Ingestible Sensors and Sensing Systems for Minimally Invasive Diagnosis and Monitoring: The Next Frontier in Minimally Invasive Screening.

Ingestible electronic systems that are capable of embedded sensing, particularly within the gastrointestinal (GI) tract and its accessory organs, have the potential to screen for diseases that are difficult if not impossible to detect at an early stage using other means. Furthermore, these devices have the potential to (1) reduce labor and facility costs for a variety of procedures, (2) promote research for discovering new biomarker targets for associated pathologies, (3) promote the development of autonomous or semiautonomous diagnostic aids for consumers, and (4) provide a foundation for epithelially targeted therapeutic interventions. These technological advances have the potential to make disease surveillance and treatment far more effective for a variety of conditions, allowing patients to lead longer and more productive lives. This review will examine the conventional techniques, as well as ingestible sensors and sensing systems that are currently under development for use in disease screening and diagnosis for GI disorders. Design considerations, fabrication, and applications will be discussed.

A Modular, Reconfigurable Microfabricated Assembly Platform for Microfluidic Transport and Multitype Cell Culture and Drug Testing.

Modular microfluidics offer the opportunity to combine the precise fluid control, rapid sample processing, low sample and reagent volumes, and relatively lower cost of conventional microfluidics with the flexible reconfigurability needed to accommodate the requirements of target applications such as drug toxicity studies. However, combining the capabilities of fully adaptable modular microelectromechanical systems (MEMS) assembly with the simplicity of conventional microfluidic fabrication remains a challenge. A hybrid polydimethylsiloxane (PDMS)-molding/photolithographic process is demonstrated to rapidly fabricate LEGO®-like modular blocks. The blocks are created with different sizes that interlock via tongue-and-groove joints in the plane and stack via interference fits out of the plane. These miniature strong but reversible connections have a measured resistance to in-plane and out-of-plane forces of up to >6000× and >1000× the weight of the block itself, respectively. The LEGO®-like interference fits enable O-ring-free microfluidic connections that withstand internal fluid pressures of >120 kPa. A single layer of blocks is assembled into LEGO®-like cell culture plates, where the in vitro biocompatibility and drug toxicity to lung epithelial adenocarcinoma cells and hepatocellular carcinoma cells cultured in the modular microwells are measured. A double-layer block structure is then assembled so that a microchannel formed at the interface between layers connects two microwells. Breast tumor cells and hepatocytes cultured in the coupled wells demonstrate interwell migration as well as the simultaneous effects of a single drug on the two cell types.

Generation of Cost-Effective Paper-Based Tissue Models through Matrix-Assisted Sacrificial 3D Printing.

Due to the combined advantages of cellulose and nanoscale (diameter 20-60 nm), bacterial cellulose possesses a series of attractive features including its natural origin, moderate biosynthesis process, good biocompatibility, and cost-effectiveness. Moreover, bacterial cellulose nanofibers can be conveniently processed into three-dimensional (3D) intertwined structures and form stable paper devices after simple drying. These advantages make it suitable as the material for construction of organ-on-a-chip devices using matrix-assisted sacrificial 3D printing. We successfully fabricated various microchannel structures embedded in the bulk bacterial cellulose hydrogels and retained their integrity after the drying process. Interestingly, these paper-based devices containing hollow microchannels could be rehydrated and populated with relevant cells to form vascularized tissue models. As a proof-of-concept demonstration, we seeded human umbilical vein endothelial cells (HUVECs) into the microchannels to obtain the vasculature and inoculated the MCF-7 cells onto the surrounding matrix of the paper device to build a 3D paper-based vascularized breast tumor model. The results showed that the microchannels were perfusable, and both HUVECs and MCF-7 cells exhibited favorable proliferation behaviors. This study may provide a new strategy for constructing simple and low-cost in vitro tissue models, which may find potential applications in drug screening and personalized medicine.

Micro Motion Amplifiers for Compact Out-of-Plane Actuation.

Small-scale, out-of-plane actuators can enable tactile interfaces; however, achieving sufficient actuator force and displacement can require larger actuators. In this work, 2-mm² out-of-plane microactuators were created, and were demonstrated to output up to 6.3 µm of displacement and 16 mN of blocking force at 170 V. The actuators converted in-plane force and displacement from a piezoelectric extensional actuator into out-of-plane force and displacement using robust, microelectromechanical systems (MEMS)-enabled, half-scissor amplifiers. The microscissors employed two layers of lithographically patterned SU-8 epoxy microstructures, laminated with a thin film of structural polyimide and adhesive to form compact flexural hinges that enabled the actuators' small area. The self-aligned manufacture minimized assembly error and fabrication complexity. The scissor design dominated the actuators' performance, and the effects of varying scissor angle, flexure thickness, and adhesive type were characterized to optimize the actuators' output. Reducing the microscissor angle yielded the highest actuator performance, as it maximized the amplification of the half-scissor's displacement and minimized scissor deformation under externally applied loads. The actuators' simultaneously large displacements and blocking forces for their size were quantified by a high displacement-blocking force product per unit area of up to 50 mN·µm/mm². For a linear force⁻displacement relationship, this corresponds to a work done per unit area of 25 mN·µm/mm².