Ultrasensitive Photonic Microsystem Enabling Sub-micrometric Monitoring of Arterial Oscillations for Advanced Cardiovascular Studies

Figures

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  Figure 1. Numerical evaluation of opto-mechanical performance of the lightguide-cantilever. (A) Image of the mechanical response of the 3D model of the microsystem after exposure of the blood vessel to 120 mmHg intraluminal pressure. (B) Representation of a variation in deflection angle and displacement with the applied intraluminal pressure according to ANSYS numerical analysis, when considering the model presented in (A). (C) Performance of the optomechanical sensing of the microsystem with the tip of the lightguide-cantilever displacing to the right (black arrow) in response to mechanical forces. Figure also includes irradiance maps corresponding to the detection surface of the microsystem at three increasing deflection angles, i.e., 1, 2, and 3°. The semi-transparent circle represents the optical fiber connected to the detector, coinciding with that in size and position in the microsystem. (D) Representation of a variation in irradiance percentage with the deflection angle, according to the values obtained by TracePro when considering the model presented in (C).

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  Figure 2. Design and fabrication of the photonic microsystem. (A) Illustration of the design and the fabrication scheme for two-layer photonic microsystem, including (i) the lightguide-cantilever, (ii) the self-alignment elements, (iii) the PDMS rib-waveguide, (iv) the curved, (v) straight air cavities, and (vi) the air cavity in the second layer aligned with the ones in the first layer. The black dotted line in the image corresponds to the transversal section of the design illustrated in the fabrication protocol. An image of the final microsystem includes a white line corresponding to the scale of 1 mm. (B) Ray tracing simulations of a 3D model of the photonic microsystem illustrating the light that, after being coupled into the device, is confined into the lightguide-cantilever. The simulation shows the wide aperture angle of the lightguide-cantilever, fundamental for the sensing capacity of the system. (C) Ray tracing simulations of a 3D model of the photonic microsystem, this time illustrating only these rays that, after being coupled into the system, reach the collection optical fiber and the detector. Two black dotted lines are present in the image. The bottom one indicates the…

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  Figure 3. In vitro validation of optical myography. (A) Illustration of the in vitro set-up and protocol for validation of the mechanical sensing with the photonic microsystem. Microsystem is implemented in the pressure myograph and properties of the microvessel are evaluated after intraluminal pressure changes or after addition of vasoconstrictor phenylephrine (Phe) or vasodilator acetylcholine (ACh) at 70 mmHg intraluminal pressure. (B) Image of the in vitro set-up, with a magnification in the region where microvessel and microsystem have physical contact (blue arrow indicates the region). (C) Representation of the variation of light transmittance at 700 nm (T, from photonic microsystem) and arterial diameter (ad, from videomicroscope) over time after exposure to intraluminal pressure steps from 5 to 120 mmHg. (D) Variation of the optical myography recordings over time after application of three consecutive intraluminal pressure cycles. (E) Averaged results for changes in light transmittance and outer diameter magnitude with the intraluminal pressure with the applied pressure steps shown in (C). (F) Light transmittance and outer diameter changes in response to Phe (5 nM−1 μM). (G)…

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  Figure 4. In vivo analysis of isolated microvessels. (A) Image of the in vivo set-up, with a magnification in the region where microvessel and microsystem are in a physical contact (blue arrow indicates the region). (B) Illustration of the in vivo set-up and protocol for analysis of structure and function of the microvessel with the microsystem. Functional properties of the microvessel are evaluated assessing vasoconstriction with noradrenaline (NA) or vasodilatation with acetylcholine (ACh). A drawing depicted in this figure was obtained from the image repository Smart Servier Medical Art (https://smart.servier.com/). (C) Changes in light transmittance at 700 nm (T) and arterial diameter (ad, from videomicroscope) over time after application of 5 μM NA and the following application of 5 μM ACh. Periodic oscillations corresponding to vasomotion were clearly observed during contraction. (D) Magnification (×15) plot the region target in (C) illustrating the cantilever deflection caused by heartbeat and vasomotion (dash line). The average heart rate is calculated as the number of oscillations (beats) per minute. (E) Modulation of the vasomotion by addition of cyclopiazonic acid (CPA) or…

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  Figure 5. Analysis of intact microvessels in vivo. (A) Image of microsystem implemented in intact microvessels. (B) Image of the microsvessel before (left) and after (right) fat and connective tissue removal. Functional analysis of (C) intact and (D) isolated microvessels (after surrounding tissue removal) by vasoconstriction with noradrenaline (NA) or vasodilatation with acetylcholine (ACh). Microvessel function is assessed by following transmittance variation (in percentage) over time (n = 5).