To appreciate why this matters, it helps to understand what a nanopore sensor actually does. The principle is deceptively simple: a membrane thin enough and porous enough to present a single nanoscale opening separates two fluid reservoirs. When a voltage is applied, ions flow through the pore, producing a steady baseline current. When a molecule—say, a strand of DNA or an individual protein—passes through the opening, it briefly blocks or modulates that current. Because each molecule disturbs the ionic flow in a way that reflects its size, shape, and charge, the sensor can identify and characterize molecules one at a time, without the chemical labeling or amplification steps that many conventional assays require. The smaller and more precisely controlled the opening, the finer the discrimination the device can achieve.

The work, led by doctoral student Xinxin Liu and professor Frank Niklaus of KTH’s Division of Micro and Nanosystems, addresses a well-recognized bottleneck in the fabrication of nano-scale openings in thin membranes. A typical sensor device uses a membrane with a single nanopore, which functions as a detector for individual molecules. Because these openings must be carved with extraordinary precision, they are currently produced one at a time using techniques such as electron-beam drilling and sculpting with a Transmission Electron Microscope (TEM). Both approaches are slow, expensive, and difficult to scale to industrial volumes—limitations that have kept nanopore-based sensing from reaching its full potential outside of well-funded laboratories.

The economics of these legacy methods are worth spelling out. An electron microscope capable of drilling a hole a few nanometers wide represents a capital investment in the millions of dollars, and each pore requires an operator-guided session of beam exposure, imaging, and verification. A skilled technician might spend hours producing a handful of usable devices, and every additional pore multiplies the time and cost. That arithmetic is tolerable when the goal is a research prototype; it becomes prohibitive when the goal is thousands or millions of sensors for clinics, laboratories, or field-deployable diagnostic kits. The mismatch between how nanopores are made and how many of them the growing field demands has been one of the quiet constraints on the technology’s expansion.

Niklaus says the study demonstrates a fundamentally different approach: using built-in mechanical stress to create the nanoholes. Rather than removing material with a beam of electrons or ions, the KTH team lets physics do the work. The technique exploits fracture mechanics—the same rules that govern how materials crack and tear—to generate openings in the sensor membrane, and it does so across many sites on a wafer simultaneously, producing large arrays of nanopores in parallel.

The process begins with a stack of layers deposited on a silicon wafer. The top layer is deliberately placed under tension, stretched like a drawn rubber band. Beneath it sits a second layer of material that is etched away until only a small, pre-defined shape remains. This remnant acts as an anchor and is meant to define the shape of the nanopore that will ultimately form in the third layer underneath—the sensor membrane itself. When the tension in the top layer is released, the stressed layer behaves like a rope attached to that anchor.

“The beam pulls on until it tears a nanoscale fragment from the membrane, creating the hole,” Liu says. She offers a vivid analogy for the mechanism: it is much like removing a tree stump with a rope. The stressed beam attaches to the nanoscale anchor, pulling it away from the membrane, which serves as the ground. As the anchor is wrenched free, it tears a fragment out of the membrane, leaving behind a hole whose dimensions are dictated by the lithographically defined anchor shape. The image of uprooting stumps is more than a flourish—it captures the essential physics of a tensile failure event harnessed as a manufacturing step.

The elegance of the scheme lies in how it converts an engineering liability into an asset. Mechanical stress in thin films is ordinarily something chipmakers work hard to manage and minimize, because uncontrolled stress can warp wafers, delaminate layers, and crack devices. Instead of suppressing it, the KTH team engineers it deliberately, tuning the tension so that fracture occurs exactly where and when it is wanted. Every structural element involved—the stressed beam, the sacrificial anchor, the membrane—is defined by standard lithographic patterning, which means the geometry of each future pore is set down in advance by the same design files that govern the rest of the chip. Fracture, a phenomenon usually treated as a failure mode, becomes a deterministic manufacturing step.

What makes the result notable is not just the elegance of the analogy but the breadth of its applicability. The researchers tested the technique successfully in multiple materials, including dielectric, metallic, and semiconductor sensor membranes. That versatility matters because different sensing applications favor different membrane materials, and a method confined to a single material system would have limited reach. Some sensing chemistries work best with insulating dielectrics; others benefit from the conductive properties of metals or the semiconductor behavior of silicon-based films. The study also shows that the resulting nanopores were effective at DNA analysis and molecule detection, demonstrating that pores made this way are not merely structural curiosities but functional components of working sensors.

