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Bioresorbable optical sensor systems for monitoring of intracranial pressure and temperature

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Science Advances  05 Jul 2019:
Vol. 5, no. 7, eaaw1899
DOI: 10.1126/sciadv.aaw1899
  • Fig. 1 Materials and designs for bioresorbable FPI-based pressure and temperature sensors.

    (A) Schematic illustration of a bioresorbable FPI pressure and temperature sensor composed of a thermally grown silicon dioxide (t-SiO2) encapsulation layer, a Si NM, amorphous silica adhesion layer, and a silicon slab. The layers of t-SiO2 and Si NM serve as pressure-sensitive diaphragms that seal an air chamber formed by bonding with a silicon slab with a feature of relief etched onto its surface. The bottom image shows a cross-sectional view of a sensor integrated with two optical fibers that deliver light to diaphragm and nondiaphragm regions of the device, thereby enabling pressure and temperature sensing, respectively. (B) Photograph of a device placed on an adult brain model. The inset shows a magnified view. (C) Optical micrograph of the top diaphragm. (D) Optical spectra collected from a bioresorbable FPI pressure sensor immersed in PBS (pH 7.4) at room temperature under different pressures. The FP resonance peak associated with the air cavity shifts to the blue with increasing pressure. (E) 3D-FEA of the vertical displacement of the diaphragm along the midsection (red dotted line) at different pressures. (F) CEM simulations of optical spectra obtained at different displacements of the diaphragm. (G) Calibration curve for the FPI pressure sensor (red) compared with simulation results (blue) obtained in (C) and (F). (H) Optical spectra collected from a bioresorbable FPI temperature sensor immersed in PBS at varying temperatures. The FP resonance peak associated with silicon shifts to the red with increasing temperature. (I) Calibration curve for the FPI temperature sensor (red) compared with optical simulation results (blue). Circles and error bars in (G) and (I) indicate means ± SEM for three measurements.

  • Fig. 2 Materials and designs for bioresorbable PC microcavity-based pressure and temperature sensors.

    (A) Schematic illustration of a bioresorbable PC microcavity pressure and temperature sensor, based on a PC structure fabricated in a Si NM, which, together with layers of t-SiO2 for encapsulation, constitutes the diaphragm. The diaphragm seals an air cavity formed by bonding to a silicon substrate with a feature of relief etched into its surface. A layer of amorphous silica serves as an adhesion layer. A free-space detection setup couples light to the top surface of the device. Light delivered to the diaphragm and nondiaphragm regions of the device enables pressure and temperature sensing, respectively. (B) SEM image of PC structure (r = 85 nm, a = 1 μm) fabricated in the Si device layer of an SOI wafer by electron beam lithography. (C) Image of the diaphragm region of the device, illustrating the alignment of the PC cavity array (300 μm by 300 μm; yellow box) in the diaphragm over the trench etched on the silicon substrate (250 μm by 250 μm; white box). (D) Optical spectra collected from the PC pressure sensor placed in air at room temperature under different pressures. The PC resonance peak shifts to the red with increasing pressure. (E) 3D-FEA simulation of the average lattice constant (over the area of a 150-μm-diameter circle) at different pressures. (F) CEM simulation of the shift in the peak wavelength induced by changes in the lattice constant. (G) Calibration curve for the bioresorbable PC pressure sensor (red) compared with simulation data (blue) obtained in (E) and (F). (H) Optical spectra obtained from the PC temperature sensor in air at different temperatures. (I) Calibration curve for the bioresorbable PC temperature sensor (red) compared with optical simulation data (blue). Circles and error bars in (G) and (I) indicate means ± SEM for three measurements.

  • Fig. 3 Bioresorbable interfaces to the optical sensors.

    (A) Schematic illustration of the setup used for spectral analysis of bioresorbable FPI sensors. FC, ferrule connector; APC, angled physical contact. (B) Photograph of a PLGA fiber [diameter (d), ~200 μm] formed at the tip of a commercial SMF. (C) Photograph of a PLGA fiber aligned and fixed to the bottom diaphragm of a bioresorbable FPI pressure sensor. The bioresorbable glue holds the parts together. (D) FP resonance signals collected at different stages of the process of integrating the fiber with the surface of the sensor. The steps involve aligning the fiber tip to a non–air cavity region of the device (noncavity; black) at a perpendicular incidence and minimizing the distance between the tip and the device, laterally repositioning the fiber to align the tip close to the center region of the diaphragm, applying and curing the bioresorbable glue (on-cavity and glued; red), releasing the device from the water-soluble crystal bond by heating the carrier wafer (released; blue), and removing the residual crystal bond by dipping in warm water.

  • Fig. 4 Kinetics of dissolution and histological studies of bioresorbable optical sensors and fibers.

