Design and optimization of a novel patient-specific subperiosteal implant additively manufactured in yttria-stabilized zirconia.

OBJECTIVE: To design a patient-specific subperiosteal implant for a severely atrophic maxillary ridge using yttria-stabilized additively manufactured zirconia (3YSZ) and evaluate its material properties by applying topology optimization (TO) to replace bulk material with a lattice structure. MATERIALS: A contrast-based segmented skull model from anonymized computed tomography data of a patient was used for the initial anatomical design of the implant for the atrophic maxillary ridge. The implant underwent finite element analysis (FEA) and TO under different occlusal load-bearing conditions. The resulting implant designs, in bulk material and lattice, were evaluated via in-silico tensile tests and 3D printed. RESULTS: The workflow produced two patient-specific subperiosteal designs: a) an anatomically precise bulk implant, b) a TO lattice implant. In-silico tensile tests revealed that the Young's modulus of yttria-stabilized zirconia is 205 GPa for the bulk material and 83.3 GPa for the lattice. Maximum principal stresses in the implant were 61.14 MPa in bulk material and 278.63 MPa in lattice, both tolerable, indicating the redesigned implant can withstand occlusal forces of 125-250 N per abutment. Furthermore, TO achieved a 13.10 % mass reduction and 208.71 % increased surface area, suggesting improved osteointegration potential. SIGNIFICANCE: The study demonstrates the planning and optimization of ceramic implant topology. A further iteration of the implant was successfully implanted in a patient-named use case, employing the same fabrication process and parameters.

Continuous on-chip fluorescence labelling, free-flow isoelectric focusing and marker-free isoelectric point determination of proteins and peptides.

We present a microfluidic platform that contains a micro flow reactor for on-chip biomolecule labelling that is directly followed by a separation bed for continuous free-flow electrophoresis and has an integrated hydrogel-based near-infrared fluorescent pH sensor layer. Using this assembly, labelling of protein and peptide mixtures, their separation via free-flow isoelectric focusing and the determination of the isoelectric point (pI) of the separated products via the integrated sensor layer could be carried out within typically around 5 minutes. Spatially-resolved immobilization of fluidic and sensing structures was carried out via multistep photolithography. The assembly was characterized and optimized with respect to their fluidic and pH sensing properties and applied in the IEF of model proteins, peptides and a tryptic digest from physalaemine. We have therefore realized continuous sample preparation and preparative separation, analyte detection, process observation and analyte assignment capability based on pI on a single platform the size of a microscope slide.

Label-free microfluidic free-flow isoelectric focusing, pH gradient sensing and near real-time isoelectric point determination of biomolecules and blood plasma fractions.

We demonstrate the fabrication, characterization and application of microfluidic chips capable of continuous electrophoretic separation via free flow isoelectric focussing (FFIEF). By integration of a near-infrared (NIR) fluorescent pH sensor layer under the whole separation bed, on-line observation of the pH gradient and determination of biomolecular isoelectric points (pI) was achieved within a few seconds. Using an optical setup for imaging of the intrinsic fluorescence of biomolecules at 266 nm excitation, labelling steps could be avoided and the native biomolecules could be separated, collected and analysed for their pI. The fabricated microchip was successfully used for the monitoring of the separation and simultaneous observation of the pH gradient during the isoelectric focussing of the proteins α-lactalbumin and ß-lactoglobulin, blood plasma proteins and the antibiotics ampicillin and ofloxacin. The obtained pIs are in good agreement with literature data, demonstrating the applicability of the system. Mass spectra from the separated antibiotics taken after 15 minutes of continuous separation from different fractions at the end of the microchip validated the separation via microfluidic isoelectric focussing and indicate the possibility of further on- or off-chip processing steps.

Enhancing photoinduced electron transfer efficiency of fluorescent pH-probes with halogenated phenols.

Photoinduced electron transfer (PET), which causes pH-dependent quenching of fluorescent dyes, is more effectively introduced by phenolic groups than by amino groups which have been much more commonly used so far. That is demonstrated by fluorescence measurements involving several classes of fluorophores. Electrochemical measurements show that PET in several amino-modified dyes is thermodynamically favorable, even though it was not experimentally found, underlining the importance of kinetic aspects to the process. Consequently, the attachment of phenolic groups allows for fast and simple preparation of a wide selection of fluorescent pH-probes with tailor-made spectral properties, sensitive ranges, and individual advantages, so that a large number of applications can be realized. Fluorophores carrying phenolic groups may also be used for sensing analytes other than pH or molecular switching and signaling.

