Multilayer co-fired ceramic (MLCC) material systems and fabrication methods allow the easy fabrication of three dimensional features and integration of microfluidic channels and cavities into monolithic ceramic modules. In this work, an alumina based multilayer co-fired ceramic formulation and sintering methods suitable for producing transparent ceramic microfluidic modules is developed. Alumina slurries with high solid loading were prepared using an aqueous Duramax™ B-1000 binder systems. The rheological properties and casting behavior were studied for slurries with varying the binder additions. Sintering behavior of the green tapes were studied as well. Fundamental results indicated that the transparency of the ceramic with density over 3.98g/cm3 can be greatly improved after long time sintering at 1612°C in the H2. Finally, a microfluidic MLCC module with transparent window was demonstrated by patterning, laminating, and sintering the developed Al2O3 green tapes.

Low temperature co-fired ceramic (LTCC) electronic packaging materials are applied for the advantages of their mechanical durability, low cost, flexibility of the layered manufacturing, and capability to integrate both electronic and microfluidic functions in a single LTCC module. Clark-type oxygen sensors are electrochemical devices that are widely used for sensing dissolved oxygen in biological applications. In this paper, a Clark-type oxygen sensor has been developed using the LTCC thick-film technique instead of the traditional silicone/glass micromachining, and it consisted of an LTCC substrate with three electrodes (working electrode, counter electrode, and Ag/AgCl reference electrode), a polydimethylsiloxane (PDMS) oxygen permeable membrane and a PDMS reservoir. The fabricated Ag/AgCl reference electrode demonstrated high density with longtime stability. Cyclic voltammetry and chronoamperometry were measured to evaluate the electrochemical properties of the LTCC-based Clark-type oxygen sensor. The reduction current had a linear relationship with oxygen concentration. Meanwhile, the LTCC-based Clark-type oxygen sensor exhibited comparative performances, including low residual current, <;5%, and fast response time, 7.5 s, compared with the literatures.

A low temperature co-fired ceramic (LTCC) has been formulated and evaluated for in-vitro microfluidic sensors and cell culture applications. Using a 75/25 vol% glass to alumina ratio, high density was achieved for sintering temperatures <900 degrees C. No toxicity was observed in the leachate medium obtained by soaking LTCC in cell medium for 5 days. The human umbilical vein endothelial cells (HUVECs) also attached on the fibronectin-coated LTCC after 14hours and proliferated after 74hours. On the basis of these results, the current LTCC formulation is a viable candidate for the continued development of LTCC-based microfluidic biosensors.

Materials selection and evaluation is an integral aspect of the Engineering Design Process and an essential skill for the practicing engineer. Materials and their associated processing and forming methods serve to both enable and limit product design and performance. The current work presents the use of guided case studies as an approach to achieve a design-centric laboratory experience. The developed case study employed in the current investigation is the selection of sustainable materials for single use beverage containers. The learning outcomes of this approach were evaluated by surveys administered to two different groups of students: one group participating in the case study (intervention) and other participating in the pre-existing materials processing laboratory investigations (control) at two matched time points during the same semester. The initial self-assessment was administered before the three week case study intervention and the second survey was administered after the conclusion of the three week case study. Statistical analyses of survey results reveal significant difference between the two groups, in that students in the case study (intervention) group reported significant new learning in their ability to “design a materials specification” between the initial and final time points.

Low temperature co‐fired ceramics (LTCC) are widely utilized in the fabrication of compact, three dimensional, and highly integrated microelectronic components. Typical applications include military and mobile electronics applications requiring custom, hermetic, and/or high reliability packaging. These characteristics make LTCC attractive for use in microfluidic and biomedical application. However, commercial LTCC systems are not designed for biomedical applications and have unknown cytocompatibility. In the current work, an LTCC tape has been developed starting with materials of known composition and biocompatibility, a commercially available lime silicate glass and alumina. Tapes achieve high density for sintering temperatures compatible with LTCC processing (850 < T < 1000°C). The LTCC also exhibits low dielectric constant (K = 9.3) and dielectric loss (tan d < 0.005). A commercial gold electrode paste has also been co‐fired with the LTCC, with no delamination, cracks nor camber observed. In vitro biocompatibility was subsequently evaluated using human umbilical vein endothelial cells (HUVECs). HUVECs are observed to attach and spread on fibronectin‐coated LTCC substrates, and also in the leachate obtained by soaking LTCC in cell medium for 7 days. These results establish that the developed LTCC material is biocompatible and suitable for in vitro applications utilizing live cells.

