Optical Oxygen Sensor Patch Printed with Polystyrene Microparticles-based Ink on Flexible Substrate

Abstract

Optical oxygen sensors based on photoluminescence quenching have gained increasing attention as a superior method for continuous monitoring of oxygen in a growing number of applications. A simple and low-cost fabrication technique was developed to produce sensor arrays capable of two-dimensional oxygen tension measurement. Sensor patches were printed on polyvinylidene chloride film using an oxygen-sensitive ink cocktail, prepared by immobilizing Pt(II) mesotetra(pentafluorophenyl)porphine (PtTFPP) in monodispersed polystyrene microparticles. The dispersion media of the ink cocktail, high molecular weight polyvinyl pyrrolidone suspended in 50% ethanol (v/v in water), allowed adhesion promotion and compatibility with most common polymeric substrates. Ink phosphorescence intensity was found to vary primarily with fluorophore concentration and to a lesser extent with polystyrene particle size. The sensor performance was investigated as a function of oxygen concentrations employing two different techniques: a multi-frequency phase fluorometer and smart phone-based image acquisition. The printed sensor patch showed fast and repetitive response over 0-21% oxygen concentrations with high linearity (with R² >0.99) in a Stern-Volmer plot, and sensitivity of I₀/I₂₁ >1.55. The optical sensor response on a surface was investigated further using two-dimensional images which were captured and analyzed under different oxygen environment. Printed sensor patch along with imaging read-out technique make an ideal platform for early detection of surface wounds associated with tissue oxygen.

I. Introduction

OXYGEN concentration is one of the most crucial factors in medical diagnoses, industrial processes and environmental surveillance [1]-[6]. One exemplary area is the tissue oxygen monitoring to prevent ulcers caused by insufficient blood flow over a prolonged period that leads to ischemia and necrosis [7]. The multi-step wound healing process requires adequate oxygen supply at each step [8]. Since, oxygen cannot be stored in the cells, a constant supply of oxygen to the cells is necessary for wound healing as well as for the prevention of ulcer [9]. Hence, real-time monitoring of oxygen concentration is desirable [10].

The Clark electrochemistry-based method is the gold standard to measure partial pressure of oxygen (p_O2) [11]. This method incorporates the reduction of oxygen at a platinum cathode under an applied potential of typically 0.7 V. The current generated is related to p_O2. The major limitations of this method are that it consumes oxygen (which can alter the real oxygen level), associated with errors due to interference of the magnetic field and other deposited elements on the electrode, allowing measurements in only a small area [12]. Other available non-invasive, 2D imaging techniques based on radioisotopes (e.g. positron emission tomography) and magnetic resonance (e.g. magnetic resonance oximetry) are expensive and limited to some medical applications [13].

Currently, optical oxygen sensing technology is gaining much attention due to its easy applicability, high sensitivity, and no oxygen consumption [14], [15]. Optical oxygen sensors can be classified based on two operating methods: absorption and luminescence quenching. The absorption method uses the contrast between oxygenated and deoxygenated hemoglobin and serves as the basis for pulse oximetry; this useful clinical tool is applicable for determination of the oxygen level in blood, not in tissue [16].

The photoluminescence detection method is a non-invasive, rapid, real-time, sensitive technique for direct quantitation of oxygen level allowing point measurement and 2D surface monitoring [17]. These attributes make it a desirable technique for wide variety of applications.

The photoluminescence-based optical sensor works through an energy exchange mechanism [13], [18]. Luminescent molecules are excited to a higher energy state on stimulation with light waves and emit light of a longer wavelength when they return to the ground energy state. Dynamic collisions of molecular oxygen with excited molecules quench the luminescent emission, resulting in diminished luminescent intensity. Dynamic quenching is completely reversible and follows the Stern-Volmer equation (1), where I₀ and I are intensity of the fluorophore in absence and presence of oxygen respectively, K_sv is the Stern-Volmer constant, and p_O2 represents the partial pressure of oxygen.

$$\frac{{\mathrm{I}}_0}{\mathrm{I}}=1+{\mathrm{K}}_{\text{SV}}{\mathrm{P}}_{{\mathrm{O}}_2}$$ (1)

Metalloporphyrin-based fluorophores are popular due to their intense red phosphorescence with larger Stokes’ shift, longer lifetimes, higher chemical stability, etc. Halogen substitution further improves photostability. Fluorine substituted Pt(II) porphyrin (PtTFPP) has become the most frequently used fluorophore for intensity-based sensing systems [19], [20].

