Organ-on-chip devices have provided the pharmaceutical and tissue engineering worlds much hope since they arrived and began to grow in sophistication. However, limitations for their applicability were soon realized as they lacked real-time monitoring and sensing capabilities. The users of these devices relied solely on endpoint analysis for the results of their tests, which created a chasm in the understanding of life between the lab the natural world. However, this gap is being bridged with sensors that are integrated into organ-on-chip devices. This review goes in-depth on different sensing methods, giving examples for various research on mechanical, electrical resistance, and bead-based sensors, and the prospects of each. Furthermore, the review covers works conducted that use specific sensors for oxygen, and various metabolites to characterize cellular behavior and response in real-time. Together, the outline of these works gives a thorough analysis of the design methodology and sophistication of the current sensor integrated organ-on-chips.

Presented here is a scalable and aqueous phase exfoliation of graphite to high yield and quality of few layer graphene (FLG) using Bovine Serum Albomine (BSA) and wet ball milling. The produced graphene ink is tailored for printable and flexible electronics, having shown promising results in terms of electrical conductivity and temporal stability. Shear force generated by steel balls which resulted in 2–3 layer defect-free graphene platelets with an average size of hundreds of nm, and with a concentration of about 5.1 mg/mL characterized by Raman spectroscopy, atomic force microscopy (AFM), transmittance electron microscopy (TEM) and UV-vis spectroscopy. Further, a conductive ink was prepared and printed on flexible substrate (Polyimide) with controlled resolution. Scanning electron microscopy (SEM) and Profilometry revealed the effect of thermal annealing on the prints to concede consistent morphological characteristics. The resulted sheet resistance was measured to be ${\mathrm{R}}_{\mathrm{s}}=36.75 \mathsf{\Omega }/\mathrm{sqr}$ for prints as long as 100 mm. Printable inks were produced in volumes ranging from 20 mL to 1 L, with potential to facilitate large scale production of graphene for applications in biosensors, as well as flexible and printable electronics.

Parkinson’s disease (PD) is the second most common neurodegenerative disease in the United States after Alzheimer’s disease (AD). To help understand the electrophysiology of these diseases, N27 neuronal cells have been used as an in vitro model. In this study, a flexible graphene-based biosensor design is presented. Biocompatible graphene was manufactured using a liquid-phase exfoliation method and bovine serum albumin (BSA) for further exfoliation. Raman spectroscopy results indicated that the graphene produced was indeed few-layer graphene (FLG) with ${\left(I_D/I_G\right)}_{Graphene}=$ 0.11. Inkjet printing of this few-layer graphene ink onto Kapton polyimide (PI) followed by characterization via scanning electron microscopy (SEM) showed an average width of ≈868 µm with a normal thickness of ≈5.20 µm. Neuronal cells were placed on a thermally annealed 3D printed graphene chip. A live–dead cell assay was performed to prove the biosensor biocompatibility. A cell viability of approximately 80% was observed over 96 h, which indicates that annealed graphene on Kapton PI substrate could be used as a neuronal cell biosensor. This research will help us move forward with the study of N27 cell electrophysiology and electrical signaling.

Dopamine is critical for the physiological function and plays a crucial role in the discovery of neurological disorders such as Parkinson's disease. Improving the measurement of this neurotransmitter could improve treatment, diagnosis, and prognosis of neurological disorders. Graphene's outstanding biocompatibility and electrical conductivity have caused it to become a widely used material in cellular interfacing and neurotransmitter characterization. However, graphene has been rarely used to investigate cellular systems after introducing trauma. Sensing dopamine on the cellular level and on the microscale can lead to provide a point-of-care diagnostics for traumatic brain injury patients. The sensitivity of graphene biosensor to different concentrations of dopamine was evaluated in the dynamic range of 0.1–100 µM, and the limit of detection of biosensor was estimated to be 180 µM. In this work, a 3D-printed graphene biosensor was used to characterize the dopamine levels as a real-time detector of neurotransmitters. We used cyclic voltammetry (CV) to measure the response of graphene biosensors to neurotransmitter changes, in addition, to evaluate the effect of UV irradiation as the injury stimulant on the electrical properties of graphene biosensors. We demonstrated that the 3D-printed graphene could detect significant changes in the CV profiles of N27 dopaminergic neural cells cultured on the graphene device in the face of trauma.