Solid-state nanopores in ultrathin (<20 nm) membranes enable label-free single-molecule sensing, but their adoption as sensors is limited by the lack of scalable manufacturing methods that deliver nanopores with single-nanometer reproducibility. Self-limiting metal-assisted chemical etching (MACE) in silicon-on-insulator (SOI) membranes offers a parallel wet-chemical route for nanopore fabrication, yet prior demonstrations lacked a predictive design rule and required electron microscopy or electrical tests for confirming presence and number of pores. Here, we convert self-limiting MACE into a manufacturing-oriented workflow with optical process control to obtain and verify the formation of 4 nm nanopores in a scalable fashion. We decouple the deposition of 200 ± 10 nm gold (Au) nanoparticles from etching, enabling independent optimization of the two steps. The nanoparticle size allows for particle-per-membrane counting by dark-field optical microscopy, so that deposition can be repeated when counts are below target. We then map etching behavior across Au nanoparticle diameter d (10–200 nm) and silicon (Si) device-layer thickness t (5–18 nm), finding that d/t ≥ 0.8 ratio predicts self-limiting MACE behavior, where pore diameter becomes independent of particle size. In this regime, 200 ± 10 nm catalysts yield 4 ± 1 nm pores, corresponding to a reduction of ~50× in pore diameter and ~10× in pore-diameter variability compared to the catalyst diameter and related variability. Successful through-membrane pore formation produces undercuts in the buried oxide (typically ~200–300 nm diameter) beneath each pore, which can be characterized for each membrane by bright-field microscopy and used as proxy for the otherwise optically invisible 4 nm pores. Together, the predictive d/t framework and two-stage optical verification establish a scalable wet-chemical route to fabricate nanopores for biomolecular sensing and related nanofluidic devices.

Solid-state nanopores offer unique possibilities for biomolecule sensing; however, scalable production of sub-5 nm pores with precise diameter control remains a manufacturing challenge. In this work, we developed a scalable method to fabricate sub-5 nm nanopores in silicon (Si) nanomembranes through metal-assisted chemical etching (MACE) using gold nanoparticles. Notably, we present a previously unreported self-limiting effect that enables sub-5 nm nanopore formation from both 10 and 40 nm nanoparticles in the 12 nm thick monocrystalline device layer of a silicon-on-insulator substrate. This effect reveals distinctive etching dynamics in ultrathin Si nanomembranes, enabling precise control over nanopore dimensions. The resulting nanopore sensor, suspended over self-aligned spheroidal oxide undercuts with diameters of just a few hundred nanometers, exhibited low electrical noise and high stability due to encapsulation within dielectric layers. In DNA translocation experiments, our nanopore platform could distinguish folded and unfolded DNA conformations and maintained stable baseline conductance for up to 6 h, demonstrating both sensitivity and robustness. Our scalable nanopore fabrication method is compatible with wafer-level and batch processing and holds promise for advancing biomolecular sensing and analysis.

Nanopores in ultrathin membranes are central to single-molecule sensing, filtration, and energy conversion, yet fabrication of solid-state nanopores remains limited by fundamental trade-off between resolution, throughput, and tool complexity. Here, we report a scalable process that exploits stress-induced mechanical ripping in ultrathin membranes to detach a nanoscale membrane patch, enabling the deterministic formation of sub-lithographic nanopores scaling down to the sub-10 nm regime. Using this approach, we demonstrate wafer scale fabrication of nanopores at densities exceeding 10⁵ pores per cm² in dielectric (HfO₂), semiconducting (SiGe), and metallic (Cr) membranes, including suspended HfO₂ membranes as thin as 2 nm. We demonstrate the utility of the fabricated nanopores for high-performance surface enhanced Raman readouts of single molecule translocations. Beyond nanopore fabrication, this fracture-based approach points to broader opportunities for nanometer- and atomic-scale structuring of ultrathin materials.

Organic electrochemical transistors (OECTs) are promising devices for bioelectronics, such as biosensors. However, current cleanroom-based microfabrication of OECTs hinders fast prototyping and widespread adoption of this technology for low-volume, low-cost applications. To address this limitation, a versatile and scalable approach for ultrafast laser microfabrication of OECTs is herein reported, where a femtosecond laser to pattern insulating polymers (such as parylene C or polyimide) is first used, exposing the underlying metal electrodes serving as transistor terminals (source, drain, or gate). After the first patterning step, conducting polymers, such as poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS), or semiconducting polymers, are spin-coated on the device surface. Another femtosecond laser patterning step subsequently defines the active polymer area contributing to the OECT performance by disconnecting the channel and gate from the surrounding spin-coated film. The effective OECT width can be defined with high resolution (down to 2 µm) in less than a second of exposure. Micropatterning the OECT channel area significantly improved the transistor switching performance in the case of PEDOT:PSS-based transistors, speeding up the devices by two orders of magnitude. The utility of this OECT manufacturing approach is demonstrated by fabricating complementary logic (inverters) and glucose biosensors, thereby showing its potential to accelerate OECT research.

There is a growing interest to develop microfluidic bioreactors and organ-on-chipplatforms with integrated sensors to monitor their physicochemical properties and tomaintain a well-controlled microenvironment for cultured organoids. Conventionalsensing devices cannot be easily integrated with microfluidic organ-on-chip systemswith low-volume bioreactors for continual monitoring. This paper reports on thedevelopment of a multi-analyte optical sensing module for dynamic measurementsof pH and dissolved oxygen levels in the culture medium. The sensing system wasconstructed using low-cost electro-optics including light-emitting diodes and siliconphotodiodes. The sensing module includes an optically transparent window formeasuring light intensity, and the module could be connected directly to a perfusionbioreactor without any specific modifications to the microfluidic device design. Acompact, user-friendly, and low-cost electronic interface was developed to controlthe optical transducer and signal acquisition from photodiodes. The platformenabled convenient integration of the optical sensing module with a microfluidicbioreactor. Human dermal fibroblasts were cultivated in the bioreactor, and thevalues of pH and dissolved oxygen levels in the flowing culture medium were measuredcontinuously for up to 3 days. Our integrated microfluidic system providesa new analytical platform with ease of fabrication and operation, which can beadapted for applications in various microfluidic cell culture and organ-on-chipdevices.

Organ-on-a-chip systems areminiaturizedmicrofluidic 3D human tissue and organ models designed to recapitulate the important biological and physiological parameters of their in vivo counterparts. They have recently emerged as a viable platform for personalized medicine and drug screening. These in vitro models, featuring biomimetic compositions, architectures, and functions, are expected to replace the conventional planar, static cell cultures and bridge the gap between the currently used preclinical animal models and the human body. Multiple organoid models may be further connected together through the microfluidics in a similar manner in which they are arranged in vivo, providing the capability to analyze multiorgan interactions. Although a wide variety of human organ-on-a-chip models have been created, there are limited efforts on the integration of multisensor systems. However, in situ continual measuring is critical in precise assessment of the microenvironment parameters and the dynamic responses of the organs to pharmaceutical compounds over extended periods of time. In addition, automated and noninvasive capability is strongly desired for long-term monitoring. Here, we report a fully integrated modular physical, biochemical, and optical sensing platform through a fluidics-routing breadboard, which operates organ-on-a-chip units in a continual, dynamic, and automated manner.We believe that this platform technology has paved a potential avenue to promote the performance of current organ-on-a-chip models in drug screening by integrating a multitude of real-time sensors to achieve automated in situ monitoring of biophysical and biochemical parameters.