104
A. S. Cerda-Kipper and S. Hosseini
signal was a function of the shelf life of the luminescence sensor spots. This shift
in the angle of luminescence was utilized as the measurement signal. For observing
enzymatic responses on the microscale, this method offered great potential without
needing complicated instruments except for a fluorescence microscope. The fabrication of sensor structures from several prepolymer combinations was found possible.
The microsensors were analyzed and have shown good sensitivity in detection and
reasonable stability. Such integration methods may influence future development of
flow reactors and have an impact on miniaturized cell culture and organ and tissue
on a chip fields of knowledge (Pfeiffer et al. 2017).
4.4 Alternative BioMEMS for Luminescence Detection
In biomedicine, an important biomarker for inflammation is hydrogen peroxide
(H 2 O 2 ), and its quantification is important in assays engaging enzymes that produce
or consume H 2 O 2 linked to a particular biomarker (Pratsinis 2017). However, the
optical detection of H 2 O 2 has been commonly performed via peroxidase-coupled
reactions using organic dyes. Due to its weak stability and/or reproducibility, this
method cannot be used in-situ in multifunctional and complicated cell cultures that
aim at detecting H 2 O 2 levels in real-time. Henning et al. used enzyme-mimetic
CeO 2 nanocrystals that are sensitive to H 2 O 2 and studied the impact of H 2 O 2 on
electronic and luminescent nature of these nanocrystals. The authors demonstrated
the performance of the biosensors by observing and recording their responses to a
wide range of H 2 O 2 concentrations from S. pneumoniae, and consequently highlighted the potential of these biosensing platforms for real-time H 2 O 2 monitoring
in-vitro within cell culture systems (Henning 2019). The authors investigated the
usefulness of flame nanoparticle synthesis for the development of a ratiometric
H 2 O 2 biosensor based upon a double-nozzle flame spray pyrolysis of multicomponent nanoparticles performed in one step and previously developed by Strobel
(2006). For nanomanufacturing processes, double-nozzle flame synthesis produced
multicomponent nanoparticle systems with careful control over the size of the products and morphology independent of each nozzle. This process allowed individual
control over particle growth in the intersection of each flame (Grossmann et al. 2015).
However, the authors extended its use for the production of bio-responsive materials
and explored the synthesis of enzyme-mimetic luminescent and H 2 O 2 -responsive
CeO 2 : Eu
3+ nanoparticles mixed with larger luminescent nonresponsive Y 2 O 3 :Tb
3+
nanoparticles (Büchel et al. 2009). To assure that the nanoparticles were mixed in the
nanoscale and did not create solid componets or mixed crystal phases, the authors
adjusted the two nozzles angles at 60°, in the double-nozzle setup (Fig. 4.1). Likewise,
in-situ flame annealing was used to enhance the structural stability since it allows the
porous nanoparticle films to be dipped into liquids without restructuring or loosing
particle film. The main advantage of the newly developed method over the single
nozzle synthesis, was that the hybrid nanoaggregates are made in a one step process
minimizing the production time to half. Importantly, all constituents were present
A. S. Cerda-Kipper and S. Hosseini
signal was a function of the shelf life of the luminescence sensor spots. This shift
in the angle of luminescence was utilized as the measurement signal. For observing
enzymatic responses on the microscale, this method offered great potential without
needing complicated instruments except for a fluorescence microscope. The fabrication of sensor structures from several prepolymer combinations was found possible.
The microsensors were analyzed and have shown good sensitivity in detection and
reasonable stability. Such integration methods may influence future development of
flow reactors and have an impact on miniaturized cell culture and organ and tissue
on a chip fields of knowledge (Pfeiffer et al. 2017).
4.4 Alternative BioMEMS for Luminescence Detection
In biomedicine, an important biomarker for inflammation is hydrogen peroxide
(H 2 O 2 ), and its quantification is important in assays engaging enzymes that produce
or consume H 2 O 2 linked to a particular biomarker (Pratsinis 2017). However, the
optical detection of H 2 O 2 has been commonly performed via peroxidase-coupled
reactions using organic dyes. Due to its weak stability and/or reproducibility, this
method cannot be used in-situ in multifunctional and complicated cell cultures that
aim at detecting H 2 O 2 levels in real-time. Henning et al. used enzyme-mimetic
CeO 2 nanocrystals that are sensitive to H 2 O 2 and studied the impact of H 2 O 2 on
electronic and luminescent nature of these nanocrystals. The authors demonstrated
the performance of the biosensors by observing and recording their responses to a
wide range of H 2 O 2 concentrations from S. pneumoniae, and consequently highlighted the potential of these biosensing platforms for real-time H 2 O 2 monitoring
in-vitro within cell culture systems (Henning 2019). The authors investigated the
usefulness of flame nanoparticle synthesis for the development of a ratiometric
H 2 O 2 biosensor based upon a double-nozzle flame spray pyrolysis of multicomponent nanoparticles performed in one step and previously developed by Strobel
(2006). For nanomanufacturing processes, double-nozzle flame synthesis produced
multicomponent nanoparticle systems with careful control over the size of the products and morphology independent of each nozzle. This process allowed individual
control over particle growth in the intersection of each flame (Grossmann et al. 2015).
However, the authors extended its use for the production of bio-responsive materials
and explored the synthesis of enzyme-mimetic luminescent and H 2 O 2 -responsive
CeO 2 : Eu
3+ nanoparticles mixed with larger luminescent nonresponsive Y 2 O 3 :Tb
3+
nanoparticles (Büchel et al. 2009). To assure that the nanoparticles were mixed in the
nanoscale and did not create solid componets or mixed crystal phases, the authors
adjusted the two nozzles angles at 60°, in the double-nozzle setup (Fig. 4.1). Likewise,
in-situ flame annealing was used to enhance the structural stability since it allows the
porous nanoparticle films to be dipped into liquids without restructuring or loosing
particle film. The main advantage of the newly developed method over the single
nozzle synthesis, was that the hybrid nanoaggregates are made in a one step process
minimizing the production time to half. Importantly, all constituents were present
