Standardizing designed and emergent quantitative features in microphysiological systems.

Microphysiological systems (MPSs) are cellular models that replicate aspects of organ and tissue functions in vitro. In contrast with conventional cell cultures, MPSs often provide physiological mechanical cues to cells, include fluid flow and can be interlinked (hence, they are often referred to as microfluidic tissue chips or organs-on-chips). Here, by means of examples of MPSs of the vascular system, intestine, brain and heart, we advocate for the development of standards that allow for comparisons of quantitative physiological features in MPSs and humans. Such standards should ensure that the in vivo relevance and predictive value of MPSs can be properly assessed as fit-for-purpose in specific applications, such as the assessment of drug toxicity, the identification of therapeutics or the understanding of human physiology or disease. Specifically, we distinguish designed features, which can be controlled via the design of the MPS, from emergent features, which describe cellular function, and propose methods for improving MPSs with readouts and sensors for the quantitative monitoring of complex physiology towards enabling wider end-user adoption and regulatory acceptance.

An organ-on-chip device with integrated charge sensors and recording microelectrodes.

Continuous monitoring of tissue microphysiology is a key enabling feature of the organ-on-chip (OoC) approach for in vitro drug screening and disease modeling. Integrated sensing units are particularly convenient for microenvironmental monitoring. However, sensitive in vitro and real-time measurements are challenging due to the inherently small size of OoC devices, the characteristics of commonly used materials, and external hardware setups required to support the sensing units. Here we propose a silicon-polymer hybrid OoC device that encompasses transparency and biocompatibility of polymers at the sensing area, and has the inherently superior electrical characteristics and ability to house active electronics of silicon. This multi-modal device includes two sensing units. The first unit consists of a floating-gate field-effect transistor (FG-FET), which is used to monitor changes in pH in the sensing area. The threshold voltage of the FG-FET is regulated by a capacitively-coupled gate and by the changes in charge concentration in close proximity to the extension of the floating gate, which functions as the sensing electrode. The second unit uses the extension of the FG as microelectrode, in order to monitor the action potential of electrically active cells. The layout of the chip and its packaging are compatible with multi-electrode array measurement setups, which are commonly used in electrophysiology labs. The multi-functional sensing is demonstrated by monitoring the growth of induced pluripotent stem cell-derived cortical neurons. Our multi-modal sensor is a milestone in combined monitoring of different, physiologically-relevant parameters on the same device for future OoC platforms.

Correction: Towards microwave imaging of cells.

Correction for 'Towards microwave imaging of cells' by Mehmet Kelleci et al., Lab Chip, 2018, DOI: 10.1039/c7lc01251a.

Towards microwave imaging of cells.

Integrated detection techniques that can characterize the morphological properties of cells are needed for the widespread use of lab-on-a-chip technology. Herein, we establish a theoretical and experimental framework to use resonant microwave sensors in their higher order modes so that the morphological properties of analytes inside a microfluidic channel can be obtained electronically. We built a phase-locked loop system that can track the first two modes of a microstrip line resonator to detect the size and location of microdroplets and cells passing through embedded microfluidic channels. The attained resolution, expressed in terms of Allan deviation at the response time, is as small as 2 × 10-8 for both modes. Additionally, simulations were performed to show that sensing with higher order modes can yield the geometrical volume, effective permittivity, two-dimensional extent, and the orientation of analytes. The framework presented here makes it possible to develop a novel type of microscope that operates at the microwave band, i.e., a radar for cells.