Flexible biocompatible electronic systems that leverage key materials and manufacturing techniques associated with the consumer electronics industry have potential for broad applications in biomedicine and biological research. This study reports scalable approaches to technologies of this type, where thin microscale device components integrate onto flexible polymer substrates in interconnected arrays to provide multimodal, high performance operational capabilities as intimately coupled biointerfaces. Specificially, the material options and engineering schemes summarized here serve as foundations for diverse, heterogeneously integrated systems. Scaled examples incorporate >32,000 silicon microdie and inorganic microscale light-emitting diodes derived from wafer sources distributed at variable pitch spacings and fill factors across large areas on polymer films, at full organ-scale dimensions such as human brain, over ∼150 cm². In vitro studies and accelerated testing in simulated biofluids, together with theoretical simulations of underlying processes, yield quantitative insights into the key materials aspects. The results suggest an ability of these systems to operate in a biologically safe, stable fashion with projected lifetimes of several decades without leakage currents or reductions in performance. The versatility of these combined concepts suggests applicability to many classes of biointegrated semiconductor devices. Significance Emerging classes of flexible electronic systems designed to interface to soft tissues of the human body serve as the foundations for bioelectronic forms of medicine, with capabilities that can complement those of traditional pharmaceutical approaches. This work establishes the engineering science of categories of biointegrated microsystems that include assemblies of tens of thousands of microdevices interconnected into functional networks on thin flexible polymer substrates with areas that approach those of the human brain. Detailed in vitro studies suggest the ability of these systems to provide sophisticated electronic and optoelectronic function with stable, biologically safe operation for many decades. The results define concepts and technological approaches with widespread utility in the field of bioelectronics.

A critical challenge lies in the development of the next‐generation neural interface, in mechanically tissue‐compatible fashion, that offer accurate, transient recording electrophysiological (EP) information and autonomous degradation after stable operation. Here, an ultrathin, lightweight, soft and multichannel neural interface is presented based on organic‐electrochemical‐transistor‐(OECT)‐based network, with capabilities of continuous high‐fidelity mapping of neural signals and biosafety active degrading after performing functions. Such platform yields a high spatiotemporal resolution of 1.42 ms and 20 µm, with signal‐to‐noise ratio up to ≈37 dB. The implantable OECT arrays can well establish stable functional neural interfaces, designed as fully biodegradable electronic platforms in vivo. Demonstrated applications of such OECT implants include real‐time monitoring of electrical activities from the cortical surface of rats under various conditions (e.g., narcosis, epileptic seizure, and electric stimuli) and electrocorticography mapping from 100 channels. This technology offers general applicability in neural interfaces, with great potential utility in treatment/diagnosis of neurological disorders.