Recent advancements in micro-scaled light-emitting diode (LED) technology have catalyzed a paradigm shift in biomedical engineering, addressing critical challenges in disease monitoring, therapeutic interventions, and post-treatment rehabilitation.1^–4 Traditional medical devices often face limitations in precision, invasiveness, and adaptability, hindering their ability to meet the growing demand for personalized and minimally invasive healthcare solutions. For instance, conventional wearable sensors for physiological monitoring struggle with skin conformity and long-term usability, whereas existing optogenetic and phototherapeutic tools rely on bulky, energy-intensive systems that compromise patient mobility and comfort.5^,6

Micro-scaled LEDs, characterized by their ultra-compact size, low power consumption, and tunable light emission, offer a versatile platform to overcome these barriers.7^,8 In disease surveillance, their integration into wearable systems enables continuous, real-time tracking of biomarkers such as heart rate, blood oxygenation, and neural activity with unprecedented accuracy. Innovations such as stretchable skin-like patches and wireless epidermal oximeters exemplify how micro-scaled LEDs enhance data reliability while maintaining user comfort. In therapeutic applications, the synergy of micro-scaled LEDs with optogenetics has unlocked precise cellular manipulation, facilitating breakthroughs in cardiac regeneration, neural circuit modulation, and targeted cancer therapies.9^–11 Unlike traditional photodynamic therapy (PDT), micro-scaled LED-driven systems minimize thermal damage through localized, low-intensity illumination, expanding treatment options for deep-seated tumors and sensitive organs. Furthermore, in symptom rehabilitation, micro-scaled LEDs demonstrate transformative potential by restoring sensory functions and improving aesthetic outcomes. Optical cochlear implants (oCIs), for example, leverage high spectral selectivity to enhance hearing resolution, whereas flexible photostimulation devices promote tissue repair and hair regrowth through noninvasive light delivery.

This review systematically explores the interdisciplinary convergence of micro-scaled LED technology with biomedical engineering, highlighting its role in bridging gaps between clinical needs and technological capabilities. By examining recent innovations and challenges—such as biocompatibility, scalability, and integration with wireless systems—we aim to underscore how micro-scaled LEDs are redefining standards in precision medicine, patient-centric care, and sustainable healthcare delivery (Fig. 1).12^–14

In the field of disease monitoring, the integration of advanced technologies into everyday health care is becoming increasingly crucial as public awareness of health issues grows.15^–21 Although traditional wearable devices such as smartwatches and fitness trackers have made significant strides in monitoring biological signals, their limitations in accurately capturing physiological data due to a lack of skin conformity have prompted the need for more sophisticated solutions. In this case, micro-scaled LED technology has emerged as a transformative force in the field of disease surveillance. Traditional wearable devices often use pre-strain bending structures to provide stretchability by pre-stretching flexible substrates to form wrinkle structures. However, wrinkles in high-density pixel arrays can cause adjacent pixels to overlap and fail to achieve a high-resolution display. At the same time, the traditional wearable device adopts serpentine metal interconnection, which generate curved serpentine wires to absorb mechanical strain, but the space utilization rate of this scheme is low, resulting in problems such as limited pixel density; In addition, AC-driven electroluminescent devices are used to solve the luminous needs, but they require >100V voltage or 1 kHz high-frequency drive, and it is difficult to achieve visual brightness outdoors in common scenarios of wearable devices, and the power consumption is relatively high. Another light-emitting solution is organic light-emitting diodes, but its mechanical stability is poor, and direct stretching can easily lead to problems such as electrode fracture or degradation of the light-emitting layer while facing packaging challenges. Moreover, the rigid micro-scaled-LED chip emits light independently, avoiding the pixel overlap problem of the pre-strain structure; the micro-scale chip size can achieve >500PPI (pixels per inch), which is better than the space limitation of serpentine interconnection. At the same time, GaN-based micro-LEDs are stretch-resistant and can be embedded in an elastic substrate with flexible transfer printing technology, which is more resistant to oxygen/moisture than organic LEDs (OLEDs), and the life is extended several times.

Lee et al.18 reported a new type of wearable health monitoring patch [skin-like health care patches (SHPs)] capable of providing real-time heart rate information. This SHP, which is 15μm thick, includes a stretchable micro-light-emitting diode (micro-scaled LEDs) display and a stretchable photoplethysmography (PPG) heart rate sensor, both mounted on a fully elastic substrate and capable of stable operation under 30% strain.22^–28 PPG signals are measured by a stretchable organic PPG sensor (top) and a conventional silicon chip-based PPG sensor and digital images of each sensor attached to skin, as shown in Fig. 2(a); the SHP contains a stretchable micro-scaled LED array with a resolution of 17 pixels by 7 pixels, capable of clearly displaying letters and numbers. Figure 2(b) shows the structure of the SHP processing module; the researchers mention that by reducing pixel size, there is potential to increase the display resolution to 200 PPI. In the heart rate monitoring sensor, light emitted by the micro-scaled LEDs is used to illuminate the skin, and as blood flows through the vessels, it causes changes in the reflection or absorption of light, which can be detected by the PPG sensor and used to calculate the heart rate. System block diagram of data transmission from the PPG sensor to a micro-scaled LED display is shown in Fig. 2(c). In this SHP, the micro-scaled LEDs are integrated on a stretchable elastic substrate and operate at a low power consumption, enabling the SHP to be powered by a thin, flexible 3.8 V lithium battery, with the entire system’s power consumption at 16.5 mW, making it energy-efficient and suitable for long-term wear. The PPG sensor in the SHP has a high signal-to-noise ratio of >21dB, comparable to commercial silicon-based PPG sensors, indicating that it can provide accurate heart rate measurements even during wrist movement. The SHP patch independently integrated on the human arm is shown in Fig. 2(d). The flexible micro-scaled LEDs in the SHP show comparable brightness and current efficiency after stretching as when it is not stretched, and even after repeated stretching (>1000 times), the brightness only slightly decreases, demonstrating its excellent optical stability. Meanwhile, the manufacturing process of the SHP involves layered deposition and photolithography techniques, which have the advantages of high reliability and scalability. In this case, the SHP has become an ideal wearable health device, capable of providing real-time, accurate health information without sacrificing performance while maintaining user comfort and privacy. In addition, Fig. 2(e) shows that the heart rate measured by the PPG sensor is displayed in real time on the green micro-scaled LED array.

