Microscale LEDs in Biomedical Imaging and Therapy

By Owais AliApr 16 2024Reviewed by Lexie Corner

The relentless pursuit of miniaturization in electronics has revolutionized various fields, including biomedical sciences. Advancements in light-emitting diode (LED) technology, particularly in the development of microscale LEDs, have opened up new frontiers in biomedical imaging and therapy. 

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These small yet highly efficient light sources offer a unique combination of small footprint, long lifespan, high brightness, and low power consumption, making them ideal for integration into implantable and wearable biomedical devices.

Basics of Microscale LEDs

Microscale light-emitting diodes (micro-LEDs) are miniature versions of traditional LEDs, typically ranging from 1 to 100 micrometers in size. Their microscopic scale allows for unprecedented control and precision, seamless integration into flexible substrates for minimal tissue damage and unrestricted movement during in vivo studies.¹

A microscale LED comprises an active region between n-type and p-type semiconductor layers. When an electrical current is applied, electrons from the n-type layer and holes from the p-type layer recombine in the active region, releasing energy as photons or light. The wavelength of the emitted light depends on the semiconductor materials used and the composition of the active region.²

Various materials, such as GaN, InGaN, GaP, GaAs, and InP, offer a wide range of emission wavelengths from ultraviolet to infrared, providing versatility for addressing diverse biomedical requirements.

Selecting the appropriate material is crucial to achieve the desired wavelength. For instance, microscale LEDs emitting light within the "biological transparency window wavelength" (650-950 nm) can penetrate deeper into tissues, facilitating applications like in-situ photometry and wireless implantable light sources for optogenetic stimulation and therapy.

Advanced fabrication techniques, including controlled spalling, laser, and chemical lift-off, facilitate the production of substrate-free thin-film devices with steady operational performance and desired mechanical properties. These approaches reduce device weight and thickness and enable the development of deformable bio-integrated optoelectronic devices.^3,4

Microscale LEDs in Biomedical Imaging

Microscale LEDs have emerged as powerful tools in various biomedical imaging techniques, offering advantages over conventional light sources in miniaturization, deep tissue penetration, and wireless operation.

Continuous Imaging of Local Hemoglobin Dynamics

Monitoring tissue oxygenation levels is crucial for understanding physiological and pathological processes. However, current methods face limitations in in-depth penetration and require physical tethers and anesthetics, which affect natural behaviors. This highlights the need for reliable monitoring systems for improved insights into biological processes and clinical diagnostics.

A study published in Science Advances developed an implantable oximetry probe using red (625 nm) and green (540 nm) microscale LEDs and a photodetector to continuously monitor regional tissue oxygen saturation (rStO2).

Its lightweight, mechanically compliant design minimized physical and immune responses upon implantation, while RF-based wireless and IR-based data transmission ensured uninterrupted monitoring without affecting the natural behavior of animals, representing a significant advancement over conventional technologies like near-infrared spectroscopy (NIRS) or cerebral oximeters.⁵

Wireless Imaging Neuronal Dynamics in the Deep Brain

Studying neuronal dynamics with anatomical, cellular, and time-locked specificity in mammals is important for understanding the connections between neuronal processes and behaviors.

Implantable fiber-optic cables offer sophisticated neural recording capabilities; however, their physical constraints hinder natural behaviors and complicate studies in complex environments.

A study published in Proceedings of the National Academy of Sciences developed a wireless, implantable fluorescence photometer featuring a microscale LED light source on flexible polymer support for minimally invasive implantation into deep brain regions.

The device detected transient calcium ion changes signaling neuronal activity, overcoming limitations of traditional fiber-optic systems by enabling wireless operation and direct brain insertion without tethering animals.⁶

Microscale LEDs in Therapy

Beyond imaging, microscale LEDs have demonstrated remarkable potential in therapeutic interventions, offering precision and control in targeting and treating diseased cells or tissues.

Micro-Scale Led Guided PDT to Boost Antitumor Immunity

One groundbreaking application uses an implantable micro-LED device in photodynamic therapy (PDT) for cancer treatment. This innovative approach activates photosensitizers with mild visible light directly within the tumor, inducing immunogenic cell death without harming surrounding healthy tissues.

By avoiding the immunosuppressive effects of necrotic cell death caused by intense light penetration into deep tissues, this micro-LED guided PDT technique enhances antitumor immunity, offering the potential for more effective cancer treatments.⁷

Recurrent Photon Treatment for Diabetic Retinopathy

Diabetes mellitus leads to complications like retinopathy, nephropathy, and neuropathy. Current treatments, including laser therapy and eye injections, are invasive and often result in poor patient compliance, highlighting the need for less invasive alternatives.