Fluorescent materials for pH sensing and imaging based on novel 1,4-diketopyrrolo-[3,4-c]pyrrole dyes†Electronic supplementary information (ESI) available: NMR and MS spectra, further sensor characteristics and sensor long-time performance. See DOI: 10.1039/c3tc31130aClick here for additional data file.

New optical pH-sensors relying on 1,4-diketopyrrolo-[3,4-c]pyrroles (DPPs) as fluorescent pH-indicators are presented. Different polymer hydrogels are useful as immobilization matrices, achieving excellent sensitivity and good brightness in the resulting sensor. The operational pH can be tuned over a wide range (pH 5-12) by selecting the fine structure of the indicator and the matrix. A ratiometric sensor in the form of nanoparticles is also presented. It is suitable for RGB camera readout, and its practical applicability for fluorescence imaging in microfluidic systems is demonstrated. The indicators are synthesized starting from the commercially available DPP pigments by a straightforward concept employing chlorosulfonation and subsequent reaction with amines. Their sensitivity derives from two distinct mechanisms. At high pH (>9), they exhibit a remarkable alteration of both absorption and fluorescence spectra due to deprotonation of the lactam nitrogen atoms. If a phenolic group is introduced, highly effective fluorescence quenching at near-neutral pH occurs due to photoinduced electron transfer (PET) involving the phenolate form.

Novel near infra-red fluorescent pH sensors based on 1-aminoperylene bisimides covalently grafted onto poly(acryloylmorpholine).

Novel pH sensors relying on 1-aminoperylene bisimide dyes covalently grafted onto cross-linked poly(acryloylmorpholine) are presented. They feature fluorescence in the near infra-red range and a large Stokes shift (>90 nm).

New fluorescent pH sensors based on covalently linkable PET rhodamines.

A new class of rhodamines for the application as indicator dyes in fluorescent pH sensors is presented. Their pH-sensitivity derives from photoinduced electron transfer between non-protonated amino groups and the excited chromophore which results in effective fluorescence quenching at increasing pH. The new indicator class carries a pentafluorophenyl group at the 9-position of the xanthene core where other rhodamines bear 2-carboxyphenyl substituents instead. The pentafluorophenyl group is used for covalent coupling to sensor matrices by "click" reaction with mercapto groups. Photophysical properties are similar to "classical" rhodamines carrying 2'-carboxy groups. pH sensors have been prepared with two different matrix materials, silica gel and poly(2-hydroxyethylmethacrylate). Both sensors show high luminescence brightness (absolute fluorescence quantum yield Φ(F)≈0.6) and high pH-sensitivity at pH 5-7 which makes them suitable for monitoring biotechnological samples. To underline practical applicability, a dually lifetime referenced sensor containing Cr(III)-doped Al(2)O(3) as reference material is presented.

New fluorescent perylene bisimide indicators--a platform for broadband pH optodes.

Asymmetric perylene bisimide (PBI) dyes are prepared and are shown to be suitable for the preparation of fluorescence chemosensors for pH. They carry one amino-functional substituent which introduces pH sensitivity via photoinduced electron transfer (PET) while the other one increases solubility. The luminescence quantum yields for the new indicators exceed 75% in the protonated form. The new indicators are non-covalently entrapped in polyurethane hydrogel D4 and poly(hydroxyalkylmethacrylates). Several PET functions including aliphatic and aromatic amino groups were successfully used to tune the dynamic range of the sensor. Because of their virtually identical spectral properties, various PBIs with selected PET functions can easily be integrated into a single sensor with enlarged dynamic range (over 4 pH units). PBIs with two different substitution patterns in the bay position are investigated and possess variable spectral properties. Compared with their tetrachloro analogues, tetra-tert-butyl-substituted PBIs yield more long-wave excitable sensors which feature excellent photostability. Cross-sensitivity to ionic strength was found to be negligible. The practical applicability of the sensors may be compromised by the long response times (especially in case of tetra-tert-butyl-substituted PBIs).