A foreign body response-on-a-chip platform

Understanding the foreign body response (FBR) and desiging strategies to modulate such a response represent a grand challenge for implant devices and biomaterials. Here, the development of a microfluidic platform is reported, i.e., the FBR?on?a?chip (FBROC) for modeling the cascade of events during immune cell response to implants. The platform models the native implant microenvironment where the implants are interfaced directly with surrounding tissues, as well as vasculature with circulating immune cells. The study demonstrates that the release of cytokines such as monocyte chemoattractant protein 1 (MCP?1) from the extracellular matrix (ECM)?like hydrogels in the bottom tissue chamber induces trans?endothelial migration of circulating monocytes in the vascular channel toward the hydrogels, thus mimicking implant?induced inflammation. Data using patient?derived peripheral blood mononuclear cells further reveal inter?patient differences in FBR, highlighting the potential of this platform for monitoring FBR in a personalized manner. The prototype FBROC platform provides an enabling strategy to interrogate FBR on various implants, including biomaterials and engineered tissue constructs, in a physiologically relevant and individual?specific manner

Hybrid Microscopy: Enabling Inexpensive High-Performance Imaging through Combined Physical and Optical Magnifications

To date, much effort has been expended on making high-performance microscopes through better instrumentation. Recently, it was discovered that physical magnification of specimens was possible, through a technique called expansion microscopy (ExM), raising the question of whether physical magnification, coupled to inexpensive optics, could together match the performance of high-end optical equipment, at a tiny fraction of the price. Here we show that such “hybrid microscopy” methods—combining physical and optical magnifications—can indeed achieve high performance at low cost. By physically magnifying objects, then imaging them on cheap miniature fluorescence microscopes (“mini-microscopes”), it is possible to image at a resolution comparable to that previously attainable only with benchtop microscopes that present costs orders of magnitude higher. We believe that this unprecedented hybrid technology that combines expansion microscopy, based on physical magnification, and mini-microscopy, relying on conventional optics—a process we refer to as Expansion Mini-Microscopy (ExMM)—is a highly promising alternative method for performing cost-effective, high-resolution imaging of biological samples. With further advancement of the technology, we believe that ExMM will find widespread applications for high-resolution imaging particularly in research and healthcare scenarios in undeveloped countries or remote places

Hermetic glass -silicon micropackages and feedthroughs for neural prostheses.

This work describes extensive characterization and lifetime evaluation of a miniature hermetic glass-silicon packaging technology for implantable microsystem encapsulation. The package measures 2.3mm x 2.3mm x 10mm and is made to replace the titanium hermetic seals for chronic (> 40 years) applications. The packaging technology offers integrated high density feedthroughs (200/mm) to be utilized for lead transfer outside the package. Accelerated life tests have been developed and conducted to estimate lifetime at body temperature (37°C). Applying an Arrhenius model to the accelerated results in saline, an activation energy of 1.26 eV is calculated and a lifetime of 177 years is estimated at body temperature in saline. Tests in de-ionized water at 85°C that lasted close to 4 years demonstrate that, ignoring corrosion at the elevated temperatures, the glass-silicon package stays hermetic for > 164 years. Accelerated testing at high temperatures indicate that the corrosion problem, which does not occur at body temperature, needs to be addressed; hence, various measures including galvanic bias and heavy boron doping have been applied to the polysilicon layer which demonstrated satisfactory prevention of dissolution. The package can withstand tensile forces of up to 13 MPa. Alternate packaging technologies like (a) Au-Si eutectic and (b) evaporated glass assisted anodic sealing have been demonstrated as feasible means to be integrated into the microstimulator fabrication technology. The biocompatibility of the glass-silicon packages has been evaluated in various tissue samples and in different animal hosts which include guinea pigs (dura and abdomen), cats (bladder wall), and canines and rats (dorsum), up to a year. Histological evaluation of the tissue adjacent to implanted packages have shown no sign of infection, inflammation or tissue abnormality. The packages remained intact and hermetic during the course of the implants. A high-sensitivity ultra-thin film polyimide-based capacitive humidity sensor has also been developed to monitor internal humidity levels in anodically-bonded hermetic micropackages. This sensor is 1 mm on a side and utilizes CU1512 polyimide film with a thickness in the range of 300--1200A. The measured sensitivity for a sensor with a 1200A-thick film is 0.86pF/%RH and for a 300A-thick film is 3.4pF/%RH.Ph.D.Applied SciencesBiomedical engineeringElectrical engineeringPackagingUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/132334/2/9963768.pd

From cardiac tissue engineering to heart-on-a-chip: beating challenges

The heart is one of the most vital organs in the human body, which actively pumps the blood through the vascular network to supply nutrients to as well as to extract wastes from all other organs, maintaining the homeostasis of the biological system. Over the past few decades, tremendous efforts have been exerted in engineering functional cardiac tissues for heart regeneration via biomimetic approaches. More recently, progress has been made toward the transformation of knowledge obtained from cardiac tissue engineering to building physiologically relevant microfluidic human heart models (i.e. heart-on-chips) for applications in drug discovery. The advancement in stem cell technologies further provides the opportunity to create personalized in vitro models from cells derived from patients. Here, starting from heart biology, we review recent advances in engineering cardiac tissues and heart-on-a-chip platforms for their use in heart regeneration and cardiotoxic/cardiotherapeutic drug screening, and then briefly conclude with characterization techniques and personalization potential of the cardiac models