Online monitoring of oxygen either in gas or dissolved in liquid requires fluorophores firmly immobilized on a host material. The host polymer should be compatible and inert to fluorophores, provide long-term stability, and have optimum oxygen permeability and diffusion rate to achieve significant sensitivity. Silicone rubber is a commonly used FDA-approved polymer, but it has very high oxygen permeability that leads to a narrow linear dynamic range [21], [22]. Recently, polystyrene particles are widely used as host material to monitor cell metabolism and transcutaneous wound healing status [2], [23], [24]. Polystyrene is an inert, biocompatible material with optimum oxygen permeability in the physiological range of p_O2 (0-21% oxygen), resulting in single exponential calibration curve with a single quenching constant [25], [26]. Dissolving the fluorophore in a polymer/solvent mixture is the most common method of immobilizing it. Sometimes fluorophore dyes are also encapsulated in polymer particles to minimize dye leaching [21]. Polystyrene particles can be synthesized in nano- to micro-particle size and subsequently, luminescent dyes can be immobilized on them utilizing surface adsorption technique [4], [14], [27].

In this work, we report a luminescent polystyrene microparticle-based novel printable optical oxygen sensor ink. Optimum ink composition was determined to prepare a non-invasive, rapid and cost-effective sensor patches to measure oxygen over a surface. The overall sensor performance was characterized with a fluorometer and a smart phone for comparison toward a goal of tissue oxygen monitoring that is the critical signature of early surface wound development such as in ulcers and the subsequent healing process.

II. Materials and Methods

A. Chemicals

Styrene monomer (St, 99%), 2,2’-azobis(2-methylpropio nitrile) (AIBN, 98%) and two types of polyvinyl pyrrolidone (PVP) of molecular weight 360,000 and 40,000 were purchased from Sigma-Aldrich (St. Louis, MO, USA). The inhibitor from styrene was removed by passing it through the basic alumina column. Fluorophore Pt(II) meso-tetra (pentafluorophenyl)porphine (PtTFPP) was procured from Frontier Scientific (Logan, UT, USA). Solvents like tetrahydrofuran (99.9%) and toluene (99.5%) were obtained from Fischer Scientific (Pittsburgh, PA, USA) and ethyl alcohol (99.5%) from Acros Organics (Belgium, WI, USA). Polyvinylidene chloride film (PVDC, thickness 0.033 mm) was purchased from Goodfellow (Coraopolis, PA, USA).

B. Synthesis of Polystyrene Microparticles

Polystyrene microparticles were prepared using the free radical dispersion polymerization technique following the standard method [14], [28], [29]. The dispersing agent was prepared in a 3-neck round bottom flask by dissolving 300 mg of PVP (MW 40,000, 5 wt% of styrene) in 12 mL ultrapure water. 60 mg of AIBN (1 wt% of styrene) was dissolved in 6 g of purified styrene, and 38 mL of ethanol was then poured into the flask. The mixture was stirred at 70 °C for 24 h and after polymerization a white suspension was formed. The suspension was centrifuged at 5000 rpm for 15 min, the supernatant was discarded, and the suspension was washed twice. The particle size was measured using Zetasizer (Malvern Panalytical, Nano ZS90). Polystyrene particles were also synthesized using 450 mg and 600 mg of PVP (7.5 and 10 wt% of styrene) respectively to evaluate the effect of dispersing agent on the particle size. Solid particles were suspended in ethanol and particle concentration in the suspension was estimated after drying small portions under vacuum for 24 h.

C. Preparation of Luminescence Printing Ink

The oxygen-sensitive dye was first encapsulated in polystyrene particles. The suspension containing 100 mg PS particles was centrifuged and re-suspended in 5 mL of 50% ethanol (v/v in water). 1 mg of PtTFPP dye dissolved in 400 μL of THF was added to the mixture and vortexed for 1 min to allow the absorption of dye on the particles. This diffusion and entrapment method allows water-insoluble dyes to diffuse into the polymer matrix and get entrapped in the PS particles [23], [30]. Then the mixture was centrifuged, and the supernatant was discarded. The resultant dyed particles were again suspended in 50% ethanol and fluorescence scans were performed using a Fluorescence Spectroscope FS5 (Edinburgh Instruments Ltd.).

