Biodegradable Piezoelectric Force Sensor Eli J. Curry and Thanh D. Nguyen Departments of Biomedical and Mechanical Engineering, University of Connecticut INTRODUCTION SIGNIFICANCE • Measuring vital physiological pressures is important for the following reasons: • Monitoring health status • Preventing the buildup of dangerous internal pressures in impaired organs • Compartment Syndrome • Meningitis • Glaucoma • Pressure sensors are often required to directly interface with native soft biological systems • Therefore the devices should be flexible and biodegradable to avoid an invasive removal surgery • Despite recent achievements in degradable electronic devices, there is still a tremendous need to develop a force sensor which: • Only relies on safe medical materials • Requires no complex fabrication process to provide accurate information on important bio-physiological forces • Here we present a new strategy for device fabrication using a piezoelectric poly-L-lactic acid (PLLA) polymer film to create a: • Biodegradable, Biocompatible, Piezoelectric Force Sensor • The sensor can precisely measure a wide range of pressures (0- 18 kPa) • Sustain a reliable performance for a period of 4 days in an aqueous environment • The sensor was implanted inside the abdominal cavity of a mouse to monitor the pressure of diaphragmatic contraction • The sensor can be integrated with tissues and organs, forming self-sensing bionic systems to enable many exciting applications in regenerative medicine, drug delivery, and medical devices OBJECTIVE AND DEVICE CONCEPT Figure 1. Biodegradable piezoelectric PLLA pressure sensor. a. Simplified schematic representing the biodegradable piezoelectric PLLA sensor. b. Optical image of a fabricated biodegradable piezoelectric PLLA sensor (5 mm x 5 mm and 200 µm thick). METHODS AND RESULTS • The sensor structure is as follows: • Two layers of piezoelectric PLLA • Molybdenum (Mo) electrodes • Encapsulating layers of polylactic acid (PLA) • All of these materials have been used in FDA-approved applications • Mo is used for implanted cardiovascular stents • PLA and PLLA are often used for bone screws and tissue scaffolds • The device dimensions are only 5 mm x 5 mm and 200 µm thick • This makes the sensor flexible • The sensor’s thickness can be reduced, making it even more flexible and facilitating device-integration with soft tissues and organs X-Ray Diffraction (XRD) Characterization of Piezoelectric PLLA • In order to make PLLA piezoelectric, two major material properties need to be improved: • Crystallinity • Molecular orientation of the polymer chains • This is done by simultaneous thermal annealing and mechanical stretching processes, respectively. Figure 2. Characterization of crystallinity and polymer chain orientation for processed PLLA. a. Results from one- dimensional X-ray diffraction (1D XRD) of stretched PLLA films with different draw ratios (DRs). The insert shows crystallinity percentage of the processed PLLA for different draw ratios, quantified from the 1D XRD spectrum. b. Two dimensional X- ray diffraction (2D XRD) images show polymer chain’s orientation of the stretched PLLA films with different draw ratios. Characteriz ation of PLLA Piezoelectric Performance Figure 3. Characterization of piezoelectric PLLA output from vibration and impact modes. a. Simplified schematics representing the vibration and impact methods used to characterize the PLLA. b. Voltage output from the treated PLLA with different draw ratios (DRs) under a vibration at 200 Hz. c. Voltage output from an untreated PLLA (red) and treated PLLA (black, DR = 6) under the same impact force. Characteriz ation of Biodegradable Piezoelectric Sensor Figure 4. Characterization of biodegradable piezoelectric PLLA sensor. a. Typical calibration curve generated by a PLLA sensor / charge amplifier circuit assembly. The insert shows typical output voltage signals from different input forces. b. Output signals from the biodegradable PLLA sensor (red) and a commercially-available piezoelectric