Publications by authors named "Roya Sheybani"

15 Publications

  • Page 1 of 1

Development and validation of a cellular host response test as an early diagnostic for sepsis.

PLoS One 2021 15;16(4):e0246980. Epub 2021 Apr 15.

Louisiana State University Health Sciences Center, Baton Rouge, Louisiana, United States of America.

Sepsis must be diagnosed quickly to avoid morbidity and mortality. However, the clinical manifestations of sepsis are highly variable and emergency department (ED) clinicians often must make rapid, impactful decisions before laboratory results are known. We previously developed a technique that allows the measurement of the biophysical properties of white blood cells as they are stretched through a microfluidic channel. In this study we describe and validate the resultant output as a model and score-the IntelliSep Index (ISI)-that aids in the diagnosis of sepsis in patients with suspected or confirmed infection from a single blood draw performed at the time of ED presentation. By applying this technique to a high acuity cohort with a 23.5% sepsis incidence (n = 307), we defined specific metrics-the aspect ratio and visco-elastic inertial response-that are more sensitive than cell size or cell count in predicting disease severity. The final model was trained and cross-validated on the high acuity cohort, and the performance and generalizability of the model was evaluated on a separate low acuity cohort with a 6.4% sepsis incidence (n = 94) and healthy donors (n = 72). For easier clinical interpretation, the ISI is divided into three interpretation bands of Green, Yellow, and Red that correspond to increasing disease severity. The ISI agreed with the diagnosis established by retrospective physician adjudication, and accurately identified subjects with severe illness as measured by SOFA, APACHE-II, hospital-free days, and intensive care unit admission. Measured using routinely collected blood samples, with a short run-time and no requirement for patient or laboratory information, the ISI is well suited to aid ED clinicians in rapidly diagnosing sepsis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246980PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049231PMC
April 2021

Complementary sensors for rapid and sensitive detection of wound bacteria.

Annu Int Conf IEEE Eng Med Biol Soc 2016 Aug;2016:1902-1905

Dual sensors for timely wound bacterial infection detection through the measurement of pH and bacterial cell attachment were developed. A high sensitivity of -57.98 ± 7.08 mV/pH (pH 1-13; over 14 days) and a minimum detectable bacteria concentration of 103 CFU/mL was achieved for the pH and cell-based sensors, respectively. Sensors were capable of successfully monitoring growth of bacteria (Staphylococcus aureus and Pseudomonas aeruginosa) over time with and without antibiotics in simulated would fluid.
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http://dx.doi.org/10.1109/EMBC.2016.7591093DOI Listing
August 2016

Highly sensitive label-free dual sensor array for rapid detection of wound bacteria.

Biosens Bioelectron 2017 Jun 31;92:425-433. Epub 2016 Oct 31.

School of Engineering, Center for Biomedical Engineering, Institute for Molecular and Nanoscale Innovation, Brown University, Providence, RI 02912, United States. Electronic address:

Wound infections are a critical healthcare concern worldwide. Rapid and effective antibiotic treatments that can mitigate infection severity and prevent the spread of antibiotic resistance are contingent upon timely infection detection. In this work, dual electrochemical pH and cell-attachment sensor arrays were developed for the real-time spatial and temporal monitoring of potential wound infections. Biocompatible polymeric device coatings were integrated to stabilize the sensors and promote bacteria attachment while preventing non-specific cell and protein fouling. High sensitivity (bacteria concentration of 10 colony forming units (CFU)/mL and -88.1±6.3mV/pH over a pH range of 1-13) and stability over 14 days were achieved without the addition of biological recognition elements. The dual sensor array was demonstrated to successfully monitor the growth of both gram-positive (Staphylococcus aureus and Streptococcus pyogenes) and gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli) over time through lag and log growth phases and following antibiotic administration and in simulated shallow wounds conditions. The versatile fabrication methods utilized in sensor development, superior sensitivity, prolonged stability, and lack of non-specific sensor fouling may enable long-term in situ sensor array operation in low resource settings.
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http://dx.doi.org/10.1016/j.bios.2016.10.084DOI Listing
June 2017

A Wireless Implantable Micropump for Chronic Drug Infusion Against Cancer.