Tissue oxygenation changes are highly related to physiological activities such as neural activity, tissue perfusion, tumor microenvironment, and wound healing, making it an important indicator of the operational status and functional integrity of tissues and organs. Blood oxygen saturation is typically indirectly calibrated based on the correlation between blood and tissue oxygen saturation. Jeong et al.29 reported a miniaturized, battery-free, and wirelessly usable pulse oximeter system. This device, characterized by its ultra-miniature, lightweight, and battery-free design, can establish a long-term interface on different surfaces with minimal risk of irritation or discomfort. The device integrates advanced optoelectronic functions for wireless capture and transmission of pulse oximetry, including quantitative information on blood oxygenation, heart rate, and heart rate variability.30^,31 The miniaturization of micro-scaled LEDs allows the entire oximeter device to be designed as lightweight and compact, making it easy to attach to various parts of the body, such as fingertips, nails, or earlobes. In addition, micro-scaled LEDs provide specific wavelengths of red and infrared light in the device, which are used to penetrate the skin and illuminate the blood; it should be noted that red and infrared light can be selectively absorbed by hemoglobin (Hb) and oxyhemoglobin (HbO2) due to their specific wavelengths. By emitting red and infrared light, micro-scaled LEDs help measure the difference in absorption of these two types of light by hemoglobin in different oxygenation states and the proportion of oxyhemoglobin in arterial blood. Moreover, the light emitted by micro-scaled LEDs is used for PPG measurements, and by detecting changes in light intensity caused by blood volume changes, micro-scaled LEDs help obtain information on heart rate and heart rate variability; this miniaturized pulse oximeter can provide a noninvasive, continuous health monitoring solution, offering more possibilities for long-term health monitoring. Kim et al.30 also developed a battery-free, stretchable, wearable miniaturized optoelectronic system for wireless optical characterization of the skin. The epidermal wireless oximeter is shown in Fig. 3(a). The system is designed for multiwavelength optical characterization of the skin, and the working principle of the device is shown in Fig. 3(b), including heart rate monitoring, arterial blood flow dynamics, tissue oxygenation, ultraviolet dose measurement, and four-color skin spectral assessment. By integrating time-multiplexed micro-scaled LEDs and photodetectors, the system can perform precise optical measurements to diagnose peripheral vascular diseases, assess skin color changes, or detect environmental parameters. Micro-scaled LEDs, as small and low-power light sources, help maintain the compactness and lightness of the system. The system uses micro-scaled LEDs of different colors, which could provide multiwavelength light sources for measuring skin optical characteristics. In addition, infrared micro-scaled LEDs are used for heart rate measurement by detecting changes in light intensity caused by blood volume changes due to heartbeats.33^,34 Moreover, red and infrared LEDs are used together to calculate the concentration changes of oxyhemoglobin and deoxyhemoglobin in tissues by comparing the reflection or transmission of light at different wavelengths; images of the device operating during activation of the red LED (top) and the infrared LED (bottom) are shown in Fig. 3(c), and the image of the device mounted on the forearm is shown in Fig. 3(d). The system can be equipped with special materials that are activated by the light emitted by micro-scaled LEDs to measure the exposure dose of ultraviolet rays; by illuminating objects with light from different colored LEDs and measuring the reflected or transmitted light, the color characteristics of the object can be determined. This system provides a wireless and portable health monitoring experience, enabling real-time, accurate, and comprehensive monitoring of physiological parameters, highly integrating the comfort, convenience, and functionality required for health monitoring systems, and offering new possibilities for personal health management. The functional demonstration of the system and the comparison with the measured values of commercial oximeters are shown in Figs. 3(e)–3(g).