Printing ink was prepared by suspending dyed PS particles in suitable suspending media i.e., 50% ethanol containing 1 wt% PVP (MW 360,000). In the ink cocktail, PVP plays a dual role: dispersing agent in the liquid phase as well as adhesion promoter for the PS particles after the ink dries on the printed surface. Adhesion between printing ink and PVDC film was good as PVP is an excellent adhesion promoter with most organic materials[31], [32].

To evaluate the effect of particle size on intensity, 1 mg dye was loaded in 100 mg PS particles of three different sizes and suspended in 3 mL of suspending solution. To obtain maximum intensity as well as homogeneity of the patch, the dyed polystyrene particle concentration was varied in the ink cocktail. For this purpose 1 mg dye was loaded in 100 mg of PS particles (~1 μm size) and then PtTFPP/PS particles were suspended in 5 ml, 4 ml, 3 ml and 2 ml of suspending media respectively to increase the dye concentration from 0.2 to 0.5 mg/mL of the ink. For both above studies, 10 μL of the ink cocktail was deposited on PVDC film and luminescence intensity of the dried patches was compared.

D. Printing of Sensor Patch

Initially, a single dot sensor patch was fabricated by manual deposition of 10 μL of ink cocktail on PVDC film and allowed it to dry in a dark place. A sensor patch with an array of sensor dots was also printed on PVDC film using an automated micro-dispensing system suitable for particle-based ink. In the current study, a prototype printer was built using a Nordson EFD (Nordson Corporation, Westlake, Ohio, USA) automated droplet deposition system attached with an AxiDraw V3 2.5D Plotter (Evil Mad Scientist Laboratories, Sunnyvale, California, USA) and a house-built platform, shown in Fig. 1. The printer was a low-volume precision dispensing device operated by simple laboratory-scale pneumatic pressure. Thickness and size of the printed sensor dots was effectively controlled by dispensed volume of the ink and by means of the needle gauge attached to the printing head as well as the pneumatic pressure utilized. For potential self-calibration based on imaging, although not used in this study, some sensor dots were printed on the opposite side of the film (Fig. 2(a)) arranged in a quincunx pattern and always exposed to air (i.e., 21% oxygen) to serve as reference sensors [33]. These reference sensors will be utilized for compensating the intensity change over time. It is expected to minimize unpredictable intensity changes associated with light source instability, photo-degeneration, and/or dye leaching, where the zero oxygen environment for calibration is not available in the field. Instead, the traditional Stern-Volmer plot (I₀/I vs. % oxygen concentration) was used in this study for evaluating the sensor performance.

Fig. 1.

Prototype system to print senor patches.

Fig. 2.

(a) Cross-sectional schematic of a sensor patch mounted on calibration chamber and (b) camera setup attached to a smart phone for sensor imaging.

E. Sensor Film Readout Techniques

The luminescence response of the single-dot sensor patch was measured at different oxygen concentrations in gas phase by a multi-frequency phase fluorometer (MFPF 100, Tau Theta Instruments/Ocean Optics, Inc. Dunedin, FL, USA) attached with a built-in 470 nm LED for excitation.

An alternate image acquisition technique was also employed to determine luminescence response from the sensor array using a consumer-grade Android smart phone [34]. The sensor patch was illuminated using 24 405 nm LEDs arranged in a circular layout, magnified using a 10× macro camera lens assembly. The 600 nm optical filter (Roscolux color filter no. 25 orange-red, thickness 0.076 mm from Rosco Laboratories Inc., Stamford, CT, USA) was placed on top of the camera lens without covering 405 nm LEDs, so that only luminescent emission with wavelength longer than 600 nm to pass through the camera lens. The entire assembly was externally attached to the smart phone, as shown in Fig. 2(b). The 405 nm LEDs were chosen as they have the ideal wavelength to excite the maximum luminescence response. Fig. 3(a) to (c) show the luminescence response captured by the smart phone and saved in RAW format. RAW is the industry standard format for serializing image sensor data, i.e., as close as to the silicon sensor response as possible. Typically, the only processing of the sensor data would be based on the Bayer filter, which was used to decode sensor data to RGB image data. The images were further processed using MATLAB^® to obtain the luminescence sensor response.

Fig. 3.

Representative images (~1 mm diameter for each sensor) of the printed sensor patch with reference sensors arranged in a quincunx pattern exposed to air (top surface exposed to air) and working sensors (bottom side within calibration chamber) exposed to (a) 0%, (b) 4%, (c) 12% oxygen respectively.