Microscale LEDs offer unprecedented precision and control in targeting and treating diseased tissues, minimizing collateral damage and enhancing therapeutic outcomes.

In a study published in Advanced Science, researchers designed a wireless, non-invasive luminescent contact lens incorporating a micro LED emitting near-infrared/far-red light.

The designed lens, featuring LEDs, wireless power, communication systems, and circuit chips on a single PET film cross-linked with silicone elastomer, maintained a temperature below 40 °C during operation, preventing additional thermal damage.

In vitro studies showed a reduction in retinal vascular hyper-permeability over eight weeks with 120 µW light irradiation for 15 minutes thrice a week, confirming the feasibility and safety of microscale LED contact lenses for treating retinopathy.⁸

Challenges and Solutions

While microscale LEDs offer numerous advantages, their integration into biomedical devices and applications presents several challenges.

A significant hurdle is the power requirement for these implantable optoelectronic devices. While traditional external batteries provide sufficient and stable power, they pose limitations in size, weight, and the need for replacement.

Ongoing research efforts are focused on addressing these challenges through innovative solutions. For instance, developing flexible piezoelectric devices capable of generating electrical pulses from mechanical energy offers a promising self-powered solution for deep brain stimulation.

The integration of wireless data transfer technologies, such as Bluetooth and near-field communication (NFC), will also enable remote signal transfer and wireless system operation, further enhancing the versatility and functionality of these devices.³

Another challenge is ensuring the biocompatibility and longevity of these implantable devices. Advanced encapsulation techniques and selecting appropriate biocompatible materials are crucial to mitigate immune responses and ensure long-term functionality within the biological environment.

Researchers are exploring various biocompatible polymers, ceramics, and coatings to create robust and stable encapsulations that can withstand the harsh conditions of the body while preventing leaching of materials or degradation over time.⁹

Future Perspectives and Conclusion

The field of microscale LED technology in biomedical sciences is rapidly evolving, with ongoing research and potential breakthroughs on the horizon. As fabrication techniques continue to improve and new materials are explored, we can expect even smaller, more efficient, and more versatile microscale LED devices capable of addressing a broader range of biomedical applications.

Emerging applications may include targeted drug delivery systems, optogenetic stimulation for neurological disorders, and real-time monitoring of physiological parameters in various organs and tissues.

Integrating microscale LEDs with other emerging technologies, such as nanotechnology and artificial intelligence, could lead to unprecedented advancements in personalized medicine and precision healthcare.

As research in this field progresses, microscale LEDs are poised to play a crucial role in advancing diagnostic, imaging, and therapeutic modalities in medicine, ultimately improving patient outcomes and quality of life.

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References and Further Reading

1. Photonics Marketplace. (2024). Micro-LED. [Online] Photonics Marketplace. Available at: https://www.photonics.com/EDU/micro-LED/d8186
2. Adhikary, A., et al. (2022). Light intensity and efficiency enhancement of n-ZnO/NiO/p-GaN heterojunction-based white light-emitting diodes using micro-pillar array. Journal of Optics. doi.org/10.1007/s12596-022-00836-w
3. Zhang, H., Peng, Y., Zhang, N., Yang, J., Wang, Y., Ding, H. (2022). Emerging optoelectronic devices based on microscale LEDs and their use as implantable biomedical applications. Micromachines. doi.org/10.3390/mi13071069
4. Chen, J., Ding, H., Sheng, X. (2024). Advanced manufacturing of microscale light-emitting diodes and their use in displays and biomedicine. Journal of Information Display. doi.org/10.1080/15980316.2023.2248403
5. Zhang, H., et al. (2019). Wireless, battery-free optoelectronic systems as subdermal implants for local tissue oximetry. Science advances. doi.org/10.1126/sciadv.aaw0873
6. Lu, L., et al. (2018). Wireless optoelectronic photometers for monitoring neuronal dynamics in the deep brain. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.1718721115
7. Choi, J. (2022). Implantable micro-scale LED device guided photodynamic therapy to potentiate antitumor immunity with mild visible light. Biomaterials Research. doi.org/10.1186/s40824-022-00305-2
8. Lee, G. H., et al. (2022). Smart wireless near‐infrared light-emitting contact lens for the treatment of diabetic retinopathy. Advanced Science. doi.org/10.1002/advs.202103254
9. Smith, J., Lamprou, D., Larson, C., Upson, S. (2021). Biomedical applications of polymer and ceramic coatings: a review of recent developments. Transactions of the IMF. doi.org/10.1080/00202967.2021.2004744.

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