The ability to record neural activity in behaving mammals could greatly expand our understanding of brain function. Some of the most sophisticated existing methods use light delivered through implanted optical fiber cables to optically excite genetically encoded calcium indicators and record the resulting fluorescence changes; these methods are physically limited by the size, mass, and volume of the cables and associated equipment, complicating the study of natural behaviors. To investigate the optically recording dynamics of neurons in freely moving animals, Lu et al.35 proposed a wireless, injectable fluorophotometer, which includes a micro-scaled LED and an associated photodetector (μ-IPD). The schematic exploded-view illustration of a wireless, injectable, ultrathin photometry probe is shown in Fig. 4(a). Figure 4(b) shows the magnified colorized SEM image of the tip. In addition, the schematic illustration of a GaAs μ-IPD is shown in Fig. 4(c), and the schematic exploded-view illustration of a transponder is shown in Fig. 4(d). It should be noted that these devices are placed on a thin, narrow, flexible polyimide (PI) substrate, and a metal film defined by photolithographic techniques serves as an electrical interconnect; the entire system is encapsulated by a polydimethylsiloxane (PDMS) coating; thus, it is suitable for injection deep into the brain of interest to detect Ca2+ changes related to cellular activity.31^,36 In in vivo studies of freely moving animals, this technology allows for high-fidelity recording of calcium fluorescence in the deep brain, with measurement characteristics that match or exceed those of fiber optic-based photometers. The wireless detachable transponder on the fingertip and its working images are shown in Figs. 4(e)–4(f); it should be noted that this technology has potential broad applications in optically recording the dynamics of neurons in freely moving animals. The image of a freely moving mouse with a photometry system is shown in Fig. 4(g). This system operates most effectively in line-of-sight mode but can also be transmitted indirectly via reflection from surrounding objects. The wireless photometry technology eliminates all external connecting wires and fibers, bypassing the bulky optical instruments of traditional fiber photometers, allowing simultaneous recording of signals from multiple freely moving animals without the risk of entanglement or the animal manipulating connecting wires. Implantable photometry can detect transient calcium ion changes in active neurons of the mouse brain’s basolateral amygdala (BLA); the working principle of the system is shown in Fig. 4(h), which demonstrates the ability to monitor the neural activity of freely moving animals. This micro-scaled LED-based implantable excitation light source, in collaboration with photodetectors used to measure transmission, reflection, and emission, promotes the development of minimally invasive photometers, which can be applied to pulse oximeters, pH, and carbon dioxide sensors, among other applications.

Micro-scaled LEDs have transformed wearable disease surveillance by overcoming limitations of conventional devices through superior skin conformity, resolution, and energy efficiency. These LEDs enable ultra-thin, stretchable health patches, such as the 17pixel×7pixel array displaying real-time heart rate that maintain optical stability under 30% strain and after 1000+ mechanical cycles. Beyond wearables, micro-scaled LEDs facilitate wireless oximeters for blood oxygenation tracking and implantable neural monitors for deep-tissue activity recording, establishing continuous, clinical-grade health monitoring in daily life despite ongoing challenges in biocompatibility and scalable manufacturing.

In the field of disease treatment, the advent of micro-scaled LED technology has opened new horizons for medical innovation. Optogenetic stimulation, a method that combines genetic engineering with light control technology, has emerged as a powerful tool for precisely controlling cellular activity within living organisms. By introducing genes of specific photosensitive proteins [e.g., Channelrhodopsin-2 (ChR2)] into target cells, these proteins can alter ion channel states under illumination, leading to depolarization or hyperpolarization of the cell membrane. This precise control allows for targeted activation or silencing of specific neurons, offering unparalleled spatiotemporal precision. For the advantages of compact size, low energy consumption, and ability to provide specific wavelengths of light, micro-scaled LEDs have become integral to the advancement of optogenetic stimulation.

Myocardial infarction (MI) and other heart diseases lead to the loss of cardiomyocytes (CMs), causing adverse myocardial remodeling and deterioration of heart function. Therefore, finding effective methods to promote myocardial regeneration is crucial for restoring heart function. Optogenetics introduces photosensitive proteins such as Channelrhodopsin-2 (ChR2) into target cells genetically and activates these cells under appropriate wavelength illumination; this technique could offer high spatial and temporal resolution along with cell type specificity; thus, it could be used to silence or enhance the activity of specific neurons. Through optogenetic stimulation, cardiac nerves can be selectively activated, potentially promoting the proliferation of CMs and myocardial regeneration. Philipp et al.37 proposed a novel wireless, battery-free, fully implantable multimodal and multisite pacemaker for small animal models. This pacemaker, composed of energy-harvesting and control devices, stimulation electrodes, micro-scaled LEDs, antennas, and mechanical structures, weighs only 110 milligrams and is small enough for full subcutaneous implantation in small animal models without causing excessive burden, and this system has shown good long-term stability in both ex vivo and in vivo studies, with the ability to withstand over 200,000 cycles of multidirectional strain without reducing electrical or optical performance. In this study, the animal’s weight initially decreased after the implantation of the pacemaker but quickly returned to normal and increased over time, indicating that the animal adapted well to the implanted pacemaker without severe rejection reactions or other complications. In addition, researchers have conducted in vitro experiments using the pacemaker to electrically stimulate hearts expressing ChR2 and observed a significant increase in heart contraction frequency, and the ECG recording results showed that the device could effectively drive cardiac rhythm.38 In addition, it should be noted that the small size of micro-scaled LEDs ensures that the heat generated is controlled within a safe range, avoiding thermal damage to surrounding tissues. By controlling the illumination intensity, frequency, and duration of micro-scaled LEDs, researchers could precisely control the pacing rate and mode of the heart. The use of micro-scaled LEDs also allows for multimodal pacing, combining electrical stimulation with optogenetic stimulation, providing new tools for studying cardiac electrophysiology and the pathogenesis of heart disease. Yuan et al.39 also proposed a method to improve cardiac regeneration after myocardial infarction by optogenetically stimulating the cardiac vagus nerve, using an adeno-associated virus (AAV) as the vector to deliver the photosensitive protein ChR2 to the left cervical ganglion of the heart; the researchers were able to use micro-scaled LEDs emitting a specific wavelength of light (blue light at 470 nm in this study) to selectively activate the cardiac vagus nerve. After optogenetic stimulation of the cardiac vagus nerve, the study found a significant increase in the proliferative capacity of CMs. An optogenetic stimulation of the cardiac vagus nerve further activated the IL-10/STAT3 signaling pathway, which helps promote the polarization of cardiac macrophages to the M2 type.40^–42 M2 macrophages have anti-inflammatory and tissue repair-promoting effects, which are crucial for the process of cardiac regeneration and repair. The study results showed that optogenetic stimulation not only promoted the proliferation of CMs but also improved heart function after myocardial infarction. By evaluating cardiac ejection fraction (EF) and other cardiac function parameters, researchers found that optogenetic stimulation helps maintain heart function and reduce ventricular remodeling. In this study, micro-scaled LEDs provided specific wavelengths of light (blue light at 470 nm in this study), which are necessary to activate ChR2-expressing cardiac vagal neurons that have been genetically modified; the illumination provided by micro-scaled LEDs can precisely control the start and end of stimulation, as well as the duration and frequency, thus achieving precise spatiotemporal regulation of cardiac vagal nerve activity; by changing the parameters of micro-scaled LEDs illumination (e.g., power, frequency, and pulse width), researchers can assess changes in cardiac function under different lighting conditions, such as minor changes in heart rate and blood pressure; the illumination from micro-scaled LEDs promotes the proliferation, dedifferentiation, and angiogenesis of CMs through the optogenetic mechanism, which are key processes for repair after heart damage; micro-scaled LEDs, with their miniaturized characteristics, facilitate implantation and fixation, making long-term and stable optogenetic stimulation in animal models possible. In this case, optogenetic stimulation based on micro-scaled LEDs could serve as an effective tool to activate specific neural pathways and provides new strategies for cardiac regeneration and repair; these applications demonstrate that micro-scaled LEDs have broad application prospects for the treatment of heart disease.