For both the techniques, sensor patches were attached in a calibration chamber, as shown in Fig. 2(a). Pure nitrogen and oxygen gases were used, and flow rates were controlled by two mass flow controllers to achieve required oxygen concentration in the chamber. Phosphorescence intensity under different oxygen concentrations (0-21%) were measured and the Stern-Volmer plots were established. To minimize the variation in intensity due to photobleaching, each sensor was left exposed to ambient light at least 24 hours before use for initial photo-stabilization. It is known that photo-bleaching happens more substantially at the initial stage (typically called “stabilization” period).

III. Results and Discussion

A. Effect of Dispersing Agent on Polystyrene Particle Size

During dispersion polymerization, polystyrene particle size can be controlled by the amount of initiator, monomer, steric stabilizer, and polarity of the reaction media [28]. In this work, particle size was varied by choosing the steric stabilizer amount to alter the reaction condition. Polyvinyl pyrrolidone (PVP) proved to be a suitable steric stabilizer for dispersion polymerization [35]. Fig. 4(a) shows the variation of polystyrene particle size with PVP-to-styrene-monomer ratio in the reaction vessel. Resultant polystyrene particles were of three different sizes ranging from ~0.4 to 1.0 μm. PVP stabilizes polystyrene latex by adsorbing on the particle surface; therefore, average particle size reduces gradually with increasing PVP content. For a lower PVP amount, small polystyrene particles might be generated initially, which aggregated later to yield larger particles [29]. Size distribution of these three types of particles is shown in Fig. 4(b), which demonstrates that a narrow distribution resulted from lower particle size.

Fig. 4.

(a). Variation of particle size with respect to PVP-to-styrene-monomer ratio and (b) size distribution for three types of polystyrene particles.

B. Characterization of Dye-Loaded Polystyrene Particles

The dye diffusion and entrapment method allow homogenous distribution of fluorophore into the polystyrene particles without forming any covalent bond on its surface. Fig. 5(a) and (b) show the normalized absorption and emission spectra of the PtTFPP dye and dye encapsulated in PS (PtTFPP/PS) particles respectively suspended in 50% ethanol. To minimize the scattering effect from the suspended particles, cuvettes were placed at 45° inclined position in the cuvette holder of the Fluorescence Spectroscope FS5. Furthermore, spectra for the PtTFPP/PS particle suspension were plotted after subtracting blank PS particle spectra from them to remove the effect of scattering. Fig. 5(a) shows that PtTFPP dye has a Soret band at 394 nm followed by two Q bands at 508 nm and 540 nm, respectively. PtTFPP has emission maxima at 650 nm, as seen in Fig. 5(b). Absorption and emission maxima for PtTFPP/PS particles were similar to those of the PtTFPP dye alone, which signifies that absorption of PtTFPP on the PS particles surface did not alter the luminescence characteristics of the fluorophore.

Fig. 5.

(a) Absorption and (b) emission spectra of PtTFPP dye and PtTFPP/PS particle suspension.

C. Dependence of Luminescence Intensity on Polystyrene Particle Size and Dye Concentration

Three types of inks prepared with three different sizes of PS particles were tested for particle size - luminescence intensity correlation. Fig. 6(a) represents the fluorescence intensity of the sensor patches measured with MFPF 100; showing that intensity increased with respect to particle size in both 0% and 21% oxygen environments. This might be due to increased cross section with larger particle size, which leads to more fluorophore being excited. Our findings are in agreement with previous studies. Konemann et al. also reported an increase in fluorescence intensity with PS particle size on a single-particle scale and found that dry vs. wet state did not alter the intensity of dyed particles significantly [36]. According to Hill et al. [37] and Sivaprakasam et al. [38], fluorescence intensity of bioaerosol also increases with cross sectional area, and hence with particle size. It was found that sensitivity (I₀/I₂₁) of the sensors was not altered significantly with particle size, as also reported by Im et al. [28]. ~1 μm sized particles emitted maximum fluorescence intensity while maintaining overall homogeneity of the sensor patch. Therefore, this size was used for all the experiments.

Fig. 6.

Variation of luminescence intensity of sensor patch with (a) polystyrene particle size and (b) PtTFPP dye concentration.

