To address the challenges of performance and applicability in LED phototherapy devices, researchers have introduced a variety of innovative strategies through material selection and process optimization. Significant progress has been made in areas such as soft substrates, soft active materials, soft emissive layers, soft encapsulations, and power supplies.
The soft substrate is critical for determining the mechanical properties of phototherapy devices and ensuring compatibility with target tissues (Fig. 4a). An ideal substrate, as summarized in the table shown in Fig. 4a, should have a lower Young's modulus than the target tissue while providing sufficient tensile strength, high-temperature resistance, chemical stability, and stretchability. Polyimide (PI) is well-suited for wearable and implantable devices due to its thermal and mechanical properties, while softer, biocompatible materials like Polydimethylsiloxane (PDMS), Thermoplastic Polyurethane (TPU), Styrene-Ethylene-Butylene-Styrene (SEBS), and Ecoflex are preferable for dynamic areas. Tailoring substrate selection to specific applications enables optimal adaptation to target regions. For example, wrapping the spinal cord for optogenetic therapies in paralysis treatment, conforming to the body surface for blue-light therapy in jaundice management, or adhering to the intestinal lining for red-light therapy applications (Fig. 4a).
In the fabrication of wearable or implantable phototherapy devices, soft active materials (Fig. 4b) should exhibit essential characteristics such as high electrical conductivity, stretchability, low cost, compatibility with diverse fabrication processes, biocompatibility, and durability. These requirements are designed to ensure that phototherapy devices maintain efficient optical power output to meet therapeutic needs while preserving stretchability.
Metal thin films are commonly used in device circuits due to their high conductivity and cost-effectiveness. They have been applied in optogenetic modulation for epilepsy, phototherapeutic repair of cerebral infarction, antimicrobial treatments for implant infections, and red-light therapy for hair loss. Structural optimization ensures their flexibility and mechanical stability. Current research mainly focuses on techniques such as serpentine patterns, island-bridge structures, or metal cracks to enhance their tensile strength. However, these approaches often significantly increase the device's volume, which hinders miniaturization. Therefore, intrinsically stretchable materials such as liquid metals and polymers are better suited for future phototherapy devices. For instance, liquid metal materials, celebrated for their self-healing properties and exceptional ductility, are especially well-suited for dynamic applications, such as treating arthritis, adapting to the beating surface of the heart, and addressing urinary dysfunction through optogenetic modulation in response to bladder pressure changes. Encapsulating liquid metals in elastomers can further improve their stretchability. Furthermore, the liquid metal's inherent chemical stability and the hermetic sealing design effectively address the challenges of oxidation, ensuring long-term performance and reliability in stretchable systems. Conductive polymers, which offer good stretchability and low cost, are another promising option. Although they are susceptible to water and oxygen degradation, surface molecular modifications can significantly enhance their durability, while maintaining good electrical conductivity (Fig. 4b). Many novel soft active materials can meet these requirements but are limited by their thermal tolerance, making them unsuitable for high-temperature processing. Consequently, the development of low-temperature fabrication techniques offers a pathway to expand the applications of these advanced materials. Cutting-edge processing methods currently include spin coating, 3D printing, screen printing, inkjet printing, dispensing printing, and photolithography (Fig. 4b).
The light sources used in flexible LED-based phototherapy devices can be classified into three main types: µLEDs, OLED, and QLEDs. µLEDs offer high light intensity ( ~ 1,000,000 nits), long lifespan ( ~ 100,000 h), and a narrow FWHM (15-20 nm), but have limitations in heat dissipation, flexibility, and light uniformity compared to OLED and QLED. OLED-based devices require further enhancement in brightness and resistance to oxygen and moisture, while QLEDs need to improve stability, ensuring no heavy metal incorporation (Table 2). To address these challenges, researchers have proposed various strategies.
In the field of soft emission components, µLEDs/Micro-LED have become a focal point due to their high brightness, dense emission, and exceptional precision, making them the ideal selection for phototherapy device (Fig. 4c, Table 2). The challenge of transferring µLEDs onto flexible substrates has been effectively resolved with advanced laser transfer technologies. With decreasing costs, flexible µLEDs show great promise as phototherapy light sources, particularly for complex surfaces like the face, intestines, brain, heart, and lungs.
At the same time, OLED materials, conferring flexibility, low-temperature fabrication, and uniform light emission (Table 2), are already being applied in areas such as diabetic management, hyperbilirubinemia treatment, hemodynamic monitoring, and neuroregulation. However, their limited lifespan under high-intensity illumination constrains their broader use in phototherapy devices. While photobiomodulation and metronomic photodynamic therapy (PDT) can achieve therapeutic effects at lower light intensities, simultaneous improvements in brightness and durability are essential to extend OLED applications to a wider range of therapies, including photodynamic and photothermal treatments. Encouragingly, advances in thin-film packaging technologies are now effectively addressing these issues. In parallel, new OLED optimization strategies, such as incorporating special solvents to dilute and reduce defects in the regions where electrons are captured within the OLED structure, along with the use of the double-sided polariton-enhanced Purcell effect to improve OLED stability, are further enhancing the light emission efficiency and lifespan of OLEDs (Fig. 4c). As detailed in Table 2, Red/Green (Phosphorescent) OLEDs exhibit lifespans exceeding ~100,000 h, while Blue OLEDs, especially the phosphorescent type, are showing ongoing improvements. Remarkably, researchers have also achieved major breakthroughs in the fabrication of intrinsically stretchable OLEDs, which currently represent the most stretchable light-emitting components developed to date.