quartz sensor (black) under the same applied force/pressure. c. Output voltages of the PLLA sensor under the same applied pressure at initial day and after 4 days in phosphate buffered solution at 37˚C. d. optical images showing the sensor at different days in the buffered solution at an accelerated-degradation temperature of 74˚C. In Vivo Force Measurement and Biocompatibility Test Figure 5. In vivo force measurement and biocompatibility test. a. Optical image illustrates the sensor and a mouse abdominal cavity with diapghramatic membrane. b. Surgical wound closed up by medical suture on abdomen of the mouse, which received an implanted PLLA sensor. c. Data shows the distinct force signals generated by the implanted sensor when the mouse was alive and under anesthesia (black), and when the mouse was euthanized by overdose of anesthetics (red). The insert diagram desribes the sensor attached to the bottom of mouse diaphgram inside the abdomen. (d-e) and (f-g) are histology images of subcutaneously- implanted PLLA sensors after 2 weeks and 4 weeks, respectively. (d) and (f) are histology stained by H&E (Hematoxylin and eosin) while (e) and (g) are histology stained by Masson’s Trichrome. Asterisks (*) show locations of the implanted sensors. All scale bars are 100 µm. CONCLUSION • Herein we present the first ever biodegradable piezoelectric force sensor for the monitoring of important physiologicalforces. • This sensor, only made of common biomedical materials, is a significant step forward for the field of implantable force sensors • Can be used for wireless monitoring of a variety of important physiological pressures such as: • Intra-articular pressure, • Intra-abdominal pressure • Intra-ocular pressure • Intra-cranial pressure • Continued improvements and applications of this device can have a major impact on the medicine of tomorrow. REFERENCES • EJ Curry, et al. Biodegradable Piezoelectric Force Sensor. (PNAS, 2017) • EJ Curry, et al. Biodegradable nanofiber-based piezoelectric transducer. (PNAS, 2020) ACKNOWLEDGEMENTS • Academic Plan Award (UConn), NIH Trailblazer Award (1R21EB024787-01, NIH), Hartford Engineering A Limb (HEAL, CT) project, NIH Grant 1R21AR075196-01
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Biodegradable Piezoelectric Force SensorEli J. Curry and Thanh D. Nguyen
Departments of Biomedical and Mechanical Engineering, University of Connecticut
INTRODUCTION
SIGNIFICANCE
• Measuring vital physiological pressures is important for the following reasons:• Monitoring health status• Preventing the buildup of dangerous internal pressures in impaired
organs• Compartment Syndrome• Meningitis• Glaucoma
• Pressure sensors are often required to directly interface with native softbiological systems
• Therefore the devices should be flexible and biodegradable to avoid aninvasive removal surgery
• Despite recent achievements in degradable electronic devices, there is still atremendous need to develop a force sensor which:
• Only relies on safe medical materials• Requires no complex fabrication process to provide accurate
information on important bio-physiological forces
• Here we present a new strategy for device fabrication using a piezoelectricpoly-L-lactic acid (PLLA) polymer film to create a:
• Biodegradable, Biocompatible, Piezoelectric Force Sensor• The sensor can precisely measure a wide range of pressures (0-
18 kPa)• Sustain a reliable performance for a period of 4 days in an
aqueous environment• The sensor was implanted inside the abdominal cavity of a
mouse to monitor the pressure of diaphragmatic contraction
• The sensor can be integrated with tissues and organs, forming self-sensingbionic systems to enable many exciting applications in regenerative medicine,drug delivery, and medical devices
OBJECTIVE AND DEVICE CONCEPT
Figure 1. Biodegradable piezoelectricPLLA pressure sensor. a. Simplifiedschematic representing the biodegradablepiezoelectric PLLA sensor. b. Optical imageof a fabricated biodegradable piezoelectricPLLA sensor (5 mm x 5 mm and 200 µmthick).