To promote the application of optogenetics in fundamental neuroscience research and facilitate its earlier clinical application, Ji et al.42 proposed a wireless optogenetic system for controlling the stimulation patterns and temperature of micro-scaled LEDs; the structure diagram of this system is shown in Fig. 5(a). This system employs wireless control, utilizing near-field magnetic coupling for energy and data transmission, eliminating the need for physical connections. In addition, this system combines the advantages of micro-scaled LED miniaturization, ease of implantation, and capability for brain stimulation and neural regulation, and the structure of the light source is shown in Fig. 5(b), enabling effective neural stimulation within a precisely controlled temperature range for neuromodulation of living organisms. In addition, by adjusting the light intensity, frequency, and duration of the micro-scaled LEDs, various modes of light stimulation can be achieved. Meanwhile, the localized light stimulation and thermal effects of micro-scaled LEDs can be effectively controlled, with the device’s temperature changes maintained within a range of 1°C to 2°C during light stimulation, ensuring good thermal stability and safety without causing overheating or other damage to biological tissues. In this case, micro-scaled LED optogenetic devices have presented the advantages of precise light stimulation, high safety, and high efficacy during the treatment process, offering a new tool and method for neuroscience research and the clinical application of optogenetic stimulation.

As a cutting-edge biotechnology, optogenetic stimulation involves the introduction of light-sensitive proteins into cells to precisely control cellular activity using specific wavelengths of light. Micro-scaled LEDs with small size, low energy consumption, high power, rapid light pulse response, and high biocompatibility hold a significant position in the research and clinical application of optogenetic stimulation technology. They have important applications in various fields such as cardiac regeneration and repair, hearing recovery, hair growth stimulation, and neuroscience research. The advantages of micro-scaled LEDs, such as their miniaturization for easy implantation, highlight an output with superior energy efficiency and excellent mechanical and thermal stability, making them an ideal choice for optogenetic research. Furthermore, they provide innovative solutions for clinical treatments and are expected to play an increasingly vital role in the future of biomedicine. In addition, optogenetic stimulation using micro-scaled LEDs has presented remarkable potential in terms of safety, efficacy, and multifunctionality, offering new perspectives and methods for the treatment of various diseases.

