Two-dimensional (2D) cell culture techniques are commonly employed to investigate biophysical and biochemical cellular responses. However, these culture methods, having monolayer cells, lack cell-cell and cell-extracellular matrix interactions, mimicking the cell microenvironment and multicellular organization. Three-dimensional (3D) cell culture methods enable equal transportation of nutrients, gas, and growth factors among cells and their microenvironment. Therefore, 3D cultures show similar cell proliferation, apoptosis, and differentiation properties to in vivo. A spheroid is defined as self-assembled 3D cell aggregates, and it closely mimics a cell microenvironment in vitro thanks to cell-cell/matrix interactions, which enables its use in several important applications in medical and clinical research. To fabricate a spheroid, conventional methods such as liquid overlay, hanging drop, and so forth are available. However, these labor-intensive methods result in low-throughput fabrication and uncontrollable spheroid sizes. On the other hand, microfluidic methods enable inexpensive and rapid fabrication of spheroids with high precision. Furthermore, fabricated spheroids can also be cultured in microfluidic devices for controllable cell perfusion, simulation of fluid shear effects, and mimicking of the microenvironment-like in vivo conditions. This review focuses on recent microfluidic spheroid fabrication techniques and also organ-on-a-chip applications of spheroids, which are used in different disease modeling and drug development studies.

This paper presents a low-profile and autonomous piezoelectric energy harvesting system consisting of an extraction rectifier and a maximum power point tracking (MPPT) circuit for powering portable electronics. Synchronized switch harvesting on capacitor-inductor (SSHCI) technique with its unique two-step voltage flipping process is utilized to downsize the ponderous external inductor and extend application areas of such harvesting systems. SSHCI implementation with small flipping inductor-capacitor combination enhances voltage flipping efficiency and accordingly attains power extraction improvements over conventional synchronized switch harvesting on inductor (SSHI) circuits utilizing bulky external components. A novel MPPT system provides robustness of operation against changing load and excitation conditions. Innovation in MPPT comes from the refresh unit, which continually monitors excitation conditions of piezoelectric harvester to detect any change in optimum storage voltage. Compared with conventional circuits, optimal flipping detection inspired from active diode structures eliminates the need for external adjustment, delivering autonomy to SSHCI. Inductor sharing between SSHCI and MPPT reduces the number of external components. The circuit is fabricated in 180 nm CMOS technology with 1.23 mm ² active area, and is tested with custom MEMS piezoelectric harvester at its resonance frequency of 415 Hz. It is capable of extracting 5.44x more power compared to ideal FBR, while using $100~\mu $ H inductor. Due to reduction of losses through low power design techniques, measured power conversion efficiency of 83% is achieved at 3.2 V piezoelectric open circuit voltage amplitude. Boosting of power generation capacity in a low profile is a significant contribution of the design.

This paper presents an efficient hybrid energy harvesting interface to synergistically scavenge power from electromagnetic (EM) and piezoelectric (PE) sources, and drive a single load. The EM harvester output is rectified through a self-powered active doubler structure, and stored on a storage capacitor. The stored energy is then transferred to the PE harvester to increase the damping force and charge extraction. The total synergistically extracted power from both harvesters is more than the power obtained from each independently. The hybrid operation is validated through a compact and wearable platform that includes custom designed EM and PE harvesters for scavenging energy from human motion. The system supplies 1-3.4 V output for powering up wireless sensor nodes with a wide range of vibration frequency, and generates between 1-100 μW at 90% maximum power conversion efficiency. The solution has superior power generation performance compared to previous stand-alone systems in the literature.