With advancement of micromanufacturing processes in conjunction with innovative material discoveries have expanded application of light emitting diodes (LEDs) into bio-medical fields. Distinct characteristics of micro-LEDs such as dimensions in micrometer scale, outstanding power efficiency, high stability and self-emitting characteristics to list a few, have promoted micro-LEDs as a principal light source in increasing phototherapy devices. Furthermore, owing to the benefits of miniscule dimensions of micro-LEDs, researchers have developed innovative flexible form-factor LEDs for diverse applications such as portable or conformal patch type phototherapy devices, which are inaccessible with previous optoelectronic devices made from laser light source.

While diminutive dimensions of micro-LEDs enable such unprecedented devices, integration of the light source into device format exhibits vast challenge of micro-LED manipulation since conventional pick and place methods using traditional gripper tools are impractical due to higher surface adhesion effect over volumetric energy. Hence, reversible and controllable adhesive manipulator tools for microscale arrangement have been developed for wide range of heterogeneous micro-LED material integration for biomedical applications.

An unique characteristic of micro-LED manufacturing is that while processes involve immensely expensive practices, owing to the batch production of individual functional units yields compellingly low price per individual units. Therefore, in order to maximize the cost efficiency, manufacturers systematically design the micro-LEDs in extremely dense arrangement regardless of final device design. Albeit of practical cost-effective spatial arrangement, micro-LEDs demand further manipulation for where individual devices are detached from the processed substrate and implanted onto electrical interconnects for functional utilization. Owing to the unusual characteristics of surface effects over volumetric effects in microscale objects as shown in Fig. 1A, such integration process requires extraordinary manufacturing technique termed ‘transfer printing’ as shown in Fig. 1B. The process protocols initiate with microscopic alignment of a manipulator designed in specific arrangement followed with exfoliation of the micro-LED array in the preassigned regions. The manipulator with micro-LEDs attached is transferred onto separate target substrate often with defined metallic electrical interconnect lines and subsequently printing the array of micro-LEDs onto destined location with extreme precision.

Figure 1. (A) Body, surface, and line effects versus dimensions in log scale. (B) Overall schematic description of transfer printing process. LED, light emitting diode.

Competing fracture mechanics at micro-LED and manipulator versus micro-LED and substrate is the principal operation mechanism of transfer printing as shown in Fig. 2. It is the competing adhesion force between micro-LED-manipulator versus micro-LED-substrate where if the former interface displays higher adhesion, the array of micro-LEDs are exfoliated and adhered onto the manipulator for subsequent printing process during which the adhesion force between micro-LED-substrate interface is higher than the other. To achieve tunable adhesion at interfaces, researchers have developed two main approaches, laser lift off (LLO) and mechanical exfoliation techniques. LLO technique is vastly adopted in micro-LED based display manufacturing industries with its high precision and short tact time, but the process suffers from laser transparent substrate material as well as relatively expensive capital investment for laser source. On the other hand, mechanical exfoliation techniques ranging from sacrificial layer removal process with tethering design is comparatively rapid integration and low-cost process but integrating tethering design reduces estate for micro-LED formation as well as sacrificial layer removal process for preparation for transfer printing impedes overall tact time. Various approaches of transfer printing such as dry transfer printing using thermal mismatch at interface,¹ interfacial chemistry manipulation,^2,3 graphene interlayer to control interfacial adhesion,^4,5 utilization of polymer interlayer^6,7 have all been demonstrated their capabilities in reducing interfacial adhesion for transfer printing, yet to be further verified for micro-LED transfer printing owing to extreme environments for manufacturing micro-LEDs.

Figure 2. Competing fracture mechanics at the interfaces between micro-LED-manipulator and micro-LED-substrate to describe exfoliation and printing processes. LED, light emitting diode.

