Spinal cord injury (SCI) affects approximately 2.5 million people worldwide. The primary phase of SCI is initiated by mechanical trauma to the spinal cord, while the secondary phase involves the ensuing tissue swelling and ischemia that worsen tissue damage and functional outcome. Optimizing blood flow to the spinal cord after SCI can mitigate injury progression and improve outcome. Accurate, sensitive, real-time monitoring is critical to assessing the spinal cord perfusion status and optimizing management, particularly in those with injuries severe enough to require surgery. However, the complex anatomy of the spinal cord vasculature and surrounding structures present significant challenges to such a monitoring strategy. In this study, Doppler ultrasound was hypothesized to be a potential solution to detect and monitor spinal cord tissue perfusion in SCI patients who required spinal decompression and/or stabilization surgeries. This approach could provide real-time visual blood flow information and pulsatility of the spinal cord as biomarkers of tissue perfusion. Importantly, Doppler ultrasound could be readily integrated into the surgical workflow, because the spinal cord was exposed during surgery, thereby allowing easy access for Doppler deployment, while keeping the dura intact. Doppler ultrasound successfully measured blood flow in single and bifurcated microfluidic channels at physiologically relevant flow rates and dimensions in both in-vitro and in-vivo porcine SCI models. Furthermore, perfusion was quantified from the obtained images. Our results provide a promising and viable solution to intraoperatively assess and monitor blood flow at the SCI site to optimize tissue perfusion and improve functional recovery in SCI patients.
Efficient methods for the accurate analysis of drug toxicities are in urgent demand as failures of newly discovered drug candidates due to toxic side effects have resulted in about 30% of clinical attrition. The high failure rate is partly due to current inadequate models to study drug side effects, i.e., common animal models may fail due to its misrepresentation of human physiology. Therefore, much effort has been allocated in the development of organ-on-a-chip models which offer a variety of human organ models mimicking a multitude of human physiological conditions. However, it is extremely challenging to analyze the transient and long-term response of the organ models to drug treatments during drug toxicity tests, as the proteins secreted from the organ-on-a-chip model are minute due to its volumetric size, and current methods for detecting said biomolecules are not suitable for real-time monitoring. As protein biomolecules are being continuously secreted from the human organ model, fluorescence techniques are practically impossible to achieve real-time fluorescence labeling in the dynamically changing environment, thus making a label-free approach highly desirable for the organ-on-achip applications. In this paper, we report the use of a photonic-crystal biosensor integrated with a microfluidic system for sensitive label-free bioassays of secreted protein biomolecules from a heart-on-the-chip model created with cardiomyocytes derived from human induced pluripotent stem cells.
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