METHODS ANDRESULTS
• The sensor structure is as follows:• Two layers of piezoelectric
PLLA• Molybdenum (Mo) electrodes• Encapsulating layers of
polylactic acid (PLA)
• All of these materials have beenused in FDA-approved applications
• Mo is used for implantedcardiovascular stents
• PLA and PLLA are often usedfor bone screws and tissuescaffolds
• The device dimensions are only 5mm x 5 mm and 200 µm thick
• This makes the sensorflexible
• The sensor’s thickness canbe reduced, making it evenmore flexible and facilitatingdevice-integration with softtissues and organs
X-Ray Diffraction (XRD) Characterization of Piezoelectric PLLA• In order to make PLLA piezoelectric, two
major material properties need to beimproved:
• Crystallinity• Molecular orientation of the
polymer chains• This is done by simultaneous thermal
annealing and mechanical stretchingprocesses, respectively.
Figure 2. Characterization of crystallinity and polymerchain orientation for processed PLLA. a. Results from one-dimensional X-ray diffraction (1D XRD) of stretched PLLA filmswith different draw ratios (DRs). The insert shows crystallinitypercentage of the processed PLLA for different draw ratios,quantified from the 1D XRD spectrum. b. Two dimensional X-ray diffraction (2D XRD) images show polymer chain’sorientation of the stretched PLLA films with different drawratios.
Characterization of PLLA Piezoelectric Performance
Figure 3. Characterization of piezoelectric PLLAoutput from vibration and impact modes.a. Simplified schematics representing the vibration andimpact methods used to characterize the PLLA. b.Voltage output from the treated PLLA with different drawratios (DRs) under a vibration at 200 Hz. c. Voltageoutput from an untreated PLLA (red) and treated PLLA(black, DR = 6) under the same impact force.
Characterization of Biodegradable Piezoelectric Sensor
Figure 4. Characterization of biodegradable piezoelectric PLLA sensor. a. Typical calibration curvegenerated by a PLLA sensor / charge amplifier circuit assembly. The insert shows typical output voltagesignals from different input forces. b. Output signals from the biodegradable PLLA sensor (red) and acommercially-available piezoelectric quartz sensor (black) under the same applied force/pressure. c.Output voltages of the PLLA sensor under the same applied pressure at initial day and after 4 days inphosphate buffered solution at 37˚C. d. optical images showing the sensor at different days in thebuffered solution at an accelerated-degradation temperature of 74˚C.
In Vivo Force Measurement and Biocompatibility Test
Figure 5. In vivo force measurement andbiocompatibility test. a. Optical image illustrates thesensor and a mouse abdominal cavity withdiapghramatic membrane. b. Surgical wound closedup by medical suture on abdomen of the mouse, whichreceived an implanted PLLA sensor. c. Data shows thedistinct force signals generated by the implantedsensor when the mouse was alive and underanesthesia (black), and when the mouse waseuthanized by overdose of anesthetics (red). Theinsert diagram desribes the sensor attached to thebottom of mouse diaphgram inside the abdomen. (d-e)and (f-g) are histology images of subcutaneously-implanted PLLA sensors after 2 weeks and 4 weeks,respectively. (d) and (f) are histology stained by H&E(Hematoxylin and eosin) while (e) and (g) are histologystained by Masson’s Trichrome. Asterisks (*) showlocations of the implanted sensors. All scale bars are100 µm. CONCLUSION• Herein we present the first ever biodegradable piezoelectric force
sensor for the monitoring of important physiological forces.• This sensor, only made of common biomedical materials, is a
significant step forward for the field of implantable force sensors• Can be used for wireless monitoring of a variety of important
physiological pressures such as:• Intra-articular pressure,• Intra-abdominal pressure• Intra-ocular pressure• Intra-cranial pressure
• Continued improvements and applications of this device can have amajor impact on the medicine of tomorrow.
REFERENCES• EJ Curry, et al. Biodegradable Piezoelectric Force Sensor. (PNAS, 2017)• EJ Curry, et al. Biodegradable nanofiber-based piezoelectric transducer. (PNAS, 2020)
ACKNOWLEDGEMENTS • Academic Plan Award (UConn), NIH Trailblazer Award (1R21EB024787-01, NIH), Hartford
Engineering A Limb (HEAL, CT)project, NIH Grant 1R21AR075196-01
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