The optimum fluorophore dye concentration was determined to exhibit proper emission intensity and printing compatibility. Effect of dye concentration study was carried out using a same dye amount (1 mg dye loaded in 100 mg of polystyrene particles) with varying amount of suspending media from 5 to 2 mL to achieve 0.2 to 0.5 mg/mL dye concentration, respectively. Printing ink with 0.33 mg/mL dye concentration was found optimum formulation for homogeneous printing. Intensity increased rather in a linear manner with dye concentrations for both 0% and 21% oxygen concentrations, as shown in Fig. 6(b). Sensitivity (I₀/I₂₁) was constant around 1.55 (up to 0.33 mg/mL), which increased to 1.82 (for 0.50 mg/mL). Although the dye concentration of 0.5 mg/mL and above might further improve the sensitivity, it could not be used for printing without agglomeration. Therefore, there was no need to investigate beyond 0.5 mg/mL of dye concentration due to the difficulty of printing.

The printed sensors were not solid films, but rather soft and brittle thick films due to the nature of sensor ink (i.e. polystyrene microparticle suspension). The common approach for measuring the thickness of solid films (e.g. stylus scanning) was therefore not appropriate for this case. The thickness and surface roughness of the printed sensor dots were observed using an optical microscope (Hirox, KH-8700). Measured thickness was approximately 40 μm with roughness of 5 μm.

D. Oxygen Sensing Performance

Inhomogeneous distribution of luminophores into polymer matrices generally affects intensity-based measurements. General aspects of the heterogeneity associated with luminophores and matrices are well documented [39]-[41]. Therefore, associated properties, e.g., permeability, solubility, and porosity are not investigated individually in this work. Overall effect of these parameters was studied through sensitivity curves and time responses, which provided enough information about the usability of this sensor patch for potential applications such as surface wound prevention.

Fig. 7(a) shows the phosphorescence intensity emitted by single sensor dots when excited with 470 nm light at different oxygen concentration, measured with MFPF 100. Phosphorescence intensity decreased significantly with increase in oxygen concentration represented by an increase of I_o/I in the associated the Stern-Volmer plot of Fig. 7(b). Fig. 8 shows the Stern-Volmer plot for an array of sensors excited with 405 nm light and phosphorescence intensity measured using the image acquisition technique. Each datapoint represents the average of all working sensors in images of four sensor patches. Effect of heterogeneous distribution of luminophores into polymer matrix was prominent in Stern-Volmer plots shown in Fig. 7(b) and 8, which were best-fitted by two-site model. Both readout techniques reported slightly different quenching constants for two linear responses up to 21% oxygen, suitable for most of the common clinical and environmental applications. I₀/I₂₁ was used as the measure of sensor sensitivity, where I₀ and I₂₁ represents the phosphorescence intensity of the sensors exposed to 0% and 21% oxygen respectively. Sensitivity between 0-21% obtained for the sensor array was 1.79, which was higher than the sensitivity of single sensor dots, i.e., 1.55. This lower sensitivity was expected since sensor dots were excited with 470 nm light (the only wavelength available from the built-in LED of MFPF 100), whereas the sensor array was illuminated with 405 nm light, which is much closer to the Soret band of the PtTFPP dye. The sensor response was fast and reproducible with relative standard deviation of less than 1.5%. Reflection of optical signals at the interface between PVDC film and sensor ink may exist. However, this reflective artifact, if any, are common to all sensors with different dye concentrations and will be largely eliminated by the ratiometric (I₀/I) Stern-Volmer plot as shown in Fig. 7(b).

Fig. 7.

(a) Time response of luminescence intensity at 0, 4, 8, 12, 16 and 21% oxygen level and (b) Stern-Volmer plot of single sensor dot measured using MFPF 100 with 470 nm excitation (n: 4 and bar: SD).

Fig. 8.

Stern-Volmer plot of sensor array measured using the smart phone camera with 405 nm light excitation (n: 80 and bar: SD).

Since the sensor patches will be utilized for rapid screening of incipient skin wounds, it would be more rational to check whether this sensor could measure tissue oxygen in the physiological range. Oxygen level at nominal healthy tissue area is typically 70-80 mmHg (equivalent to approximately 10%), while the incipient ulcer area with poor oxygen circulation has lower than 40 mmHg (equivalent to ~5.3%) [42]-[44]. Stern-Volmer plots (Fig. 7 and 8) showed that the sensor can clearly discriminate this difference and proved the feasibility for future target applications of early detection and rapid screening of incipient ulcers.