The significance of parallel fabrication is hard to overstate for the field. Nanopores are valuable tools because their extremely small openings in ultra-thin materials can be used to detect and analyze individual molecules such as DNA and proteins. They underpin a range of sensing and analysis technologies used in medical research and, increasingly, in specialized clinics where sequencing systems are deployed for outbreak surveillance, cancer genomics, and infectious disease identification, among other applications. If the pores at the core of these instruments can be mass-produced on standard semiconductor lines rather than sculpted one by one under an electron microscope, the cost and availability of such systems could shift substantially.

The route toward commercialization is already under way. Liu says the researchers have patented the technique and formed a startup to progress it toward commercial implementation. “We have already shipped samples to a collaborator for testing, so it has moved beyond the lab stage,” she says. That step—from demonstration to external evaluation—is often where promising fabrication methods stall, and the team’s early move to put devices in a collaborator’s hands suggests confidence that the process can survive contact with real-world requirements.

The publication itself carries the hallmarks of a carefully documented study. Appearing in a peer-reviewed journal with a formal article title and digital object identifier, the work positions the stress-driven fracture method alongside established nanofabrication techniques as a credible alternative rather than a laboratory demonstration destined to remain on the bench. The researchers’ framing of the method as compatible with conventional semiconductor manufacturing is central to its promise: wafer-scale processes, layer deposition, and lithographic patterning are the stock-in-trade of the chip industry, and a nanopore method built from those same ingredients inherits decades of industrial maturity. Semiconductor fabs routinely pattern features far smaller than the anchors and beams involved here, deposit thin films with precisely controlled stress states, and inspect finished wafers with automated optical tools. Borrowing that infrastructure means the marginal cost of each additional pore on a wafer falls toward the cost of the lithography itself—which is to say, toward very little.

For the clinics and research laboratories that depend on nanopore sensing, the implications could be far-reaching. Sequencing systems used for outbreak surveillance need to be deployable quickly and at scale; cancer genomics and infectious disease identification benefit from lower per-instrument costs; and medical research labs without access to specialized nanofabrication facilities could gain access to sensors that were previously out of reach. A method that turns nanopore fabrication from an artisanal craft into a batch process aligns with exactly those needs. It also opens the possibility of designing devices with many pores operating in parallel on a single chip, multiplying throughput in the same way that arrays of sensors have transformed other areas of diagnostics.

There are, of course, caveats worth keeping in view. The study reports pores in the range of roughly 6 to 10 nanometers, which is well suited to many single-molecule applications, but the full distribution of pore sizes achievable across a wafer, the long-term stability of stress-engineered membranes, and the yield of usable devices in high-volume production remain questions that commercialization will need to answer. Single-molecule sensing is unforgiving of variability: even small differences in pore dimensions can shift signal characteristics from device to device, and any manufacturing method intended for scale must demonstrate tight, repeatable control. Fracture, for all its determinism in principle, is a physical event with inherent statistical character, and characterizing how tightly it performs across thousands of sites on a wafer will be an essential part of the industrialization story. The researchers’ own decision to ship samples for external testing acknowledges that laboratory performance must be validated by independent users before the method can be considered proven at scale.

Still, the core achievement stands: a way to make nanoscale holes by pulling, rather than drilling—harnessing built-in stress and fracture mechanics to tear open pores defined by lithography, in parallel, across multiple material systems. Like the tree stump that yields to a well-anchored rope, a stubborn fabrication bottleneck has been dislodged by applying force in the right place. If the technique continues to advance through patenting, startup development, and collaborator testing, the sensors that detect individual DNA strands and proteins may soon be made the way computer chips are: by the wafer, in the thousands, far from the cleanrooms where they were once coaxed into existence one pore at a time.

Traditional approaches to flexible electrodes have typically relied on wavy or serpentine designs to accommodate mechanical deformation. While these structures provide some degree of stretchability, they often suffer from stress concentration at the waves’ apexes, leading to accelerated mechanical fatigue and eventual failure during long-term use. Conversely, microcracked electrodes offer excellent stretchability by dispersing strain via crack propagation but risk intermittent conductivity loss due to microcrack growth. The HMS developed here cleverly integrates both principles, positioning microcracks at the peaks and troughs of the wavy gold electrodes deposited on flexible substrates. This hybridization results in efficient stress relaxation mechanisms, ensuring electrodes endure repeated large strains without compromising electrical performance.

The fabrication of these electrodes involves depositing gold on elastomeric substrates patterned into wavy geometries, followed by controlled induction of microcracks that run orthogonally to the wave direction. Finite element mechanical simulations reveal that this configuration dramatically reduces localized strain and stress, effectively redistributing mechanical loads. Remarkably, the electrodes maintain stable electrical conductivity even after 5000 cycles of stretching to 60% strain, a durability benchmark far surpassing previous flexible biosensors. This longevity is critical for real-world applications, where devices must reliably function amid the constant, complex mechanical stresses induced by bodily movements.

