Results ....................................................... 121
Discussion .................................................... 135
Conclusions ................................................... 138
Chapter 6: Technical bias of microcultivation
environments on single-cell physiology ........................ 139
Summary ....................................................... 140
Introduction .................................................. 141
Materials and Methods ......................................... 146
Results ....................................................... 149
Discussion .................................................... 157
Conclusions ................................................... 160
Chapter 7: General discussion ................................. 161
Introduction .................................................. 162
Beyond the bulk: Analytical concepts for single-cell
analysis ...................................................... 163
Pivotal descriptors for single-cell physiology: linking
cell and environment .......................................... 175
Conclusions ................................................... 188
Chapter 8: Concluding remarks and outlook ..................... 189
Challenging biological limits with microfluidic single-
cell analysis ................................................. 190
Outlook ....................................................... 193
Chapter 9: Appendix ........................................... 195
Chapter 10: References ........................................ 207
Curriculum vitae .............................................. 229
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