PDT is a method that uses drugs (photosensitizers) and specific wavelengths of light to treat diseases. This therapy is commonly used for the treatment of cancer and certain non-cancerous conditions, such as certain types of skin lesions, age-related macular degeneration (AMD), and port-wine stains, among others.44^–50 It offers advantages such as selectivity, minimal invasiveness, repeatability, and fewer side effects. However, traditional PDT has some issues, such as insufficient light intensity and potential thermal tissue damage. To enhance the reliability and safety of PDT, Yamagishi, Kento et al.44 proposed a new treatment method, modulated photodynamic therapy (mPDT), which uses lower-intensity light and extends the illumination time to reduce the risk of thermal damage. To achieve this goal, researchers developed an implantable, wirelessly powered mPDT system capable of stably attaching to the surface of internal tissues in animals to provide continuous localized illumination of the target tumor. They designed a micro-scaled LED based on near-field communication (NFC) for wireless power supply and light control and created a bioadhesive, stretchable nanosheet using PDMS nanosheets and a polydopamine modification layer for stable device attachment; the tissue-adhesive optoelectronic device allows for suture-free device fixation, permitting continuous phototherapeutic treatment for up to ten days. In animal models, the mPDT system demonstrated significant anti-tumor effects, using ∼1000 times less light intensity than conventional PDT, greatly reducing the risk of thermal damage. By altering the LED wavelength, the study found that green light (530 nm) had a stronger anti-tumor effect than red light (630 nm), likely related to the photosensitizer’s absorption characteristics of different wavelengths of light; this research provides a new treatment strategy suitable for undetectable micro-tumors or deep-seated lesions that standard phototherapy cannot reach. The mPDT system is minimally invasive, highly secure, and hopefully being used to treat tumors in fragile or sensitive organs such as the brain and pancreas. The development of this wirelessly implantable mPDT device offers a new, minimally invasive, highly effective, and safe method for cancer treatment, promising to improve patient outcomes and quality of life. Traditional PDT uses intense visible light, but the limited penetration depth of light in biological tissue leads to immune suppression in tumor tissue. Choi et al.50 proposed an implantable micro-scaled LED, consisting of one to four 10μm micro-scaled LEDs stacked on a needle-like photonic device, which can be directly implanted into the core of tumor tissue; the device structure is shown in Fig. 6(a). It can activate photosensitizers deep within the body with mild visible light, enhancing anti-tumor immunity. As shown in Fig. 6(b), the micro-scaled LED device can be directly implanted into the core of tumor tissue, allowing light to be effectively activated deep within tumor tissue, thus addressing the issue of traditional PDT methods where light cannot penetrate deep tissue. As shown in Fig. 6(c), with appropriate light intensity and duration, the micro-scaled LEDs could induce tumor cells to undergo immunogenic cell death (ICD), a form of cell death that activates an anti-tumor immune response. In addition, the micro-scaled LEDs could promote the maturation of dendritic cells (DCs) and the activation of T cells by inducing ICD, thereby enhancing anti-tumor immunity. In addition, when micro-scaled LED-guided PDT is combined with immune checkpoint blockade, it can significantly improve treatment effects, achieve complete tumor regression, and help establish immune memory to prevent tumor recurrence, offering new possibilities for cancer treatment.45^–50

Diabetic retinopathy is the most common cause of blindness among adults, and current treatment methods include laser therapy, intravitreal injections, and ocular surgery. However, these methods are highly invasive and cannot fully restore vision. Lee et al.19 developed a noninvasive, intelligent, wireless far red/near-infrared (far red/near-infrared, NIR) light-emitting contact lens for the repeated treatment of diabetic retinopathy, significantly improving patient compliance. After designing a micro-scaled LED integrated with an application-specific integrated circuit (ASIC) chip, wireless power supply, and communication system on a polyethylene terephthalate (PET) film, this device has been embedded in a silicone hydrogel contact lens through heat crosslinking. The image of the smart LED contact lens and its fabrication procedures are shown in Figs. 7(a)–7(c). Using this device, researchers have conducted in vitro testing, which confirmed that the smart far red/NIR LED contact lens has a statistically significant reduction in the hyperpermeability of retinal vessels induced by diabetic retinopathy, and the image of the far red/NIR light irradiation to a rabbit eye to treat diabetic retinopathy is shown in Fig. 7(d). Furthermore, through 8 weeks of treatment with 120μW light exposure for 15 min three times a week, the smart micro-scaled LED contact lens significantly reduced the hyperpermeability of retinal vessels in a rabbit model of diabetic retinopathy and also analyzed the safety and feasibility of the LED contact lens treatment for diabetic retinopathy using histological analysis. This technology offers a new treatment method for diabetic retinopathy, characterized by its noninvasiveness, reusability, and long-term treatment potential, promising to improve patient treatment experience and outcomes; the schematic illustration of the diabetic retinopathy treatment using the smart LED contact lens is shown in Fig. 7(e). The development of the intelligent contact lens provides a new noninvasive solution for the treatment of diabetic retinopathy, and it is expected to play a significant role in the field of biomedicine.

In the application of disease treatment, micro-scaled LEDs enable minimally invasive precision interventions through optogenetic control and targeted phototherapy. Wireless, battery-free implants (e.g., 110-mg cardiac pacemakers) use micro-scaled LEDs for optogenetic stimulation of CMs, achieving precise spatiotemporal modulation of heart rhythm and promoting tissue regeneration via vagus nerve activation.51^,52 For oncology, implantable micro-scaled LED systems deliver mPDT with 1000× lower light intensity than conventional PDT, enabling localized tumor eradication in deep tissues while avoiding thermal damage; when combined with immunotherapy, they trigger immunogenic cell death and suppress recurrence. In ophthalmology, micro-scaled LED-integrated contact lenses provide noninvasive, wireless far-red/NIR phototherapy for diabetic retinopathy, reducing retinal hyperpermeability at 120μW exposure with no tissue toxicity. These advancements—powered by micro-scaled LEDs’ spectral precision, miniaturization, and thermal stability (≤2°C fluctuation).53 In addition, this technology has redefined the precision medicine for cardiac, neural, and oncological disorders.