QLEDs offer excellent flexibility, uniform surface emission, high light intensity ( > 300,000 nits), and narrow FWHM (20-30 nm) (Table 2). Current research focuses on developing biocompatible, heavy-metal-free (e.g., Cd-free) flexible QLEDs. However, their limited stability and short lifespan remain significant challenges for phototherapy, with only a few studies addressing these issues. New methods, such as electrically excited transient absorption (EETA), can effectively quantify the issues present in heavy-metal-free QLEDs. By optimizing the core-shell structure and surface passivation strategies, it is possible to further enhance the luminous efficiency and stability, ensuring the biological safety of QLEDs (Fig. 4c).
Encapsulation technologies also play a vital role in ensuring device stability. The ideal encapsulation should maintain the device's stretchability, lightweight nature, and durability (Fig. 4d). Hybrid organic/inorganic multilayer encapsulation combines the gas-barrier properties of inorganic layers with the flexibility of organic layers, providing stability for phototherapy devices in extreme environments such as fluid-filled cavities like the abdominal and thoracic cavities, intracranial regions, and even the gastrointestinal tract, while minimizing the risk of toxic substance leakage -- an essential consideration for implantable devices (Fig. 4d).
LED phototherapy devices must address the potential side effects of heat generation during use. The skin's outer layers, including the epidermis, dermis, and subcutaneous tissue, have low thermal conductivity (κ ≈ 0.3 W m K), posing challenges for heat management. An ideal design integrates flexible thermal materials, efficient heat dissipation structures, and effective heat transfer mechanisms (Fig. 4e). In phototherapy, an effective strategy for preventing thermal damage is to transmit the LED light source via optical fibers while keeping the heat-generating control units external. Metronomic PDT, using low-dose, extended-duration, high-frequency light, reduces local thermal load accumulation and provides an effective heat management solution. This approach offers a viable strategy for addressing heat dissipation in PBM, optogenetics, and blue light therapy. However, further studies are needed to assess its applicability across other phototherapy strategies. Additionally, advanced thermal management designs, such as polymer/boron nitride nanosheets and miniaturized microchannel heat sinks, offer potential solutions for enhancing heat dissipation in LED phototherapy devices (Fig. 4e).
The power supply for phototherapy devices (Fig. 4f) plays a pivotal role in determining their functionality and application potential. An ideal power source should combine high energy density, soft, biocompatibility, and durability to meet the diverse demands of wearable and implantable phototherapy systems. Recent innovations in power systems have been driven by soft batteries and wireless power transfer technologies, enabling both device miniaturization and extended operational lifespans. Soft batteries have progressed significantly, making it possible to integrate them into textiles for wearable phototherapy devices, such as LED therapy patches designed to treat skin conditions like acne, wounds, and psoriasis. Alternatively, they can be incorporated as miniaturized droplet or thin-film batteries in micro-sized phototherapy devices, allowing precise energy delivery for localized treatments. For implantable phototherapy devices, the choice of power source is dictated by the application. Solid-state batteries, with their ability to prevent toxic substance leakage, are better suited for long-term implantable systems. Wireless power transfer technologies, such as magnetic induction and triboelectric nanogenerators (TENGs), can harness kinetic energy from the human body to power implantable devices. These technologies expand the usability of phototherapy systems in scenarios requiring portability and frequent use. Additional methods, such as ultrasonic power, infrared functionality, and far-field communication (RF), present promising wireless energy options for implantable applications. These approaches are particularly advantageous for treatments requiring minimal device maintenance and long-term functionality. Despite these advances, phototherapy devices often demand substantial power for high-intensity light output, particularly in applications such as deep tissue treatment or PDT. In these cases, wireless power solutions alone are insufficient to sustain real-time energy needs and they must be paired with integrated batteries to provide reliable energy storage. The careful selection and integration of power systems, tailored to the specific clinical context, ensures that phototherapy devices achieve optimal performance across a wide range of medical applications.
In response to the challenges currently faced by LED-based phototherapy devices in clinical applications, as well as recent advancements in the field, we present a universal fabrication process for future wearable/implantable LED phototherapy devices.