Trans-endothelial Electrical Resistance (TEER) and cellular impedance measurements are widely used to evaluate the barrier properties and functional change of endothelial cell monolayers. In the current work, low temperature cofired ceramics (LTCC) are applied enabling the incorporation of TEER and impediametric measurements in an integrated microfluidic chip. LTCC materials are an ideal substrate for biomedical and cell-based microfluidics due to their biocompatibility and ability to combine complex three dimensional structures with optical, fluidic, and electrical functionality. Multilayer microfluidic ceramic devices incorporating gold measurement electrodes where prepared using standard LTCC manufacturing procedures. The sensitivity of the resulting LTCC devices were compared to systems currently on the market for TEER measurements. These results indicate the LTCC device is able to effectively detect the growth of an endothelial cell monolayer. Results further evaluate endothelial cell viability using electrical resistance and Live/Dead assay. Finally, the results from this study also display improved sensitivity through the optimization of the electrode geometry and use of a lock-in amplifier. These results provide a solid basis for using low temperature co-fired ceramic materials for microfluidic TEER devices.

The biomedical use of superparamagnetic iron oxide nanoparticles has been of continued interest in the literature and clinic. Their ability to be used as contrast agents for imaging and/or responsive agents for remote actuation makes them exciting materials for a wide range of clinical applications. Recently, however, concern has arisen regarding the potential health effects of these particles. Iron oxide toxicity has been demonstrated in in vivo and in vitro models, with oxidative stress being implicated as playing a key role in this pathology. One of the key cell types implicated in this injury is the vascular endothelial cells. Here, we report on the development of a targeted polymeric antioxidant, poly(trolox ester), nanoparticle that can suppress oxidative damage. As the polymer undergoes enzymatic hydrolysis, active trolox is locally released, providing a long term protection against pro-oxidant agents. In this work, poly(trolox) nanoparticles are targeted to platelet endothelial cell adhesion molecules (PECAM-1), which are able to bind to and internalize in endothelial cells and provide localized protection against the cytotoxicity caused by iron oxide nanoparticles. These results indicate the potential of using poly(trolox ester) as a means of mitigating iron oxide toxicity, potentially expanding the clinical use and relevance of these exciting systems.

The expense and difficulty of current biomarker detection methods is driving the design of microfluidic detection platforms. A ceramic microfluidic biosensor has been developed for conducting enzyme-linked immunosorbent assays (ELISA) using a novel polymerization amplified thermal detection (PATD) scheme. Prototype testing has yielded several results that support the viability of this device. It was seen that LTCC is an effective and durable substrate for the temperature sensor. Noise testing with our prototype revealed that our temperature sensors can detect changes as small as 0.01 K. Additional temperature testing showed that the thermistor behavior matches the expected thermistor beta equation. Finally, it was shown that polymerization reaction induction time is inversely proportional to glucose oxidase (GOx) initiator concentration. These preliminary results provide a foundation for future work developing the sensor into a protein detection device with cancer prognosis applications.