To transform these mechanically resilient electrodes into multifunctional biosensors, the researchers functionalized them with conductive polymers tailored for specific analyte detection. PEDOT:PSS coatings confer selective sensitivity to electrolyte ions such as calcium (Ca²⁺), sodium (Na⁺), and potassium (K⁺), which are vital indicators of hydration and metabolic status. Meanwhile, polyaniline (PANI)-based layers enable precise pH measurement, a parameter that reflects changes in sweat composition related to acid-base balance and physiological stress. These coatings preserve their sensing capabilities even under significant mechanical deformation, demonstrating exceptional electromechanical coupling within the HMS framework.

The entire sensor assembly is encapsulated in ultrathin films of Styrene-Ethylene-Butylene-Styrene (SEBS), which impart additional mechanical robustness and skin compatibility without sacrificing stretchability or breathability. The thin, soft encapsulation ensures conformal contact to the skin surface, minimizing motion artifacts that often plague wearable electronics. This design consideration is paramount for accurate, continuous biomarker monitoring during physical activities, including high-intensity exercise.

In human trials, a volunteer wore the integrated HMS biosensor during a sustained 20-minute running session. Throughout the exercise, the device accurately tracked transient fluctuations in sweat ion concentrations and muscle electromyography (EMG) signals in real time. The EMG data provide insights into muscle activation patterns and fatigue levels, complementing the biochemical markers drawn from sweat analysis. The sensor’s performance underscores its potential utility in sports science and rehabilitation, offering athletes and clinicians a powerful tool for monitoring physiological responses dynamically.

The combination of mechanical flexibility, chemical selectivity, and electrical reliability embodied in the HMS biosensors addresses longstanding barriers in wearable health technology. Prior devices often forced trade-offs between stretchability and multiplexed sensing, limiting their broader applicability. By contrast, this hybrid microstructure enables robust device operation under real-world, high-strain conditions while simultaneously capturing diverse biological signals on a single platform. This represents a pivotal step forward in the integration of multifunctional sensors for personalized health surveillance and management.

Professor Zhiyuan Liu, senior author of this study, emphasized the transformative potential of the HMS design, characterizing it as a “game-changer” that bridges a critical gap between mechanical adaptability and rich functional sensing. This innovation not only meets the rigorous demands of continuous, non-invasive monitoring but also expands the horizons of wearable technology applications. From tracking dehydration and electrolyte imbalances to detecting early muscular fatigue and potentially signaling disease onset, these sensors promise to empower proactive and data-driven healthcare.

Looking ahead, the research team aims to further refine this technology by enhancing breathability and scalability while integrating wireless communication modules for seamless connectivity. Such developments will facilitate the embedding of HMS biosensors into everyday garments or skin patches, promoting unobtrusive health monitoring in a variety of contexts—from athletic performance optimization to chronic disease management. The ability to concurrently monitor multiple physiological parameters in real time makes these biosensors ideally suited for the rapidly evolving landscape of digital health and personalized medicine.

The implications of this advancement extend well beyond consumer health, touching on broader societal challenges such as aging population management, remote patient monitoring, and occupational health surveillance. By enabling continuous, multimodal data acquisition without restricting user mobility, HMS biosensors could revolutionize how clinicians and individuals make informed decisions about wellness and intervention strategies. Such technologies could usher in a new paradigm where healthcare shifts from episodic assessments to continuous, anticipatory guidance.

In summary, the marriage of wave-like electrode structures with strategically engineered microcracks fosters a novel class of stretchable, multifunctional biosensors with unparalleled mechanical and sensing reliability. The integration of conductive polymer functionalization and thin-film encapsulation further enhances the device’s sensitivity and durability. As these versatile biosensors transition toward commercialization, they hold immense promise for revolutionizing personalized health monitoring, advancing scientific understanding of physiological processes, and ultimately improving quality of life across diverse populations.

Subject of Research: Advanced stretchable biosensors with hybrid microstructure electrodes for multimodal physiological monitoring

Article Title: Hybrid Microstructure Enables Highly Stretchable, Multifunctional Biosensors for Real-Time Sweat Ion, pH, and EMG Monitoring

News Publication Date: March 2025

Web References:

• https://www.sciencedirect.com/science/article/pii/S2667141724001265
• https://www.sciencedirect.com/journal/escience

References:
DOI: 10.1016/j.esci.2024.100327

Image Credits: Zhiyuan Liu, et al

Keywords: Microstructures, Stretchable biosensors, Hybrid microstructure, EMG sensing, Sweat ion monitoring, pH sensors, Conductive polymers, PEDOT:PSS, Polyaniline, Flexible electronics, Wearable health monitoring