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
Advanced Photonics Nexus, Volume. 4, Issue 5, 054001(2025)
Recent developments of micro-scaled LED-based technologies and mechanisms in the fields of healthcare
Micro-scaled light-emitting diode (LED) technology has emerged as a transformative tool in biomedical applications, offering innovative solutions across disease surveillance, treatment, and symptom rehabilitation. In disease surveillance, micro-scaled LEDs enable real-time, noninvasive monitoring of physiological parameters through wearable devices, such as skin-like health patches and wireless pulse oximeters; these systems leverage the miniaturization, low power consumption, and high precision of micro-scaled LEDs to track heart rate, blood oxygenation, and neural activity with exceptional accuracy. For disease treatment, micro-scaled LEDs play a pivotal role in optogenetic stimulation and phototherapy. By delivering specific light wavelengths, they enable precise cellular control for cardiac regeneration, neural modulation, and targeted cancer therapies, such as photodynamic therapy with reduced invasiveness. In addition, wireless micro-scaled LED systems facilitate localized and sustained treatments for conditions such as diabetic retinopathy. For symptom rehabilitation, micro-scaled LED-based devices enhance functional and aesthetic outcomes, exemplified by optical cochlear implants for high-resolution hearing restoration and flexible photostimulation patches for hair regrowth. The performance of micro-scale LEDs also brings new possibilities to the field of brain–computer interface. These applications highlight the versatility of micro-scaled LEDs in improving patient quality of life through minimally invasive, energy-efficient, and biocompatible solutions. Although there are still challenges in long-term stability and scalability, the integration of micro-scaled LEDs with advanced biomedical technologies promises to redefine personalized healthcare and therapeutic efficacy.
1 Introduction
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
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
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
Sign up for Advanced Photonics Nexus TOC Get the latest issue of Advanced Photonics delivered right to you!Sign up now
Figure 1.Advanced applications of micro-scaled LED-based technologies and mechanisms in the fields of healthcare. Figures reproduced with permission from Ref. 18, under a Creative Commons Attribution Noncommercial (CC-BY-NC) license; Ref. 19, under CC-BY license; and Ref. 20, under CC-BY license.
2 Application of Micro-Scaled LEDs in the Field of Disease Surveillance
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
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 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
Figure 2.Standalone skin-like SHP for real-time heart rate monitoring. (a) PPG signals measured by a stretchable organic PPG sensor (top) and a conventional silicon chip-based PPG sensor (SFH7060, OSRAM Opto Semiconductors Inc.; bottom) and digital images of each sensor attached to the skin. The silicon chip-based PPG sensor is fixed on the skin with adhesive tape. (b) Photograph of a processing module. The blue box (bottom) illustrates the integrated circuit components of the SHP: ① microcontroller, ② voltage regulators, ③ module switch, ④ boost converter, ⑤ analog front-end, and ⑥ battery connectors. (c) System block diagram of data transmission from the PPG sensor to a micro-scaled LED display. (d) Photographs of the fully integrated standalone SHP device attached to human skin with the red micro-scaled LED array in dynamic operation (letters “S A I T” are sequentially displayed and scrolled on the micro-scaled LED array). Inset: SHP on the skin with conformal contact. (e) Digital image of the SHP under operation. The heart rate measured by the PPG sensor is displayed in real time on the green micro-scaled LED array. Photo credit: Yeongjun Lee, SAIT. Figures reproduced with permission from Ref. 18, under CC-BY-NC license.
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 () 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).
Figure 3.Wireless epidermal optoelectronic system with two pulsed LEDs and a single photodetector to monitor peripheral vascular disease. (a) Image of an epidermal wireless oximeter that includes a red LED, an IR LED, a photodiode, and associated electronics all in a stretchable configuration mounted on a soft, black textile substrate coated with a low-modulus silicone elastomer. (b) Schematic illustration of the circuit of the device. An astable oscillator switches current between the two LEDs to allow time-multiplexed measurement of both wavelengths with a single photodetector. The R1C1 and R2C2 tanks set the frequency of the oscillator. GND, ground. (c) Images of the device operating during activation of the red LED (top) and the infrared LED (bottom). (d) Image of the device mounted on the forearm. Insert: schematic illustration of the operating principle. (e) Functional demonstration in a procedure that involves transient vein occlusion (gray box in the graph). An inflating cuff on the participant’s bicep temporarily occludes venous blood flow set to a pressure slightly below the arterial pressure (50 mmHg). (f) Magnified view of the red dashed box in (e). (g) and (h) Measurements obtained by a commercial oximeter and an epidermal device, simultaneously recorded from adjacent regions of the forearm. NIRS, NIR spectroscopy. Figures reproduced from Ref. 30, under CC-BY-NC license.
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 (-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 -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 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.
