M13 bacteriophage is a promising biomolecule capable of various bionano and material science applications. The biomaterial can self-assemble into matrices to fabricate bioscaffolds using high phage concentration and high phage purity. Previous studies aimed to acquire these conditions in large-scale phage production and have identified the optimal culture temperature range at 28–31 °C. However, explanations as to why this temperature range was optimal for phage production is absent from the work. Therefore, in this study, we identified the relation between culture temperature and M13 phage production using ATP expenditure calculations to comprehend the high yield phage production at the optimal temperature range. We extended a coarse-grained model for the evaluation of phage protein and ribosomal protein synthesis with the premise that phage proteins (a ribosomal protein) are translated by bacterial ribosomes in E. coli through expenditure of ATP energy. By comparing the ATP energy for ribosomal protein synthesis estimated using the coarse-grained model and the experimentally calculated ATP expenditure for phage production, we interpreted the high phage yield at the optimal temperature range and recognized ATP analysis as a reasonable method that can be used to evaluate other parameters for phage production optimization.

Three-dimensional (3D) organoids provide physiologically relevant models for studying human neural development and disease; however, stable bioelectronic interfacing with curved and dynamic organoid surfaces remains challenging. Here, we present a thermally actuated, shape-memory polymer (SMP)-based foldable bioelectronic interface for simultaneous electrophysiological recording and electrochemical cytokine sensing in human spinal cord organoids (hSCOs). Near physiological temperature (36-37 °C), the SMP substrate undergoes pronounced mechanical softening, enabling conformal 3D wrapping around organoids without external mechanical compression. The platform integrates gold microelectrodes for extracellular neural recording and antibody-functionalized sensing electrodes for label-free cytokine detection. Finite element simulations and experimental mechanical analyses confirmed temperature-dependent bending, enhanced conformal contact, low interfacial stress, and mechanically stable biointerfacing. Electrochemical characterization demonstrated linear cytokine sensing responses over 1-100 ng/ml, with calculated limits of detection (LOD) of 0.44 ng/ml for TNF-α and 0.41 ng/ml for IL-8. Using this multimodal platform, stable electrophysiological recordings and cytokine monitoring were simultaneously obtained from hSCOs under inflammatory stimulation. TNF-α treatment induced dose-dependent increases in neural firing activity together with corresponding electrochemical cytokine responses. Collectively, this thermally adaptive bioelectronic interface provides a minimally invasive platform for integrated electrical and biochemical profiling of intact organoids and offers a promising tool for neuroinflammatory organoid studies.

Three-dimensional (3D) organoids are powerful in vitro models for studying human physiology and disease. However, their irregular geometries and dynamic microenvironments pose significant challenges for stable and comprehensive bioelectronic interrogation. Here, we present a thermally actuated, shape-memory polymer (SMP)-based foldable bioelectronic interface that enables conformal 3D interfacing with human spinal cord organoids for simultaneous electrophysiological recording and cytokine sensing. The interface undergoes temperature-induced mechanical softening near physiological conditions, allowing it to wrap around organoids and establish close contact with their curved surfaces. Additionally, selective antibody immobilization on designated electrodes enables concurrent acquisition of electrical and biochemical signals. Finite element simulation and experimental validation confirmed temperature-dependent bending, controlled stress distribution, and mechanically safe interfacial integration under biologically relevant conditions. Furthermore, the platform allows quantitative analysis of cytokine concentrations in a dose-dependent manner. Using this system, stable electrophysiological recordings were obtained from organoids under both basal and inflammatory conditions. TNF-α stimulation induced dose-dependent modulation of neural activity, consistent with corresponding cytokine dynamics during inflammation. Overall, this multimodal bioelectronic interface enables integrated electrical and biochemical profiling of intact organoids, providing a conformal and minimally invasive platform for functional organoid assessment.