In the realm of symptom improvement for various medical conditions, micro-scaled LEDs have also emerged as a promising solution, offering innovative approaches to enhance patient outcomes.54^–57 Traditional electronic cochlear implants (eCIs) partially restore hearing by electrically stimulating the auditory nerve; however, the diffusion of electrical current around the electrodes limits spectral selectivity, making it difficult to discern speech, especially in the presence of background noise. Dieter et al.21 proposed an optogenetic method to overcome this limitation by employing viral-mediated optogenetic manipulation to render cochlear spiral ganglion neurons (SGNs) sensitive to light, followed by optical stimulation using micro-scaled LEDs. In addition, they have designed a multichannel oCI based on 16 miniaturized thin-film micro-scaled LEDs, which offer high spectral selectivity and moderate power requirements. As shown in Fig. 8(a), by conducting acute multichannel oCI stimulation experiments on adult Mongolian gerbils, optically evoked auditory brainstem response could be found in an AAV-CatCh-injected gerbil in response to a 1 ms laser pulse of ∼35mW; these results [as shown in Figs. 8(b)–8(d)] indicated that micro-scaled LEDs could activate the auditory pathway with high spectral selectivity, and optogenetic stimulation could still activate the auditory nerve even under conditions of deafness. Compared with the potentially damaging electrical stimulation of traditional cochlear implants, micro-scaled LEDs could also provide a noninvasive optical stimulation method that can precisely activate the optogenetically modified auditory nerve cells. Unlike the spectral selectivity limitations caused by electrical current diffusion in eCI, micro-scaled LEDs could offer higher spectral selectivity, thereby enhancing the resolution of sound encoding. In terms of precise control of stimulation, the micro-scaled LED beam can be accurately confined to a specific spatial range, achieving localized activation within the cochlea and avoiding unnecessary side effects. In addition, it should be noted that the oCI used in the study has 16 individually addressable micro-scaled LEDs, allowing for multichannel stimulation of the auditory nerve and simulating the complex sound processing of the natural auditory system, and the micro-scaled LED morphology in oCI is shown in Figs. 8(e)–8(g). Micro-scaled LEDs also have the advantage of miniaturization and easy integration into the oCI to reduce spatial constraints, and in this device, they are integrated into highly biocompatible medical-grade silicone, reducing the immune response and tissue rejection caused by the implanted device, the micro-scaled LED functional relationship between radiation power and driving current is shown in Fig. 8(h) and schematic diagram of ocI inserted into the cochlea through cochlear stoma is shown in Fig. 8(i), it should be noted that the micro-scaled LEDs in the device showed no significant performance differences after 10,000 bending/unbending cycles, demonstrating excellent mechanical reliability. In addition, a schematic diagram of 3D X-ray tomography reconstruction of 16-channel oCI implanted into the cochlea of gerbils through a round window is shown in Fig. 8(j); these results indicate that the micro-scaled LED-based oCI has higher spectral selectivity in activating the auditory nerve compared with clinically used cochlear implants. In a word, the combination of optogenetic technology and microsystems engineering offers hope for improving the quality of artificial hearing and providing new treatment strategies for patients with sensorineural deafness.

In addition to their applications in auditory nerve stimulation, micro-scaled LED-based optogenetic devices have also shown promise in the field of hair growth. Alopecia, or hair loss, is a widespread issue that can lead to aesthetic concerns, decreased self-esteem, and social anxiety. Existing methods for hair regrowth using laser skin stimulation are often limited by high energy consumption, bulky equipment, and restricted daily use. To overcome these limitations, Lee et al.20 proposed a wearable photo-medical device using flexible micro-scaled LEDs for hair growth applications. These flexible micro-scaled LEDs exhibit high optical output power (∼30mW/mm2) and low forward voltage (∼2.8V), providing sufficient photic stimulation for hair growth while maintaining high energy efficiency. The conceptual illustration of trichogenic photostimulation via monolithic red micro-scaled LEDs is shown in Fig. 9(a). The micro-scaled LEDs are manufactured through a simple monolithic process, with a thickness of only 20μm, making them extremely thin and lightweight. In addition, the micro-scaled LEDs can conform to the surface of human skin and maintain stable light emission even during activities such as wrist bending, demonstrating excellent wearability and adaptability. In addition, for the thermal stability of micro-scaled LEDs using the finite element method (FEM): under a 10 mA current injection and the bent conditions, the maximum temperature of the micro-scaled LEDs is estimated to be only around 350 K, indicating that the device will not cause skin burns or damage during operation. After undergoing 10,000 bending/unbending cycles, the forward voltage of the flexible micro-scaled LEDs increased by only 1.1 V, and the optical output decreased by only 1.68mW/mm2, showing excellent mechanical reliability suitable for long-term use. In mouse experiments, micro-scaled LEDs provided a specific wavelength of red light (∼650nm), which can penetrate the skin tissue to a depth of ∼2mm to stimulate hair follicles located beneath the dermis, a schematic diagram of the relationship between hair regeneration area and skin stimulation days is shown in Fig. 9(b); in addition, it should be noted that the red light is believed to accelerate the proliferation of hair follicle cells and the hair growth cycle, particularly promoting the entry into the anagen phase. Periodic light exposure using micro-scaled LEDs has been shown to promote hair growth. Compared with the positive control group treated with minoxidil (MNX), the group treated with micro-scaled LEDs showed a wider area of hair regrowth and longer hair strands. The hair image of mice after 20 days of experiment and the comparison are shown in Fig. 9(c). Through histological and immunofluorescence analysis, researchers observed an increase in the proliferation of hair stem cells in the skin tissue of mice treated with micro-scaled LEDs, as well as the activation of the Wnt/β-catenin signaling pathway, which is closely related to hair regeneration; the comparison results are shown in Fig. 9(d). This micro-scaled LED-based photo-medical device offers a new, safe, and effective treatment option for patients with alopecia, providing a new tool for clinical research and practical therapeutic applications. Moreover, this device has the potential for application in other areas, such as wound healing, acne treatment, and skin whitening.

