Introduction
Biomedical nanotechnology is one of the most exciting fields with some extraordinary innovations in recent years that could revolutionize how we diagnose and treat medical conditions. Nanoscience promises targeted drug delivery and imaging techniques that are less invasive and toxic, with many of these applications already in clinical trials. It also promises to revolutionize miniaturized medical devices, coatings, and surface treatments as this technology continues to evolve. This field will only get more advanced, and the analysis industry will have to keep up with these trends. Current approaches to imaging and analysis such as assays and mass spectrometers struggle to quantify nanoparticle properties such as size and morphology, and x-ray techniques require advanced sample preparation. Previously, more high-precision imaging techniques such as electron and atomic force microscopy resulted in damage to sensitive samples and were often unnecessary. However, the field of biomedical imaging has advanced significantly in the last two decades, culminating in a powerful suite of analysis solutions that can image samples that were previously thought to be impossible. This article details some of the most exciting advancements in biomedical imaging that can help enhance product development and secure regulatory compliance.
History and Timeline of Advances
The field of biomedical imaging has evolved rapidly over the past century. Traditional optical microscopy has been used since the 17th century, but the resolution limit of light (~200 nm) constrained its applications in nanobiology. The invention of the electron microscope in the 1930s enabled imaging at much higher resolution, allowing researchers to visualize structures at the nanoscale. The development of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) in the mid-20th century revolutionized material science and biology.[1] The 1980s saw the advent of atomic force microscopy (AFM), allowing for nanoscale topographical imaging.[2] More recently, innovations such as cryogenic electron microscopy (CryoEM) and environmental SEM have further enhanced the ability to study biological structures without causing damage. Atomic-scale imaging of proteins with CryoEM marked a significant milestone in bioimaging, winning in the Nobel Prize in chemistry in 2017.[3]
Electron Microscopy Innovations
Electron microscopy relies on a vacuum chamber and a high-energy electron beam, both of which can damage samples and even result in tool damage due to evaporation and sublimation of liquids in the sample. Drying out a biological sample can alter its morphology, making it unsuitable for understanding structures in their native states. However, recent advances in biomedical electron microscopy have made it possible to acquire high-quality nanoscale images of structures such as nanoparticles, proteins, and viruses, enabling innovation in nanomedicine.
Cryogenic electron microscopy preserves delicate biological structures by flash-freezing samples within milliseconds, preventing damage from radiation exposure. Low-energy electron beams are then used to image these samples with minimal disruption. CryoEM has been used to capture detailed images of protein folding, RNA structures, and lipid-based nanoparticles such as liposomes, making it a critical tool for structural biology and drug development.[4]
Additionally, advancements in transmission electron microscopy are enabling atomic-scale imaging of thin slices (lamella) of tissue and biological systems. Cryogenic and low voltage TEM offers gentler sample preparation and imaging conditions, facilitating angstrom-scale biological imaging. Samples can even be prepared using cryogenic focused ion beam milling in order to minimize damage.[5] And cryogenic and low vacuum energy-dispersive X-ray spectroscopy (EDS) is making strides in mapping the elemental composition of nanoscale biological structures. These innovations could eventually replace less precise techniques such as mass spectrometry in certain applications.[6]
Furthermore, environmental and low-vacuum SEM are powerful imaging techniques for sensitive biological samples. In these methods, the SEM chamber is not fully evacuated, reducing the risk of sample damage. Although image resolution is slightly lower due to electron scattering in the gas medium, these techniques offer a viable solution for imaging hydrated or delicate samples.[7]
Atomic Force Microscopy
Atomic force microscopy (AFM) is one of the most powerful techniques for surface characterization. An AFM uses a nanoscale surface probe that scans over the sample, with the deflection measured by a laser. In a vacuum environment, AFM is sensitive enough to characterize individual atoms on a surface. Advances in AFM have allowed for the direct measurement of biological structures such as live cells, DNA, and proteins.[8]
One significant advancement is liquid AFM, where the cantilever is immersed in a liquid medium. This technique enables imaging of biological structures in physiologically relevant conditions, preserving their morphology and function. AFM is increasingly used in biomedical applications as an alternative (or enhancement) to traditional techniques like assays and mass spectrometers that are expensive and time-consuming. Additionally, AFM can probe mechanical properties such as hardness and elasticity, making it a valuable tool as medical devices and therapies miniaturize and incorporate nanotechnology.[9]
Miniaturization of Medical Devices and Outlook
The miniaturization of medical devices is driving the need for more advanced imaging techniques. As devices such as stents, catheters, and endoscopes shrink in size, traditional imaging methods struggle to provide the necessary resolution for quality control and development. High-resolution electron microscopy and AFM are becoming essential for ensuring the integrity and functionality of these miniature medical components. Nanoparticle-based drug delivery systems and implantable biosensors also require precise characterization to meet regulatory standards. The trend toward smaller, more efficient medical devices will continue to push the boundaries of imaging technology.[10],[11],[12]
Future Outlook
The future of biomedical imaging is poised for further breakthroughs. Emerging technologies such as super-resolution microscopy, quantum imaging, and AI-enhanced image processing are expected to revolutionize the field. Super-resolution techniques such as phase contrast microscopy allow for optical imaging below the diffraction limit of light, providing unprecedented detail at the nanoscale.[13] Quantum imaging methods, leveraging entangled photons, promise even greater sensitivity and resolution for biological imaging.[14] Finally, AI and machine learning are being integrated into imaging workflows, improving image reconstruction, noise reduction, and pattern recognition.[15] These advancements will enable faster, more accurate diagnostics and pave the way for real-time imaging in medical applications.
Market Outlook
The global biomedical imaging market is projected to grow significantly, driven by increased demand for high-resolution imaging in medical diagnostics, drug development, and nanotechnology applications. The electron microscopy market alone is expected to double over the next decade, fueled by advancements in CryoEM, SEM, and TEM.[16] The rising prevalence of chronic diseases and the need for personalized medicine will further drive demand for cutting-edge imaging techniques. Additionally, regulatory agencies are placing greater emphasis on nanotechnology-based medical devices, necessitating advanced imaging solutions for compliance and quality control.[17]
As imaging technology continues to evolve, its applications in nanobiology will expand, offering new possibilities for research, diagnostics, and therapeutics. Companies that invest in these emerging technologies will be well-positioned to lead in this rapidly growing field. If you think advanced analysis could benefit your business, feel free to reach out to us at info@nanolab.llc for a free consultation!
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