Successful transfer printing is not only mandated to surface adhesion between device and the micro-LED but also resides in the reversible or controllable adhesive manipulator. Frequently used elastomer manipulator is based on polydimethylsiloxane (PDMS), which exhibits viscoelastic characteristics for adhesion control through separation velocity.⁸ Upon contacting with an opposing material, high velocity separation upsurges the adhesion for convenient “pick-up” process, while lower peeling velocity decreases adhesion for printing process. Major advantage of PDMS manipulator resides in its chemically inert and dehydrated process protocols which surrenders residues on the interface for immaculate surface for electrical and micro-mechanical device establishments. Followed with PDMS application as a micro-manipulator in 2006, numerous explorations to increase rather low adhesion on/off ration of PDMS flat surface have been conducted largely in mechanical, magnetic, electrostatic force incorporated manipulators.

Inspired by gecko’s ability to climb, researchers have explored different measures to increase the adhesion on/off ratio. Microscale pyramid structured PDMS manipulators operate by adopting restoration energy of the material.^9-12 The pyramid structures are compressed upon preload against an opposing surface result in large contact area between the PDMS manipulator and the surface, hence large adhesion force. On the other hand, upon picking up a device (i.e., micro-LED), the preload is released and the pyramid is restored to its original configuration to display minimal contact area at the tip of the pyramid structures. Exploiting such restoration energy of micro-pyramid structure, the advanced form manipulator displays over 3 order of adhesion on/off ratio for facile transfer printing. Pedestal is another form of mechanically controlled PDMS reversible adhesive manipulator which is structured to have smaller post with relatively large contact pad.¹³ Conventionally, delamination initiates at the edge of two contacting surfaces and propagates along the interface, but pedestal structured manipulator with relatively small post lateral dimension compared with large contact pad shows altered results where delamination starts internal region of the contact pad near post, hence resulting in 15 folds higher adhesion force than flat slab of manipulator. Shear induced controllable transfer printing technique had developed to reduce adhesion for convenient printing process to increase adhesion on/off ratio.^14-16 Likewise, instead of normal post, angled directional post had developed to induce interfacial edge crack upon directional shear stress, which showed approximately 30 times of adhesion force compared with lower adhesion state.¹⁷

In addition to endeavor to increase adhesion on/off ratio by employing manipulator structure, additional mode of external stimuli such as magnetic^18,19 or electrostatic²⁰ forces to accomplish successful transfer printing results have researched. Magnetic-responsive thin films are embedded in the manipulator which deflects upon exposure to magnetic field and subsequent concave structure induce edge crack propagation for convenient printing process. Likewise, Luxvue and Apple, two major leading corporations are developing electrostatic transfer heads with mesa structure consisting of the substrate-supported electrode layer and dielectric layer.²¹ When a voltage is applied to the array of electrostatic transfer heads, an electrostatic attraction force that attracts each other is generated for convenient pick-up and printing processes. Magnetic and electrostatically driven micro-transfer manipulators are advanced form of conventional PDMS structured manipulators with higher adhesion on/off ratio and superior control of adhesion, but additional external stimuli can cause impairments on transferred objects such as micro-LED, which requires further modification and improvement for broader adaptations. Thermally actuated transfer printing have also been proposed by Luo et al.²² in 2021, where hermetically sealed interface between manipulator and device with pressure inside the cavity of manipulator is tuned by temperature. Albeit of advances in transfer printing manipulator tools, more credible and reliable apparatus with expediting operating mechanism in cost-effective manner needs to be developed for wider adaptation of micro-LED in integrated photo-biomodulation or phototherapy purpose.

