Dandin, M. P. | bioRxiv Science

bioRxiv2025

Evaporation and Focus Degradation Mitigation in In-Incubator Live Cell Imaging for Capacitance Lab-on-CMOS Microsystem Calibration

Lab-on-CMOS is an instrumentation technology that combines miniaturized bioanalytical hardware with complementary metal-oxide semiconductor (CMOS) electronics to provide integrated biosensing in a compact format. This paper focuses on a class of lab-on-CMOS systems that utilize capacitance sensing as a means to monitor cell cultures and track cell proliferation, as well as other cell life-cycle events. In this paradigm, changes in interfacial capacitance result from the activity of adherent cells at a bioelectronic interface. These changes are mapped to cell proliferation or life-cycle events using a ground-truth measurement such as live cell imaging from real-time microscopy. This paper identifies instrumentation challenges that arise from conducting these ground-truth measurements in a calibrated cell culture environment, i.e., when the lab-on-CMOS system is deployed inside a CO2 cell culture incubator. We show that autofocusing the microscopy column and provisioning the lab-on-CMOS with an immersion lid are two approaches that significantly improve the quality of live cell imaging ground-truth measurements over long periods.

bioengineering↗

bioRxiv2023

Capacitance measurements for assessing DNA origami nanostructures

Nanostructures fabricated with DNA are emerging as a practical approach for applications ranging from advanced manufacturing to therapeutics. To support the strides made in improving accessibility and facilitating commercialization of DNA nanostructure applications, we identify the need for a rapid characterization approach that aids nanostructure production. In our work, we introduce a low-fidelity characterization approach that provides an interdependent assessment of DNA origami formation, concentration and morphology using capacitance sensing. Change in charge is one of the transduction methods to determine capacitive loading on a substrate. It is known that cations in the solution stabilize DNA origami nanostructures. So, we hypothesized that the presence of cations and nanostructures in a buffer solution can induce capacitance change that is distinctive of the nanostructure present. In this study we were able to detect a change in the capacitance when the nanostructure solution was deposited on our capacitance sensor, and we could distinguish between pre-annealed and annealed structures at concentrations less than 15 nM. The capacitance measurements were affected by the concentration of Mg2+ ions in the solution, the staple-to-scaffold stoichiometric ratio of the nanostructure and the nanostructure morphology. Maintaining a 12.5 mM Mg2+ concentration in the nanostructure buffer, we discover a linear relationship between the relative capacitance change and the nanostructure concentration from 5 nM to 20 nM, which we call the characteristic curve. We find distinct characteristic curves for our three nanostructures with distinct morphologies but similar molecular weight - a rectangular plate, a sphere and a rod. Given that we can distinguish nanostructure formation, concentration and morphology, we expect that capacitance measurement will emerge as an affordable and rapid approach for quality control for nanostructure production.

bioengineering↗