Fig. 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.

Fig. 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.

Fig. 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.

Fig. 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 μ-ILED and a μ-IPD at the tip end. (b) Left: optical micrograph of the injectable photometry probe. The tip has a total width of ∼350μm and a thickness of ∼150μm. The weight is 29 mg; (b) Right: magnified colorized SEM image of the tip (orange, PI; yellow, interconnection; blue, μ-ILED; green, μ-IPD with an optical filter). [Scale bars, 2 mm (left) and 200μm (right).] (c) Upper: schematic illustration of a GaAs μ-IPD; Lower: SEM image of a representative μ-IPD (lateral dimensions of 100μm×100μm and a thickness of 5μm). Metal electrodes are colored yellow. (Scale bar, 50μm.) (d) Schematic exploded-view illustration of a transponder. (e) Photographic image of the wireless detachable transponder on the fingertip. (Scale bar, 1 cm.) (f) Images of the separated transponder and injectable (left) and the integrated system in operation (right). The transponder is connected only during signal recording. [scale bars, 4 mm (left) and 8 mm (right).] (g) Image of a freely moving mouse with a photometry system (1 week after surgery). (scale bar, 7 mm.) (h) Schematic illustration of the electrical operating principles of the system: read out and control occur with a detachable wireless transponder that also facilitates signal amplification and digitalization. The signal is transmitted via an IR-LED with a modulation frequency of 38 kHz for single-transponder operation and an additional 56 kHz in dual-transponder operation. A receiver system demodulates the signal and sends the received data to a personal computer (PC) for data storage. Figures reproduced from Ref. 35, under CC-BY license.

Fig. 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.

Fig. 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.

Fig. 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.

Fig. 8. μ-LED-based oCI. (a) Optically evoked auditory brainstem response in an AAV-CatCh-injected gerbil in response to a 1 ms laser pulse of ∼35mW (mean of 1000 stimulus presentations at 10 Hz repetition rate); Catch-eYFP-expressing SGNs in the apical cochlear turn identified by parvalbumin expression (b) and CatCh-eYFP (c). The inlay (D’) of the merged immunostaining (d) indicates the lack of CatCh-EYFP signal in inner hair cells (dashed white line). Scale bar: 20μm; Scanning electron micrographs of a μ-LED (60μm×60μm footprint) structured on a sapphire substrate showing the nonemitting p-contact side (e) and the emitting side of a μ-LED (f), transferred onto and embedded into an epoxy substrate. The GaN surface of the μ-LED has been roughened by KOH etching, showing characteristic pyramidal structures; (g) Picture of an oCI carrying 16 individually addressable μ-LEDs with a pitch of 100μm on a flexible substrate, μ-LEDs #5 and #13 (from the tip) are active; (h) Radiant flux of individual μ-LEDs as a function of driving current. The thick line indicates the mean, whereas the error bars indicate the SD of the mean. Nonfunctional μ-LEDs (which did not emit light, 158 out of 560 μ-LEDs) have been excluded; (i) oCI inserted into the cochlea (dashed black lines) via a cochleostomy in the basal cochlear turn (black, solid line). The round window niche is highlighted by a dashed white line, the round window by a solid white line. SA: stapedial artery; (j) 3D X-ray tomography reconstruction of a 16-channel oCI implanted in a gerbil cochlea via the round window. Cables and μ-LEDs are marked in blue, and the most apical μ-LED is indicated by the black arrowhead; the basilar membrane is marked in green. μ-LEDs have a size of 60μm×60μm. Figures reproduced with permission from Ref. 21, under CC-BY license.

Fig. 9. (a) Conceptual illustration of trichogenic photostimulation via monolithic red f-VLEDs (top). Photographs of mouse dorsal skin in control, f-VLED-treated, and MNX-treated groups (bottom) after 20 days of hair-regrowth experiments. (b) Hair-regrowth area as a function of skin stimulation days (top). Hair-regrowth experimental results of f-VLED-treated and MNX-treated mice, which were treated for 20 consecutive days. (bottom) Number of mice used for analyses: light-treated, n=4; MNX-treated, n=4; negative control, n=4. (c) Extracted hair images of mice after biological experiments (top) after 20 days. Comparison of hair-growth length after trichogenic treatments (bottom) (*p<0.05, paired t test). Histological and immunofluorescence results of stimulated mouse dorsal skin in (d) control (upper), MNX (middle), and f-VLED (bottom) groups {(i) H&E stained images, (ii) β-catenin stained images, (iii) DAPI stained images, (iv) merged images}. Figures reproduced from Ref. 20 with permission, © 2018 American Chemical Society (ACS).

Fig. 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.