Harnessing the wide-range strain sensitivity of bilayered PEDOT:PSS films for wearable health monitoring

Mechanical deformation of human skin provides essential information about human motions, muscle stretching, vocal fold vibration, and heart rates. Monitoring these activities requires the measurement of strains at different levels. Herein, we report a wearable wide-range strain sensor based on conducting polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS). A bioinspired bilayer structure was constructed to enable a wide-range strain sensing (1%~100%). Besides, hydrogel was chosen as the biological- and mechanical-compatible interface layer with the human skin. Finally, we demonstrated that the strain sensor is capable of monitoring various strain-related activities, including subtle skin deformation (pulse and phonation), mid-level body stretch (swallowing and facial expressions), and substantial joint movement (elbow bending)

Automated microfluidic platform of bead-based electrochemical immunosensor integrated with bioreactor for continual monitoring of cell secreted biomarkers

There is an increasing interest in developing microfluidic bioreactors and organs-on-a-chip platforms combined with sensing capabilities for continual monitoring of cell-secreted biomarkers. Conventional approaches such as ELISA and mass spectroscopy cannot satisfy the needs of continual monitoring as they are labor-intensive and not easily integrable with low-volume bioreactors. This paper reports on the development of an automated microfluidic bead-based electrochemical immunosensor for in-line measurement of cell-secreted biomarkers. For the operation of the multi-use immunosensor, disposable magnetic microbeads were used to immobilize biomarker-recognition molecules. Microvalves were further integrated in the microfluidic immunosensor chip to achieve programmable operations of the immunoassay including bead loading and unloading, binding, washing, and electrochemical sensing. The platform allowed convenient integration of the immunosensor with liver-on-chips to carry out continual quantification of biomarkers secreted from hepatocytes. Transferrin and albumin productions were monitored during a 5-day hepatotoxicity assessment in which human primary hepatocytes cultured in the bioreactor were treated with acetaminophen. Taken together, our unique microfluidic immunosensor provides a new platform for in-line detection of biomarkers in low volumes and long-term in vitro assessments of cellular functions in microfluidic bioreactors and organs-on-chips

Automated microfluidic platform of bead-based electrochemical immunosensor integrated with bioreactor for continual monitoring of cell secreted biomarkers.

There is an increasing interest in developing microfluidic bioreactors and organs-on-a-chip platforms combined with sensing capabilities for continual monitoring of cell-secreted biomarkers. Conventional approaches such as ELISA and mass spectroscopy cannot satisfy the needs of continual monitoring as they are labor-intensive and not easily integrable with low-volume bioreactors. This paper reports on the development of an automated microfluidic bead-based electrochemical immunosensor for in-line measurement of cell-secreted biomarkers. For the operation of the multi-use immunosensor, disposable magnetic microbeads were used to immobilize biomarker-recognition molecules. Microvalves were further integrated in the microfluidic immunosensor chip to achieve programmable operations of the immunoassay including bead loading and unloading, binding, washing, and electrochemical sensing. The platform allowed convenient integration of the immunosensor with liver-on-chips to carry out continual quantification of biomarkers secreted from hepatocytes. Transferrin and albumin productions were monitored during a 5-day hepatotoxicity assessment in which human primary hepatocytes cultured in the bioreactor were treated with acetaminophen. Taken together, our unique microfluidic immunosensor provides a new platform for in-line detection of biomarkers in low volumes and long-term in vitro assessments of cellular functions in microfluidic bioreactors and organs-on-chips

Hydrophobic hydrogels: towards construction of floating (Bio) microdevices

Hydrogels, formed through crosslinking of hydrophilic polymer chains, represent a class of materials that are capable of holding large volumes of water. Here we report a novel class of hydrophobic hydrogels that can free-float on the surface of different aqueous media by coating conventional hydrogels with a layer of hydrophobic microparticles. We further demonstrate that these floating hydrogel-based devices can be used for sensing applications on liquid surfaces such as the construction of floating pH meters. Moreover, we demonstrate that the floating hydrogels present high mobility with excellent self-assembling property on the surface of water. Importantly, the floating systems reserved the intrinsic biocompatibility of the core hydrogels, enabling microengineering of floating tissue constructs. It is expected that these floating hydrophobic hydrogel-based devices will likely find widespread applications including but not limited to sensing, tissue engineering, and biomedicine.The authors acknowledge funding from the Office of Naval Research Young National Investigator Award, the National Institutes of Health (EB012597, AR057837, DE021468, HL099073, R56AI105024), and the Presidential Early Career Award for Scientists and Engineers (PECASE). N. M. Oliveira acknowledge the financial support from Portuguese Foundation for Science and Technology – FCT (Grant SFRH/BD/73172/2010), from the financial program POPH/FSE from QREN