The micro-LEDs transferred from grown substrate onto functional devices require means to electrically and mechanical interconnected with pre or post defined electrical lines intact for practical use since transferred micro-LEDs are merely bond to the devices via weak surface interactions such as Van der Waal’s force (Fig. 3A). Traditionally, anisotropic conductive pastes (ACP), which presents thermosetting resin containing conductive particles, is dispensed between chip and the electrical lines followed with thermal compression to unfold the thermosetting resin, which mechanically bonds the chip while conductive particles establish electrical lines (Fig. 3B).^23-26 While ACP bonding technique is most widely used in industry, as micro-LEDs are becoming more miniscule, the contact pad dimensions on the micro-LEDs are becoming smaller accordingly. ACP is generally 5 μm in diameter and allocating a single ACP bead on the micro-LED contact pad is absurdly demanding for industrial adaptation. Hence, adhesiveless direct bonding methods are investigated such as cold welding^27-30 and eutectic bonding^31-34 inspired by microelectromechanical system (MEMS) packaging techniques. Cold welding is different from conventional liquids molten phases welding in a way that cold welding is a solid-state welding process utilizing atomic diffusion in nanoscale (Fig. 3C). Diffusion barrier in a single metal atom is low enough to overcome at room temperature or with small external pressure, and its bonding results are on par with solid metal. However, the process requires further modifications on electrical pads to achieve intimate contact in atomic scale, which is not yet prevailing. Another more practical method of electrically and mechanically bond onto the substrate is by using eutectic point in binary or tertiary metal interfaces (Fig. 3D).^35-37 Unlike direct bonding requiring relatively high melting temperature, at specific composition according to the phase diagram, the eutectic bonding is achieved at relatively low temperature, low pressure and short bonding time. For example, gold (Au) and tin (Sn) bonds at 280°C, Au and indium (In) bonds at 156°C, which is compatible with other micromanufacturing processes. Such relatively low temperature become exceedingly compelling route for microscale object integration and further can be adopted for micro-LED based phototherapy devices.

Figure 3. (A) Overall view of micro-LED and PCB board integration schematic. (B) Anisotropic conductive paste bonding at metal bonding interface. (C) Homogeneous metal-metal cold welding. (D) Eutectic bonding with eutectic alloy formation for low temperature bonding. LED, light emitting diode; PCB, printed circuit board; ACP, anisotropic conductive pastes.

Micro-LEDs operate identically with conventional LEDs, which is a light source with specific wavelength with exception of miniscule dimension for higher efficiency, low operating temperature and flexibility in device form factor. Micro-LEDs can be integrated as a stand-alone functional device to induce photochemical reactions in biological systems for photobiomodulation (PBM) or phototherapy (PBT, PBMT) application. Specifically, these phototherapy devices are utilized to treat pain relief,^38-40 sports injuries,^41,42 reduce inflammation,⁴³ skin regeneration.^44-46 Furthermore, micro-LED based phototherapy devices exhibit potential as a tool for treating neurological diseases based on the recent results from pioneering works. Different research groups are investigating the effect of PBM on brain to treat Parkinson’s and Alzheimer’s diseases, which have shown significant improvements based on mouse experiments.^47-49 These effects are speculated by stimulating c-kit-positive mesenchymal stem cells (MSCs) in autologous bone marrow (BM) to enhance the capacity of MSCs to infiltrate the brain and clear β-amyloid plaques.⁵⁰

Micro-LEDs integrated with other sensing components are capable of operating as optoelectronic or optomechanical sensor to monitor biophysical signals such as photoplethysmogram (PPG),⁵¹ fingerprint sensor,⁵² glucose,^53,54 NO₂⁵⁵ and pH.⁵⁶ Aforementioned micro-LED based biosensor devices are yet to be extensively adopted and commercialized, but with its unique characteristics of miniscule form-factor, micro-LED integrated sensors and stimulators are promising as a next-generation wearable and implantable biosensors.

Micro-LED based phototherapy or PBM devices are exhibit unprecedented potential with its exceptional stability, lifetime, energy efficiency and its miniscule form factor for pervasive device applications. Recent advances in micromanufacturing and heterogeneous material integration technique have further widened micro-LED applications in phototherapy by developing flexible form factors. Transfer printing process, which delivers and locates microscale objects to geographically predetermined location with microscopic precision requires further improvement in cost-effective manner. Distinct elastomer manipulators along with expedited electrical and mechanical bonding techniques have been explored in attempts to improve transfer printing efficiency but no single method is dominantly superior to other for industrial adaptation. With further progress in micro-LED integration and device manufacturing techniques, extraordinary devices such as wearable and reusable phototherapy devices, implantable PBM devices can be universally employed for preferrable medical and healthcare applications.

This study was carried out with the support of ‘R&D Program for Forest Science Technology (Project No. “2021396B10-2223-0107”)’ provided by Korea Forest Service (Korea Forestry Promotion Institute).

No potential conflict of interest relevant to this article was reported.