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1. Three-dimensional microscale hanging drop arrays with geometric control for drug screening and live tissue imaging

   https://doi.org/10.1126/sciadv.abc1323  

   Ganguli, A.; Mostafa, A.; Saavedra, C.; Kim, Y.; Le, P.; Faramarzi, V.; Feathers, R. W.; Berger, J.; Ramos-Cruz, K. P.; Adeniba, O.; et al (April 2021, Science Advances)

   null (Ed.)

   Existing three-dimensional (3D) culture techniques are limited by trade-offs between throughput, capacity for high-resolution imaging in living state, and geometric control. Here, we introduce a modular microscale hanging drop culture where simple design elements allow high replicates for drug screening, direct on-chip real-time or high-resolution confocal microscopy, and geometric control in 3D. Thousands of spheroids can be formed on our microchip in a single step and without any selective pressure from specific matrices. Microchip cultures from human LN229 glioblastoma and patient-derived mouse xenograft cells retained genomic alterations of originating tumors based on mate pair sequencing. We measured response to drugs over time with real-time microscopy on-chip. Last, by engineering droplets to form predetermined geometric shapes, we were able to manipulate the geometry of cultured cell masses. These outcomes can enable broad applications in advancing personalized medicine for cancer and drug discovery, tissue engineering, and stem cell research. 

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2. Deterministic Single Cell Encapsulation in Asymmetric Microenvironments to Direct Cell Polarity

   https://doi.org/10.1002/advs.202206014  

   Cho, Ik_Sung; Gupta, Prerak; Mostafazadeh, Nima; Wong, Sing_Wan; Saichellappa, Saiumamaheswari; Lenzini, Stephen; Peng, Zhangli; Shin, Jae‐Won (December 2022, Advanced Science)

   Abstract Various signals in tissue microenvironments are often unevenly distributed around cells. Cellular responses to asymmetric cell‐matrix adhesion in a 3D space remain generally unclear and are to be studied at the single‐cell resolution. Here, the authors developed a droplet‐based microfluidic approach to manufacture a pure population of single cells in a microscale layer of compartmentalized 3D hydrogel matrices with a tunable spatial presentation of ligands at the subcellular level. Cells elongate with an asymmetric presentation of the integrin adhesion ligand Arg‐Gly‐Asp (RGD), while cells expand isotropically with a symmetric presentation of RGD. Membrane tension is higher on the side of single cells interacting with RGD than on the side without RGD. Finite element analysis shows that a non‐uniform isotropic cell volume expansion model is sufficient to recapitulate the experimental results. At a longer timescale, asymmetric ligand presentation commits mesenchymal stem cells to the osteogenic lineage. Cdc42 is an essential mediator of cell polarization and lineage specification in response to asymmetric cell‐matrix adhesion. This study highlights the utility of precisely controlling 3D ligand presentation around single cells to direct cell polarity for regenerative engineering and medicine. 

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3. High-Speed 1024-Pixel CMOS Electrochemical Imaging Sensor with 40,000 Frames per Second for Dopamine and Hydrogen Peroxide Imaging

   https://doi.org/10.3390/electronics14163207  

   White, Kevin A; Crocker, Matthew A; Kim, Brian N (August 2025, Electronics)

   Electrochemical sensing arrays enable the spatial study of dopamine levels throughout brain slices, the diffusion of electroactive molecules, as well as neurotransmitter secretion from single cells. The integration of complementary metal-oxide semiconductor (CMOS) devices in the development of electrochemical sensing devices enables large-scale parallel recordings, providing beneficial high-throughput for drug screening studies, brain–machine interfaces, and single-cell electrophysiology. In this paper, an electrochemical sensor capable of recording at 40,000 frames per second using a CMOS sensor array with 1024 electrochemical detectors and a custom field-programmable gate array data acquisition system is detailed. A total of 1024 on-chip electrodes are monolithically integrated onto the designed CMOS chip through post-CMOS fabrication. Each electrode is paired with a dedicated transimpedance amplifier, providing 1024 parallel electrochemical sensors for high-throughput studies. To support the level of data generated by the electrochemical device, a powerful data acquisition system is designed to operate the sensor array as well as digitize and transmit the output of the CMOS chip. Using the presented electrochemical sensing system, both dopamine and hydrogen peroxide diffusions across the sensor array are successfully recorded at 40,000 frames per second across the 32 × 32 electrochemical detector array. 

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4. Modular cone-and-plate device for mechanofluidic assays in Transwell inserts

   https://doi.org/10.3389/fbioe.2025.1494553  

   Chavarria, Daniel; Georges, Kissamy A; O’Grady, Brian J; Hassan, Khalid K; Lippmann, Ethan S (January 2025, Frontiers in Bioengineering and Biotechnology)

   In this work, we present a cost effective and open-source modular cone-and-plate (MoCAP) device that incorporates shear stress in the popular Transwell^®insert system. This system acts as a lid that incorporates flow into 24-well Transwell^®inserts while preserving the ability to conduct molecular profiling assays. Moreover, the MoCAP device can be rapidly reconfigured to test multiple shear stress profiles within a single device. To demonstrate the utility of the MoCAP, we conducted select assays on several different brain microvascular endothelial cell (BMEC) lines that comprise models of the blood-brain barrier (BBB), since shear stress can play an important role in BBB function. Our results characterize how shear stress modulates passive barrier function and GLUT1 expression across the different BMEC lines. Overall, we anticipate this low cost mechanofluidic device will be useful to the mechanobiology community. 

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5. Biocompatible 3D Printed MXene Microlattices for Tissue‐Integrated Antibiotic Sensing

   https://doi.org/10.1002/admt.202301517  

   Tiwari, Anand_P; Panicker, Sreejith_S; Huddy, Julia_E; Rahman, Md_Saifur; Hixon, Katherine_R; Scheideler, William_J (December 2023, Advanced Materials Technologies)

   Abstract 3D continuous mesoscale architectures of nanomaterials possess the potential to revolutionize real‐time electrochemical biosensing through higher active site density and improved accessibility for cell proliferation. Herein, 3D microporous Ti₃C₂T_XMXene biosensors are fabricated to monitor antibiotic release in tissue engineering scaffolds. The Ti₃C₂T_X‐coated 3D electrodes are prepared by conformal MXene deposition on 3D‐printed polymer microlattices. The Ti₃C₂T_XMXene coating facilitates direct electron transfer, leading to the efficient detection of common antibiotics such as gentamicin and vancomycin. The 3D microporous architecture exposes greater electrochemically active MXene surface area, resulting in remarkable sensitivity for detecting gentamicin (10–1 mM) and vancomycin (100–1 mM), 1000 times more sensitive than control electrodes composed of 2D planar films of Ti₃C₂T_XMXene. To characterize the suitability of 3D microporous Ti₃C₂T_XMXene sensors for monitoring drug elution in bone tissue regeneration applications, osteoblast‐like (MG‐63) cells are seeded on the 3D MXene microlattices for 3, 5, and 7 days. Cell proliferation on the 3D microporous MXene is tracked over 7 days, demonstrating its promising biocompatibility and its clinical translation potential. Thus, 3D microporous Ti₃C₂T_XMXene can provide a platform for mediator‐free biosensing, enabling new applications for in vivo monitoring of drug elution. 

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