Sens Actuators A Phys 2016 Mar;239:18-25

Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, 1042 Downey Way, DRB-140, Los Angeles, CA 90089-1111, USA; Department of Electrical Engineering, Viterbi School of Engineering, University of Southern California, 3651 Watt Way, VHE-602, Los Angeles, CA 90089-0241, USA.

We present an implantable micropump with a miniature form factor and completely wireless operation that enables chronic drug administration intended for evaluation and development of cancer therapies in freely moving small research animals such as rodents. The low power electrolysis actuator avoids the need for heavy implantable batteries. The infusion system features a class E inductive powering system that provides on-demand activation of the pump as well as remote adjustment of the delivery regimen without animal handling. Micropump performance was demonstrated using a model anti-cancer application in which daily doses of 30 μL were supplied for several weeks with less than 6% variation in flow rate within a single pump and less than 8% variation across different pumps. Pumping under different back pressure, viscosity, and temperature conditions were investigated; parameters were chosen so as to mimic conditions. In benchtop tests under simulated conditions, micropumps provided consistent and reliable performance over a period of 30 days with less than 4% flow rate variation. The demonstrated prototype has potential to provide a practical solution for remote chronic administration of drugs to ambulatory small animals for research as well as drug discovery and development applications.
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http://dx.doi.org/10.1016/j.sna.2016.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4735729PMC
March 2016

Acceleration Techniques for Recombination of Gases in Electrolysis Microactuators with Nafion®-Coated Electrocatalyst.

Sens Actuators B Chem 2015 Dec;221:914-922

Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, 1042 Downey Way, DRB-140, Los Angeles, CA 90089-1111, USA ; Department of Electrical Engineering, Viterbi School of Engineering, University of Southern California, 3651 Watt Way, VHE-602, Los Angeles, CA 90089-0241, USA.

Recombination of electrolysis gases (oxidation of hydrogen and reduction of oxygen) is an important factor in operation efficiency of devices employing electrolysis such as actuators and also unitized regenerative fuel cells. Several methods of improving recombination speed and repeatability were developed for application to electrolysis microactuators with Nafion®-coated catalytic electrodes. Decreasing the electrolysis chamber volume increased the speed, consistency, and repeatability of the gas recombination rate. To further improve recombination performance, methods to increase the catalyst surface area, hydrophobicity, and availability were developed and evaluated. Of these, including in the electrolyte pyrolyzed-Nafion®-coated Pt segments contained in the actuator chamber accelerated recombination by increasing the catalyst surface area and decreasing the gas transport diffusion path. This approach also reduced variability in recombination encountered under varying actuator orientation (resulting in differing catalyst/gas bubble proximity) and increased the rate of recombination by 2.3 times across all actuator orientations. Repeatability of complete recombination for different generated gas volumes was studied through cycling.
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http://dx.doi.org/10.1016/j.snb.2015.07.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4522938PMC
December 2015

Wireless programmable electrochemical drug delivery micropump with fully integrated electrochemical dosing sensors.

Biomed Microdevices 2015 Aug;17(4):74

Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, 1042 Downey Way, DRB-140, Los Angeles, CA, 90089-1111, USA.

We present a fully integrated implantable electrolysis-based micropump with incorporated EI dosing sensors. Wireless powering and data telemetry (through amplitude and frequency modulation) were utilized to achieve variable flow control and a bi-directional data link with the sensors. Wireless infusion rate control (0.14-1.04 μL/min) and dose sensing (bolus resolution of 0.55-2 μL) were each calibrated separately with the final circuit architecture and then simultaneous wireless flow control and dose sensing were demonstrated. Recombination detection using the dosing system, as well as, effects of coil separation distance and misalignment in wireless power and data transfer were studied. A custom-made normally closed spring-loaded ball check valve was designed and incorporated at the reservoir outlet to prevent backflow of fluids as a result of the reverse pressure gradient caused by recombination of electrolysis gases. Successful delivery, infusion rate control, and dose sensing were achieved in simulated brain tissue.
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http://dx.doi.org/10.1007/s10544-015-9980-7DOI Listing
August 2015

MEMS: Enabled Drug Delivery Systems.

