3D printing involves the use of toxic photopolymerizable resins which typically have incompatible properties with polystyrene for biomedical applications. Herein, we use 3D printing tricks and polydopamine to dramatically improve adhesion.
Benchtop tissue cultures have become increasingly complex in recent years, as more on-a-chip biological technologies, such as microphysiological systems (MPS), are developed to incorporate cellular constructs that more accurately represent their respective biological systems. Such MPS have begun facilitating major breakthroughs in biological research and are poised to shape the field in the coming decades. These biological systems require integrated sensing modalities to procure complex, multiplexed datasets with unprecedented combinatorial biological detail. In this work, we expanded upon our polymer-metal biosensor approach by demonstrating a facile technology for compound biosensing that was characterized through custom modeling approaches. As reported herein, we developed a compound chip with 3D microelectrodes, 3D microfluidics, interdigitated electrodes (IDEs) and a microheater. The chip was subsequently tested using the electrical/electrochemical characterization of 3D microelectrodes with 1 kHz impedance and phase recordings and IDE-based high-frequency (~1 MHz frequencies) impedimetric analysis of differential localized temperature recordings, both of which were modeled through equivalent electrical circuits for process parameter extraction. Additionally, a simplified antibody-conjugation strategy was employed for a similar IDE-based analysis of the implications of a key analyte (l-glutamine) binding to the equivalent electrical circuit. Finally, acute microfluidic perfusion modeling was performed to demonstrate the ease of microfluidics integration into such a polymer-metal biosensor platform for potential complimentary localized chemical stimulation. Overall, our work demonstrates the design, development, and characterization of an accessibly designed polymer-metal compound biosensor for electrogenic cellular constructs to facilitate comprehensive MPS data collection.
Benchtop tissue cultures have become increasingly complex in recent years, as more “on-a-chip” biological technologies such as Microphysiological Systems (MPSs) work to incorporate cellular constructs that more accurately represent their respective biological systems. Such MPSs have begun providing major breakthroughs in biological research and are poised to shape the field in the coming decades. These biological systems necessitate integrated sensing modalities to procure complex, multiplexed datasets, with unprecedented combinatorial biological detail. In this work we expand on our polymer-metal biosensor approach by demonstrating a facile technology towards compound biosensing which are characterized through custom modeling approaches. Herein we develop a compound chip with 3D microelectrodes, 3D microfluidics, Interdigitated Electrodes (IDEs) and a micro-heater. The chip is subsequently tested using electrical/electrochemical characterization of 3D microelectrodes with 1kHz impedance and phase recordings, and IDE-based high frequency (~ 1MHz frequencies) impedimetric analysis of differential localized temperature recordings, both of which are modelled through equivalent electrical circuits for process parameter extraction. Additionally, a simplified antibody-conjugation strategy was employed for a similar IDE-based analysis of the implications for a key analyte (L-Glutamine) binding on the equivalent electrical circuit. Lastly, acute microfluidic perfusion modelling was performed to demonstrate ease of microfluidics integration into such a polymer-metal biosensor platform for potential complimentary localized chemical stimulation. Combined, our work demonstrates the design, development, and characterization of an accessibly designed, polymer-metal compound biosensor for electrogenic cellular constructs, geared towards comprehensive MPS data collection.
Advances within in vitro biological system complexity have enabled new possibilities for the "Organs-on-a-Chip" field. Microphysiological systems (MPS) as such incorporate sophisticated biological constructs with custom biological sensors. For microelectromechanical systems (MEMS) sensors, the dielectric layer is critical for device performance, where silicon dioxide (SiO 2 ) represents an excellent candidate due to its biocompatibility and wide utility in MEMS devices. Yet, high temperatures traditionally preclude SiO 2 from incorporation in polymer-based BioMEMS. Electron-beam deposition of SiO 2 may provide a lowtemperature, dielectric serving as a nanoporous MPS growth substrate. Herein, we enable improved adherence of nanoporous SiO 2 to polycarbonate (PC) and 316L stainless steel (SS) via polydopamine (PDA)-mediated chemistry. The resulting stability of the combinatorial PDA−SiO 2 film was interrogated, along with the nature of the intrafilm interactions. A custom polymer−metal three-dimensional (3D) microelectrode array (3D MEA) is then reported utilizing PDA−SiO 2 insulation, for definition of novel dorsal root ganglion (DRG)/nociceptor and dorsal horn (DH) 3D neural constructs in excess of 6 months for the first time. Spontaneous/evoked compound action potentials (CAPs) are successfully reported. Finally, inhibitory drugs treatments showcase pharmacological responsiveness of the reported multipart biological activity. These results represent the initiation of a novel 3D MEA-integrated, 3D neural MPS for the long-term electrophysiological study.
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