Figure 4.Miniaturized, ultrathin, lightweight wireless photometry systems for deep-brain Ca2+ measurements. (a) Schematic exploded-view illustration of a wireless, injectable, ultrathin photometry probe with a
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 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.
3 Application of Micro-Scaled LEDs in the Field of Disease Treatment
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
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.
Figure 5.System overall structure diagram: (a) wireless optogenetic micro-scaled LED array stimulation circuit; (b) wireless power supply circuit. Figures reproduced from Ref. 42, under CC-BY license.
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
Figure 6.Implantable micro-scale LED device (micro-scaled LEDs) guided PDT to potentiate antitumor immunity with mild visible light. (a) The micro-scaled LEDs are prepared by stacking micro-scale LED fabricated on a polyimide (PI) substrate and transferred onto an injection guide, which was designed as a needle-like structure with polysiloxane acrylate. (b) The micro-scaled LEDs are directly implanted into the core part of the tumor tissues, followed by irradiation with visible light. (c) The mechanism of micro-scaled LED-guided PDT in the tumor tissues depending on the optimal, less, or over light intensity. Under the optimal light intensity, the tumor cells release DAMPs through PDT-mediated ICD, thereby promoting DC maturation and T cell activation to inhibit the progression of primary and recurrent tumors by antitumor immunity. When over-light intensity is irradiated to tumor tissues, severe inflammatory responses are induced by necrotic cell death, which releases the immunosuppressive cytokine IL-10 and activates regulatory T cells, resulting in immunosuppression. In the case of tumor tissues irradiated with too low light intensity, a potent antitumor immunity is not induced owing to the insufficient ICD in tumor cells. Figures reproduced from Ref. 50, under CC-BY license.
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 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.
Figure 7.Schematic illustration for the preparation and phototherapy of a smart LED contact lens. (a) Photo image of a smart LED contact lens. (b) Photo image of wirelessly red, green, and blue (RGB) color lighting LED contact lenses. (c) Schematic illustration for the fabrication process of the smart LED contact lens: E-beam deposition of Cr/Au for thin film coating on the cleaned PET substrate, patterning by photolithography, ASIC chip bonding with a flip-chip bonder, LED bonding with a wire bonder, laser cutting of the unnecessary part of PET substrate, Parylene C coating for passivation, and lens fabrication by curing in the silicone elastomer solution. (d) Photo image of far red/NIR light irradiation to a rabbit eye to treat diabetic retinopathy. (e) Schematic illustration of the diabetic retinopathy treatment using a smart LED contact lens. Figures reproduced from Ref. 19, under CC-BY license.
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 exposure with no tissue toxicity. These advancements—powered by micro-scaled LEDs’ spectral precision, miniaturization, and thermal stability ( fluctuation).53 In addition, this technology has redefined the precision medicine for cardiac, neural, and oncological disorders.
4 Application of Micro-Scaled LEDs in the Improvement of Disease Symptoms
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
Figure 8.
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 () and low forward voltage (), 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 , 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 , showing excellent mechanical reliability suitable for long-term use. In mouse experiments, micro-scaled LEDs provided a specific wavelength of red light (), which can penetrate the skin tissue to a depth of 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 -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.
Figure 9.(a) Conceptual illustration of trichogenic photostimulation via monolithic red
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 , 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.
Figure 10.(a) MicroLED array-based optogenetics device. (b) LED illumination simulation under different voltages using the ray tracing software (TracePro), simulating the spread of light in the brain with 3 million rays. (c) Light intensities along the vertical direction of the microLED centerline under different voltages, extracted from simulation data. (d) Distribution of microLED temperature rise measured by the infrared thermal camera. (e) Illustration of the optogenetic device attached to the cortical surface of the rat. The insets show images with and without optical stimulation from the embedded microLEDs. (f) Representative LFPs recorded by one column of channels, demonstrating effective neural activity recording capabilities. (g) ECOG signals recorded from one channel under three different conditions: in vitro with optical stimulation, in vivo with light stimulation, and in vivo without light stimulation. Figures reproduced from Ref. 60 with permission, © 2024 ACS.
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 -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
5 Conclusion
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.
Acknowledgments
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.
[62] et alWireless implantable phototherapy device for oral inflammation repair, 2474-3747(2021).
Get Citation
Copy Citation Text
He Huang, Longting He, Shirui Cai, Yuxuan Liu, Xiaokuo He, Xinxin Zheng, Shouqiang Lai, Tingzhu Wu, Zhong Chen, "Recent developments of micro-scaled LED-based technologies and mechanisms in the fields of healthcare," Adv. Photon. Nexus 4, 054001 (2025)
Category: Reviews
Received: Jun. 14, 2025
Accepted: Jul. 29, 2025
Published Online: Sep. 4, 2025
The Author Email: Shouqiang Lai (laishouqiang@foxmail.com), Tingzhu Wu (wutingzhu@xmu.edu.cn), Zhong Chen (chenz@xmu.edu.cn)