Low temperature co-fired ceramic (LTCC) electronic packaging materials are applied for their ease of fabrication, three dimensional features and integration of multifunctional component, such as optical and electrical functions. For these reasons LTCC is attractive for biomedical microfluidics and Lab-on-a-Chip systems. However, commercial LTCC systems, optimized for microelectrics applications, are not designed for biomedical applications, and have unknown cytocompatibility. In the current work, LTCC has been developed starting with materials of known composition and biocompatibility. The developed LTCC, fabricated from a lime silicate glass and pure alumina, exhibits low sintering temperature (<1000°C) and high density. Alumina reacts with the glass and forms anorthite type crystalline phase CaAl2Si2O8 at temperature 900°C. A commercial gold electrode paste has also been co-fired with the LTCC, with no delamination, cracks nor camber observed. In-vitro biocompatibility of LTCC has been evaluated using human umbilical vein endothelial cells (HUVEC). The HUVECs attach and spread on the surface of the LTCC substrates, and also in the leachate obtained by soaking LTCC in cell media for seven days. The cell density and percentage of live cells on LTCC surface are comparative with those of control. Results indicate the developed LTCC materials are biocompatible and suitable for biomedical applications.

A package-level peristaltic piezoelectric micropump has been designed and fabricated in utilizing multilayer ceramic fabrication methods. The device was fabricated using commercially available low-temperature cofired ceramic materials and a custom-designed low-temperature cofired ceramic compatible piezoelectric ceramic composition. The assembled multilayer pump structure was sintered in single cofiring step. Performance testing resulted in observed unloaded bidirectional flow rates of 450 µL/min and a blocking pressure of 1.4 kPa when the pump was operated at a voltage of 100 Vpp (with a phase difference of 120°) with a frequency of 100 Hz. It was further shown that incorporation of diffuser elements into the microfluidic interconnects was used to increase the blocking pressure capabilities at the expense of flow rate and bidirectional flow characteristics. Alternatively, by maintaining a uniform channel width but varying channel cross section width over height ratio (W/H), an unloaded flow rate of 630 µL/min with an enhancement of blocking pressure (1.55 kPa) was achieved for W/H = 3 (and the same drive conditions as above). The resulting multilayer ceramic-based piezoelectric micropump offers a compact planar pump design, with significant performance advantages, and design flexibility compared to competing micropump technologies.

Expansion of Low-Temperature Co-fired Ceramic materials into microfluidic systems technology has many beneficial applications due to their ability to combine complex three dimensional structures with optical, fluidic, electrical functions. Evaluations of the biocompatibility of these Low-Temperature Co-fired Ceramic materials are vital for expanding into biomedical research. The few biocompatibility studies on Low-Temperature Co-fired Ceramics generally show negative cellular response to thick film pastes used in generating the electronic circuitry patterns. In this study, biocompatibility of Human Umbilical Vein Endothelial Cells was examined on Heraeus's Low-Temperature Co-fired Ceramic tape and two of their conductive pastes. The biocompatibility was assessed by monitoring cellular attachment and viability up to three days. This study examines the idea of leachates being detrimental to cells due to a study that suggests the possibility of harmful leachates. Results indicate difficulty in initial attachment of Human Umbilical Vein Endothelial Cells to sintered Low-Temperature Co-fired Ceramic tapes, but no hindrance of cellular attachment and growth onto the two conductive pastes. Outcomes also demonstrate that possible harmful leachates from Low-Temperature Co-fired Ceramic materials don't thwart cellular attachment and growth for up to three days of cell culturing. These results provide a basis for biological devices using Low-Temperature Co-fired Ceramic materials.