    (A) Optical micrographs at various stages of accelerated dissolution of a bioresorbable FPI sensor due to immersion in PBS (pH 7.4) at 95°C. (B) Schematic illustration of the setup used for the dissolution experiment in (A). (C) Pressure calibration curves obtained from a bioresorbable FPI pressure sensor (t-SiO2 thickness, 1 μm; air chamber thickness, 100 μm), integrated with a commercial optical fiber, soaked in PBS at 37°C for 8 days. The minimal changes in pressure sensitivity provide evidence for the effectiveness of t-SiO2 as a biofluid barrier. (D) Loss of transmission efficiency of the PLGA fiber over time due to immersion in PBS at 37°C. Circles and error bars indicate means ± SEM for four measurements. (E) Representative histological results of the brain, heart, kidney, liver, lung, and spleen organs explanted from a control mouse and a mouse with a bioresorbable FPI sensor implanted in the brain for 5 weeks. The results indicate an absence of abnormalities such as necrosis or inflammation.

  • Fig. 5 Acute monitoring of ICT and ICP in rats.

    (A) Photograph of a bioresorbable FPI sensor implanted in the intracranial space of a rat for monitoring ICT and ICP. A thin film of PLGA, with a hole in the middle for the fiber, and bioresorbable glue seal the cranial defect to form an airtight environment for accurate pressure sensing. A clinical fiber-optic ICP monitor, implanted nearby, provides reference data. (B) Cross-sectional schematic illustration of the device setup during animal testing. Cutting through the dura and exposing the device to CSF allows assessment of the ICP. (C and D) Optical spectra and pressure calibration curve obtained from a bioresorbable FPI pressure sensor, calibrated against the clinical ICP monitor. Contracting the flank of the rat temporarily raises the ICP by up to ~10 mmHg from the initial level. (E and F) Optical spectra and temperature calibration curve obtained from a bioresorbable FPI temperature sensor, calibrated against a commercial thermistor implanted nearby. The electrical heating blanket wrapped around the body of the rat gradually increased the ICT. (Photo credit for part A: Jiho Shin, University of Illinois at Urbana-Champaign.)

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/5/7/eaaw1899/DC1

    Note S1. Design considerations for FP pressure sensor.

    Note S2. Definition and calculation of device sensitivity and accuracy.

    Note S3. Temperature dependence of pressure sensor response.

    Note S4. Calculation of FPI temperature sensor sensitivity.

    Note S5. Comparison of reflection spectra of FPI and PC sensors.

    Note S6. Scalability and yield of bioresorbable PC sensor fabrication process.

    Note S7. Modal mismatch and noise in single mode–to–PLGA composite fiber.

    Note S8. Pressure and temperature cross-talk during in vivo measurement.

    Fig. S1. Schematic illustrations of steps for fabricating bioresorbable FPI pressure and temperature sensors.

    Fig. S2. Calculations of free spectral ranges and design optimization of bioresorbable FPI pressure sensors.

    Fig. S3. In vitro setup for calibrating the response of the bioresorbable FPI pressure sensor.

    Fig. S4. Effects of temperature on the response of a bioresorbable FPI pressure sensor.

    Fig. S5. Full temperature calibration curves for a bioresorbable FPI temperature sensor.

    Fig. S6. Schematic illustrations of fabrication procedures for bioresorbable PC cavity-based pressure and temperature sensors.

    Fig. S7. Free-space detection setup for testing bioresorbable PC-based pressure and temperature sensors.

    Fig. S8. Optical properties of bioresorbable PC sensors and PLGA fiber.

    Fig. S9. In vitro dissolution of a bioresorbable optical sensor.

    Fig. S10. Simultaneous recordings of a rat’s ICP and ICT during flank contract/release experiment using reference pressure and temperature sensors.

  • Supplementary Materials

    This PDF file includes:

    • Note S1. Design considerations for FP pressure sensor.
    • Note S2. Definition and calculation of device sensitivity and accuracy.
    • Note S3. Temperature dependence of pressure sensor response.
    • Note S4. Calculation of FPI temperature sensor sensitivity.
    • Note S5. Comparison of reflection spectra of FPI and PC sensors.
    • Note S6. Scalability and yield of bioresorbable PC sensor fabrication process.
    • Note S7. Modal mismatch and noise in single mode–to–PLGA composite fiber.
    • Note S8. Pressure and temperature cross-talk during in vivo measurement.
    • Fig. S1. Schematic illustrations of steps for fabricating bioresorbable FPI pressure and temperature sensors.
    • Fig. S2. Calculations of free spectral ranges and design optimization of bioresorbable FPI pressure sensors.
    • Fig. S3. In vitro setup for calibrating the response of the bioresorbable FPI pressure sensor.
    • Fig. S4. Effects of temperature on the response of a bioresorbable FPI pressure sensor.
    • Fig. S5. Full temperature calibration curves for a bioresorbable FPI temperature sensor.
    • Fig. S6. Schematic illustrations of fabrication procedures for bioresorbable PC cavity-based pressure and temperature sensors.
    • Fig. S7. Free-space detection setup for testing bioresorbable PC-based pressure and temperature sensors.
    • Fig. S8. Optical properties of bioresorbable PC sensors and PLGA fiber.
    • Fig. S9. In vitro dissolution of a bioresorbable optical sensor.
    • Fig. S10. Simultaneous recordings of a rat’s ICP and ICT during flank contract/release experiment using reference pressure and temperature sensors.

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