Adv Healthc Mater 2015 May 20;4(7):969-82. Epub 2015 Feb 20.

Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, 1042 Downey Way DRB-140, Los Angeles, CA, 90089-1111, USA.

Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed.
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http://dx.doi.org/10.1002/adhm.201400772DOI Listing
May 2015

On-demand wireless infusion rate control in an implantable micropump for patient-tailored treatment of chronic conditions.

Annu Int Conf IEEE Eng Med Biol Soc 2014 ;2014:882-5

Wireless infusion rate control and programmability for an implantable, low power, electrochemical micropump is presented. Flow rate control was achieved through adjustment of the wiper position of a current potentiometer in the wireless receiver (0.6-3.2 mA output current with a resolution of 0.2 mA per step). An off-the-shelf Bluetooth module and Basic Stamp microcontroller kit was used to initiate amplitude-shift keying (ASK) modulation of the inductive power signal. Accurate flow control of two model regimens was achieved on benchtop. Wireless transmission (power transfer and control) was not affected by simulated tissue material placed between the transmitter and receiver.
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http://dx.doi.org/10.1109/EMBC.2014.6943732DOI Listing
October 2016

Micro- and nano-fabricated implantable drug-delivery systems: current state and future perspectives.

Ther Deliv 2014 Nov;5(11):1167-70

Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.

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http://dx.doi.org/10.4155/tde.14.90DOI Listing
November 2014

Design, fabrication, and characterization of an electrochemically-based dose tracking system for closed-loop drug delivery.

Annu Int Conf IEEE Eng Med Biol Soc 2012 ;2012:519-22

Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089-1111, USA.

A real-time integrated electrochemically-based dose tracking system for closed-loop drug delivery is presented. Thin film Pt sensors were integrated in an electrolytic MEMS drug delivery pump to allow dose tracking via electrochemical impedance measurement. Measurement electrode placement and composition were investigated. A bolus resolution of 230 nL was demonstrated. The sensor was calibrated for use with water (low conductivity) and 1 × PBS (high conductivity), the selected model aqueous drugs. The impedance response is dependent on delivered volume and not affected by actuation parameters. A graphical user interface was created for real-time impedance based dose tracking and leakage/blockage detection in the system. Drift in the impedance response of an idle system after perturbation (actuation) were investigated and mitigated through the use of Pt wire electrodes as opposed to thin film electrodes.
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http://dx.doi.org/10.1109/EMBC.2012.6345982DOI Listing
September 2013

A MEMS electrochemical bellows actuator for fluid metering applications.

Biomed Microdevices 2013 Feb;15(1):37-48

Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, 1042 Downey Way, DRB-140, Los Angeles, CA 90089-1111, USA.

We present a high efficiency wireless MEMS electrochemical bellows actuator capable of rapid and repeatable delivery of boluses for fluid metering and drug delivery applications. Nafion®-coated Pt electrodes were combined with Parylene bellows filled with DI water to form the electrolysis-based actuator. The performance of actuators with several bellows configurations was compared for a range of applied currents (1-10 mA). Up to 75 boluses were delivered with an average pumping flow rate of 114.40 ± 1.63 μL/min. Recombination of gases into water, an important factor in repeatable and reliable actuation, was studied for uncoated and Nafion®-coated actuators. Real-time pressure measurements were conducted and the effects of temperature, physiological back pressure, and drug viscosity on delivery performance were investigated. Lastly, we present wireless powering of the actuator using a class D inductive powering system that allowed for repeatable delivery with less than 2 % variation in flow rate values.
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http://dx.doi.org/10.1007/s10544-012-9685-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755886PMC
February 2013

An implantable MEMS micropump system for drug delivery in small animals.