Park et al.58 proposed a wireless, implantable miniaturized phototherapy device for the repair of oral inflammation. This device can be implanted in the oral cavity for an extended period to treat oral inflammation such as periodontitis. The device uses a specific wavelength of near-infrared light (808 nm), which has a significant effect on promoting the repair of alveolar wound tissue. Parameters such as the radiation dose and optical power density of phototherapy directly affect the therapeutic effect. The researchers designed a near-field wireless power supply system based on magnetic resonance coupling, optimizing coupling parameters (e.g., coupling mode, resonance mode, vibration frequency, and coupling coefficient) and coil design (e.g., the quality factor of the coil) to ensure that the device receives sufficient energy. The micro-scaled LED chip, integrated with a wireless receiving coil, forms a complete implantable device that is driven by an external AC power source, achieving wireless energy transfer and phototherapy effects. By adjusting the voltage and frequency of the external power source, as well as the distance between the coils, the energy input, and output power density of the device can be controlled, thereby regulating the intensity and effect of the phototherapy. The researchers tested the optical, electrical, RF, and thermal performance of the device in vitro simulation experiments to ensure the stability and safety of the device in practical applications. The device can provide sufficient optical power to treat damaged tissue while ensuring that the device itself does not overheat and burn gum tissue within the working cycle (2 min). The wireless, implantable miniaturized phototherapy device showed a relatively stable trend in vitro tests, proving its potential in the treatment of oral inflammation. This wireless, implantable miniaturized phototherapy device provides a new type of oral inflammation treatment method through precisely controlled phototherapy mechanisms, characterized by simplicity of operation, significant therapeutic effects, and high safety.

Micro-scaled LEDs have also attracted great attention in the fields of brain–computer interface (BCI).59^,60 For example, Gu et al.60 proposed a photogenetic device, which successfully integrates high-density micro-LED arrays with electrocorticogram (ECoG) electrodes; the fabricated micro-LED arrays are shown in Fig. 10(a). As the direct measurement of light intensity is very challenging, raytracing simulations were employed as shown in Fig. 10(b) to estimate light penetration through the brain; the simulation results show that the light intensity decreases significantly with increasing brain depth. In addition, the light penetration of micro-LEDs was analyzed experimentally using brain tissue; Fig. 10(c) shows the emission spectra of micro-LED arrays after passing through brain slices from 0 to 200μm, revealing a decrease in the spectrum intensity with increasing brain thickness. Moreover, Fig. 10(d) shows the results of thermal measurement using an infrared thermal camera equipped with a macro lens (HM-TP9X-640HC, HIKMICRO Co., Ltd.). In vivo acute animal experiments were performed to validate the optical stimulation and recording functionality of the optogenetic device. Neurons of Sprague–Dawley rats were transfected with ChR2 to enable light sensitivity. Figure 10(e) shows an illustration of the device attached to the cortical surface of the rat, with insets showing images with and without optical stimulation from the embedded micro-LED arrays. The representative local field potentials (LFPs) recorded by one column of channels are depicted in Fig. 10(f), demonstrating the effective neural activity recording capabilities of the microelectrodes. Figure 10(g) illustrates the ECOG signals captured from channel #42 (chan42) under three distinct conditions. Initially, recordings were conducted during optical stimulation in a PBS solution (LED-ON, in vitro), revealing only transient artifacts induced by the pulses. In vivo recordings without light stimulation (LED-OFF) exhibited suppressed neural activity due to anesthesia. However, when the brain was stimulated with a 0.1 Hz square wave at 2.8 V (50 ms duration), the neural activities of the rat were significantly activated.

In addition, Wang et al.59 adopted LEDs to generate high-frequency (40 Hz) coded modulation cVEP. Compared with traditional computer displays (the maximum refresh rate only supports 30 Hz stimulation), high-frequency stimulation can improve the information transfer rate (ITR) and break through the performance bottleneck of the existing cVEP paradigm. cVEP is the natural response of the brain to the visual stimulation of a specific coding sequence,3^,24 which can be generated when the user gazes at the coding sequence, flashing the light source. As a stimulus-driven BCI, the cVEP paradigm does not require long-term training compared with the imagination-driven paradigm. This work first combined green–blue dual-color stimulation with cVEP-BCI to verify the feasibility of LED hardware instead of monitors, reduce the risk of PSE through chroma modulation, and provide a safe interaction program for people susceptible to epilepsy (e.g., ALS patients).

Micro-scaled LEDs advance symptom rehabilitation by enabling noninvasive functional restoration and aesthetic recovery across sensory and dermatological applications. In auditory restoration, 16-channel oCIs leverage micro-LEDs’ high spectral selectivity to activate optogenetically modified spiral ganglion neurons, achieving superior sound resolution over traditional electrical implants while maintaining biocompatibility under mechanical stress. For dermatological conditions, flexible micro-LED patches deliver targeted phototherapy-red light penetrates 2 mm to stimulate hair follicles via Wnt/β-catenin signaling, demonstrating regrowth efficacy exceeding minoxidil in murine models, whereas wireless implantable NIR devices promote oral tissue repair in periodontitis through controlled photobiomodulation. Integrated into brain–computer interfaces, micro-LED arrays further enable high-density optogenetic neural stimulation for sensory-motor rehabilitation, collectively establishing micro-LEDs as versatile tools for minimally invasive, patient-centric symptom management.61^–64

The rapid evolution of micro-scaled LEDs technology has positioned it as a cornerstone of innovation in biomedical research, bridging the gap between advanced engineering and clinical practicality. Unlike conventional methodologies constrained by bulk, invasiveness, or limited precision, micro-scaled LEDs redefine therapeutic and diagnostic paradigms through their unique amalgamation of miniaturization, energy efficiency, and spectral versatility. This review underscores how the intrinsic properties of micro-scaled LEDs, such as high spatial resolution, biocompatibility, and adaptability to flexible substrates, address the longstanding challenges across medical disciplines.