Selecting the appropriate soft substrate based on the intended application is a key step toward achieving device flexibility and stretchability (Fig. 5a). Textile-based substrates, with their breathability and softness, are particularly suitable for large-area treatment scenarios, such as phototherapy garments for jaundice treatment, phototherapy knee braces for arthritis management, and phototherapy caps for promoting hair growth. Hydrogel substrates, known for their high biocompatibility and transparency, are preferred for devices in direct contact with the skin or organs. Polymer substrates, which balance mechanical strength and flexibility, are better suited for highly deformable regions and implantable phototherapy devices. Current soft substrates face significant challenges in conforming to complex biological surfaces (e.g., brain gyri or joint folds). As shown in Fig. 4a (left), the elastic modulus of brain and lung tissues is an order of magnitude lower than that of common polymer substrates (PI, PET, PDMS, SEBS), and the grooves in regions like the brain and skin hinder full adhesion of flexible phototherapy devices, affecting treatment uniformity. Flexibility is influenced by device thickness, Young's modulus, and width, with studies showing that a thickness of 10-100 μm ensures effective brain tissue adaptation. Ultra-flexible nanoelectronics (<10 μm feature size, 1 μm thickness) can further reduce chronic inflammation. Currently, phototherapy devices are often fabricated on polymer substrates, and researchers have employed various methods to optimize the interface compatibility with tissues. OLED and QLED devices have achieved thicknesses around 10 μm, offering excellent flexibility, while micro-LEDs can enhance tissue and organ compatibility and phototherapy efficacy through substrate design (octopus' structure).
To address the temperature tolerance of new materials, low-temperature fabrication techniques are better suited for future LED phototherapy devices (Fig. 5b). Methods like inkjet and 3D printing enable precise fabrication of complex structures while optimizing conductive ink properties for multilayer flexible circuits. Spin-coating further improves the uniformity and optical performance of emissive layers with precise film thickness control (Fig. 5b).
The manufacturing processes for soft emission components are continuously optimized to improve efficiency and reduce costs (Fig. 5c). Laser-induced transfer technology enables high-precision and large-scale production of µLEDs, making them one of the most promising solutions for future phototherapy applications. Meanwhile, thermal evaporation techniques and advanced spin-coating methods significantly enhance the luminous efficiency and lifespan of OLED and QLED devices by improving the fabrication of the emissive layer. When combined with elastomers, OLED and QLED devices exhibit enhanced stretchability and flexibility. Both of these light-emitting components can achieve ultra-uniform surface emission and meet the optical power requirements of phototherapy. Additionally, Surface-Mount Device LEDs can be directly integrated into phototherapy devices through soldering (Fig. 5c).
To preserve the softness and thinness of future LED phototherapy devices, atomic layer deposition (ALD) (Fig. 5d) can sequentially deposit organic and inorganic layers, providing effective water and oxygen barriers. ALD's self-limiting growth mechanism ensures smooth atomic surfaces and uniform nanoscale films, making it a promising approach for thin-film encapsulation.
The power supply for future LED phototherapy devices should be tailored to specific application requirements (Fig. 5e). For wearable devices, rechargeable micro-batteries are ideal, offering extended use for applications such as acne, wounds, and psoriasis. Implantable devices for short-term applications may utilize high-energy-density micro-batteries or soft batteries, particularly for treating heart diseases, cancer, and deep tissue disorders. Long-term implantable devices require wireless power transfer systems to provide sustained energy supply. While wireless coils are commonly used, their size constraints limit achievable power levels and application scenarios. Alternative methods, including RF communication, ultrasound, infrared, and energy harvesting technologies like piezoelectric nanogenerators or self-powered systems, show potential but are insufficient for high-power phototherapy applications. However, their real-time power output often falls short of the demands of high-intensity phototherapy applications, necessitating battery storage to ensure a reliable and continuous energy supply.
The integration of sensors is pivotal for enhancing the intelligence of phototherapy devices (Fig. 5f). Electrodes for electrochemical and electrophysiological sensors are typically patterned using laser engraving, with functional materials deposited to enable targeted data collection. Photoelectric detectors, based on spectroscopic principles, are fabricated similarly to LED emissive materials, while pre-packaged detectors can be soldered directly onto flexible circuits. As shown in Fig. 5g, the design of future phototherapy devices incorporates micro-processing chips that collect sensor data and use built-in algorithms to dynamically adjust treatment parameters in real time. Sensors monitoring parameters such as tissue oxygen levels, skin temperature, and light absorption enable real-time feedback and optimization of therapy, ensuring maximum efficacy tailored to specific clinical conditions.
Integrating sensors that monitor physiological parameters marks a significant advancement in phototherapy device technology. These sensors enable real-time feedback and dynamic optimization of treatment parameters, ensuring maximum therapeutic efficacy by adapting to specific clinical conditions. Seamless integration of sensors during device fabrication enhances functionality, streamlines design, and creates compact, efficient systems that reduce manual adjustments and improve adaptability across diverse clinical scenarios. Future devices, leveraging advanced Internet of Things technologies, will better meet clinical needs and address the growing demand for professional phototherapy services in home settings, further broadening the scope and impact of phototherapy technology.