Biomed Microdevices 2012 Jun;14(3):483-96

Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, 1042 Downey Way, DRB-140, Los Angeles, CA 90089-1111, USA.

We present the first implantable drug delivery system for controlled timing and location of dosing in small animals. Current implantable drug delivery devices do not provide control over these factors nor are they feasible for implantation in research animals as small as mice. Our system utilizes an integrated electrolysis micropump, is refillable, has an inert drug reservoir for broad drug compatibility, and is capable of adjustment to the delivery regimen while implanted. Electrochemical impedance spectroscopy (EIS) was used for characterization of electrodes on glass substrate and a flexible Parylene substrate. Benchtop testing of the electrolysis actuator resulted in flow rates from 1 μL/min to 34 μL/min on glass substrate and up to 6.8 μL/min on Parylene substrate. The fully integrated system generated a flow rate of 4.72 ± 0.35 μL/min under applied constant current of 1.0 mA while maintaining a power consumption of only ~3 mW. Finally, we demonstrated in vivo application of the system for anti-cancer drug delivery in mice.
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http://dx.doi.org/10.1007/s10544-011-9625-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348997PMC
June 2012

A Parylene Bellows Electrochemical Actuator.

J Microelectromech Syst 2010 Jan;19(1):215-228

Department of Electrical Engineering, University of Southern California, Los Angeles, CA 90089 USA ( ).

We present the first electrochemical actuator with Parylene bellows for large-deflection operation. The bellows diaphragm was fabricated using a polyethylene-glycol-based sacrificial molding technique followed by coating in Parylene C. Bellows were mechanically characterized and integrated with a pair of interdigitated electrodes to form an electrochemical actuator that is suitable for low-power pumping of fluids. Pump performance (gas generation rate and pump efficiency) was optimized through a careful examination of geometrical factors. Overall, a maximum pump efficiency of 90% was achieved in the case of electroplated electrodes, and a deflection of over 1.5 mm was demonstrated. Real-time wireless operation was achieved. The complete fabrication process and the materials used in this actuator are bio-compatible, which makes it suitable for biological and medical applications.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035913PMC
http://dx.doi.org/10.1109/jmems.2009.2032670DOI Listing
January 2010

A low power, on demand electrothermal valve for wireless drug delivery applications.

Lab Chip 2010 Jan 19;10(1):101-10. Epub 2009 Oct 19.

Ming Hsieh Department of Electrical Engineering, University of Southern California, Los Angeles, CA 90089, USA.

We present a low power, on demand Parylene MEMS electrothermal valve. A novel Omega-shaped thermal resistive element requires low power (approximately mW) and enables rapid valve opening (approximately ms). Using both finite element analysis and valve opening experiments, a robust resistive element design for improved valve opening performance in water was obtained. In addition, a thermistor, as an inrush current limiter, was added into the valve circuit to provide variable current ramping. Wireless activation of the valve using RF inductive power transfer was demonstrated.
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http://dx.doi.org/10.1039/b910248eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134919PMC
January 2010

Implantable MEMS drug delivery pumps for small animal research.

Annu Int Conf IEEE Eng Med Biol Soc 2009 ;2009:6696-8

Departments of Biomedical and Electrical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089-1111, USA. ellis.meng@ usc.edu

Advanced devices capable of selective delivery of compounds to targeted tissues are lacking, especially in small animal research. Biomedical microelectromechanical systems (bioMEMS) are uniquely suited to this application through the combination of scalability and precise control of fluid handling. Polymer-based drug delivery components and pumps for acute and chronic delivery in small animals are discussed.
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http://dx.doi.org/10.1109/IEMBS.2009.5333284DOI Listing
March 2010