In disease surveillance, the shift from intermittent clinical measurements to continuous, patient-friendly monitoring exemplifies the technology’s capacity to democratize healthcare access. Wearable systems empowered by micro-scaled LEDs not only enhance diagnostic accuracy but also empower individuals to proactively manage chronic conditions. For therapeutic interventions, the integration of micro-scaled LEDs with optogenetics and photodynamic mechanisms has enabled unprecedented control over cellular processes, from neuronal activation to tumor eradication, while minimizing collateral damage. Similarly, in symptom rehabilitation, devices based on micro-scaled LEDs such as oCIs and photostimulation patches highlight the potential to restore functionality and aesthetics through minimally invasive, patient-centric designs. In addition, the innovative application of micro-scaled LEDs in the field of BICs provides an important technical reserve for the next generation of high-performance BICs.

However, the translation of micro-scaled LED innovations into mainstream clinical practice faces hurdles. Long-term biocompatibility, thermal management in implantable systems, and scalability of fabrication processes remain critical barriers. Furthermore, interdisciplinary collaboration—spanning materials science, bioengineering, and clinical medicine—is essential to optimize device performance and validate safety in diverse physiological environments. Future advancements may focus on hybrid systems combining micro-scaled LEDs with artificial-intelligence-driven analytics or biodegradable materials to further enhance precision and sustainability.

Ultimately, the trajectory of micro-scaled LED technology in biomedicine hinges on balancing technical refinement with ethical and economic considerations. As these challenges are addressed, micro-scaled LEDs hold the promise of not only augmenting existing therapies but also pioneering entirely new modalities of care, ultimately fostering a future where medical interventions are as seamless as they are transformative.

Acknowledgment. This work was supported by the 2024 Key Technological Innovation and Industrialization Project of Fujian Province (Grant No. 2024G021), the National Natural Science Foundation of China (Grant No. 62274138), the Natural Science Foundation of Fujian Province of China (Grant No. 2023J06012), the Science and Technology Plan Project in Fujian Province of China (Grant No. 2021H0011), the Fundamental Research Funds for the Central Universities (Grant No. 20720230029), the Compound Semiconductor Technology Collaborative Innovation Platform Project of FuXiaQuan National Independent Innovation Demonstration Zone (Grant No. 3502ZCQXT2022005). The authors would like to thank Prof. Tiebin Yan of Sun Yat-Sen Memorial Hospital for his helpful discussion.

He Huang received his BS degree in applied physics from the Donghua University in 2023, and he has been an MS candidate at the Xiamen University since 2023.

Longting He received his BS degree in rehabilitation therapy from the Fujian Medical University in 2018, and he is currently employed at the Xiamen Fifth Hospital.

Shirui Cai received his BS degree in electronic information science and technology from the Nanjing Agricultural University in 2023, and he has been an MS candidate at the Xiamen University since 2023.

Yuxuan Liu received his BS degree in applied physics from the Donghua University in 2023, and he has been an MS candidate at the Xiamen University since 2023.

Xiaokuo He received his BS degree in clinical medicine from the Hubei University of Medicine in 1998, his MS degree in rehabilitation medicine and physiotherapy from the Huazhong University of Science and Technology in 2004, and his PhD in rehabilitation medicine and physiotherapy from the Sun Yat-sen University in 2013. He is currently the director of the Rehabilitation Medicine Center at the Xiamen Fifth Hospital, holding the professional title of Chief Physician. His research focuses on fundamental and clinical studies in neurological rehabilitation.

Xinxin Zheng graduated from the Chongqing Medical College, and she is currently employed at the Xiamen Fifth Hospital.

Shouqiang Lai received his BS degree in optoelectronic information science and engineering from the Fuzhou University in 2018, and he has been a PhD candidate at the Xiamen University since 2021.

Tingzhu Wu received his BS degree in electronic science and technology from the Zhejiang University in 2007, his MS degree in integrated circuit design engineering from the Hong Kong University of Science and Technology in 2008, and his PhD in radio physics from the Xiamen University in 2017. From 2017 to 2020, he was engaged in postdoctoral research at the Xiamen University, during which he went to the Taiwan Chiao Tung University as a visiting scholar. He mainly engaged in micro-LED display technology, LED lighting, and display research.

Zhong Chen received his BS and MS degrees in radio physics from the Xiamen University and his PhD in physical chemistry from the Xiamen University in 1992. In 2000, he was promoted to a professor in the Department of Chemistry, Xiamen University. In early 2003, he served as a visiting professor in the Department of Chemistry, Taiwan University. Since 2019, he has been the dean of the School of Electronic Science and Technology, Xiamen University. His research interests include magnetic resonance and LED technology and their applications.