Materials and processing conditions have been developed allowing co‐firing of fluxed PZT‐SKN materials with commercial low temperature co‐fired ceramic (LTCC) tapes. Previously, Pb(Zr0.53, Ti0.47)O3–Sr(K0.25, Nb0.75)O3 (PZT‐SKN) ceramics fluxed with 1 wt% LiBiO2 and 1 wt% CuO addition were shown to sinter to high density at 900°C for 1 h, with a large d33 piezoelectric coefficient of ~415 pm/V. Currently, the master sintering curve (MSC) approach has been used to study the densification behaviors of fluxed PZT‐SKN and LTCC tapes. Different sintering mechanisms for fluxed PZT‐SKN ceramics and LTCC materials are confirmed by analyzing the apparent activation energy (Qa). Using knowledge gained from MSC results, an optimized sintering profile was developed. Multilayer PZT‐SKN/HL2000 (HeraLock™ Tape, Heraeus) stacks co‐fired at 900°C for 0.5 h maintain large piezoelectric coefficient (high field d33 > 340 pm/V). EDS analysis reveal limited interdiffusion of Pb from PZT‐SKN layers in LTCC and the appearance of Al, Ca, and Si in the PZT‐SKN near the PZT‐SKN/LTCC interface. Further, elemental interdiffusion was not detected at the center of piezoelectric layer in PZT‐SKN/LTCC multilayer ceramics and no subsequent reduction in piezoelectric coefficient d33 was observed. Finally, a piezoelectric microbalance with mass sensitivity of 150 kHz/mg was fabricated using the materials and methods developed.

Attenuation of cellular oxidative stress, which plays a central role in biomaterial-induced inflammation, provides an exciting opportunity to control the host tissue response to biomaterials. In the case of biodegradable polymers, biomaterial-induced inflammation is often a result of local accumulation of polymer degradation products, hence there is a need for new biomaterials that can inhibit this response. Antioxidant polymers, which have antioxidants incorporated into the polymer backbone, are a class of biomaterials that, upon degradation, release active antioxidants, which can scavenge free radicals and attenuate oxidative stress, resulting in improved material biocompatibility. In this work, we have synthesized poly(antioxidant β-amino ester) (PAβAE) biodegradable hydrogels of two polyphenolic antioxidants, quercetin and curcumin. The degradation characteristics of PAβAE hydrogels and the antioxidant activity of PAβAE degradation products were studied. Treatment of endothelial cells with PAβAE degradation products protected cells from hydrogen-peroxide-induced oxidative stress.

Integrated low‐temperature co‐fired ceramic (LTCC) modules are widely used in commercial wireless data and cellular communication devices. Recently, a number of researchers have demonstrated the use of LTCC materials and assembly processes to build integrated microelectromechanical and microfluidic devices, incorporating a variety of electrical, optical, electromechanical, and fluidic functions. However, the long‐term stability and biocompatibility of the LTCC materials for microfluidic and specifically biomedical devices have yet to be addressed. The biostability of LTCC materials has been examined in three different commercial LTCC materials using a bioleaching approach. The leaching rate has been obtained in several common biological fluids using weight loss and elemental analysis to quantify the leaching rate. Our results indicate significant dissolution of LTCC materials in simulated gastric fluid and highly basic solutions. However, only minimal leaching was demonstrated in both phosphate buffer saline and simulated body fluid solutions.

The low-temperature sintering behavior of Pb(Zr-0.53, Ti-0.47) O-3-Sr(K-0.25, Nb-0.75)O-3 (PZT-SKN) piezoelectric ceramics with LiBiO2 and CuO addition has been investigated. The addition of 6 wt% LiBiO2 or 1 wt% LiBiO2+1 wt% CuO promotes the sinterability of 0.98PZT-0.02SKN ceramics owing to the generation of a liquid phase, resulting in a reduction of sintering temperature by about 300 degrees-350 degrees C. The microstructure, dielectric, and piezoelectric properties of flux-sintered ceramics were examined and compared with materials conventionally sintered at 1250 degrees C. PZT-SKN ceramics with 1 wt% LiBiO2+1 wt% CuO addition were sintered to high density at 900 degrees C for 1 h. The resulting samples exhibited a high-field d(33) piezoelectric coefficient of 415 pm/V with a Curie temperature T-c of around 351 degrees C, dielectric constant epsilon(r) of 1235, and planar coupling factor k(p) of 0.54. The reduced sintering temperature and short soaking time, together with the favorable dielectric and piezoelectric properties of the fluxed PZT-SKN ceramics, demonstrate the potential opportunity of integration with low-temperature cofired ceramic materials and low-fire electrode materials for the multilayer piezoelectric transducer application.