Fig. 9 represents the operational stability of the sensor patch excited with 470 nm light. It was observed that the sensor response was very stable and reproducible when switching between fully oxygenated to fully deoxygenated atmosphere. Response time and recovery time of the sensor were evaluated based on t₉₅ i.e. time required to achieve 95% of the total intensity change when switching between oxygen and nitrogen environments [14], [15]. Response time of the sensor to fully oxygenated condition was 4 s, whereas recovery time to fully deoxygenated condition was 20 s. The short response time makes it suitable for rapid detection of gaseous oxygen concentration in many practical applications.

Fig. 9.

Short-term stability and reversibility of single sensor dot measured using MFPF 100 when switching alternately between 100% nitrogen and 100% oxygen environment.

One potential application of this disposable sensor patch (e.g. 2 days) is the monitoring of transcutaneous oxygen in patients with minimal mobility lying on bed. This usage assumes an environment with very limited interference and variation, such as stable temperature close to the body temperature and stable skin humidity by perspiration typically in supine position. To minimize the effect of humidity and instability caused by fluorophore leaching from the sensor, the printed side of sensor was laminated with a polyethylene film (PE, thickness 0.025 mm from Poly-America, Grand Prairie, TX, USA), PE is known to have a high oxygen permeability with low water vapor transmission [45], [46]. The PE-laminated sensor patch was dipped into a 20 mL glass vial with a 10 mL D.I. water in it. It was placed in an incubator with a set temperature of 37 °C. Sensor patch was taken out from water at day 0, 3, 4 and 7 and its luminescence intensity was checked at 21% gaseous oxygen using MFPF 100, shown in Fig. 10. There was a gradual decrease of intensity during a week, which only showed a typical trend of intensity decrease of luminescence-based sensors over time. This can be compensated by the self-calibration imaging procedure as mentioned previously for real world application.

Fig. 10.

Stability of luminescence intensity of an encapsulated sensor patch at 37 °C in a wet environment.

IV. Conclusion

An optical oxygen sensor patch was fabricated using a PtTFPP fluorophore immobilized in polystyrene microparticle-based ink. Polystyrene particle size and its distribution were decreased with higher amount of low molecular weight polyvinyl pyrrolidone, which served as a steric stabilizer in polymerization of styrene. Phosphorescence intensity was found to be increased with fluorophore concentration and polystyrene particle size without any notable change of the sensor performance.

A prototype printing technique was developed suitable to print particle-based ink. An Android smart phone-based image acquisition technique was also established to quantify the phosphorescence intensity response as a function of oxygen concentration.

Printed sensor patches along with imaging read-out technique made the system suitable for simple, cost-effective monitoring of oxygen on a surface. Wide dynamic linear range (0-21% oxygen) of the sensors covers the physiological range.

Future research will determine potential usefulness of the sensor patches in clinical applications, especially for early detection and rapid screening of incipient skin wound (e.g. pressure ulcer) patients lying on bed with minimal mobility by monitoring oxygen over skin surface. It is expected that the proposed sensor is an ideal platform for early detection and timely intervention of surface wounds associated with tissue oxygen.

Biography

Mousumi Bose received the B.S. degrees in chemistry, and polymer science and technology from University of Calcutta, Kolkata, West Bengal, India in 2008 and 2011, respectively. She received the M.S. degree in polymer science and technology from Indian Institute of Technology Delhi, New Delhi, India in 2013. She received the PhD degree in chemistry from Missouri University of Science and Technology, Rolla, MO, USA in 2021. Her field of interests include polymer chemistry and analytical chemistry.

Jason Hagerty received the B.S degrees in computer science, computer engineering, and M.S degree from Missouri University of Science and Technology, Rolla, MO, USA in 2000, 2011, 2016, respectively. He is currently completing the PhD at Missouri University of Science and Technology. His field of interests include computer vision, medical imaging, and machine learning. He has been published in several peer reviewed journals and a recipient of the Brian J. Blaha Memorial Scholarship in 2016.

Jason Boes received the B.S. degree in chemistry from Missouri University of Science and Technology, Rolla, MO, USA in 2020. He is currently pursuing the Ph.D. degree in analytical chemistry from Colorado State University, Fort Collins, CO, USA. From 2017 to 2020 he was a Research Assistant with the lab of Dr. Paul Nam, Missouri University of Science and Technology, Rolla, MO, USA. His research interests include the practical application of sensing materials for biomedical analysis, low-cost sensing device fabrication, and sensing molecule synthesis.

Change-Soo Kim received the B.S., M.S., and Ph.D. degrees in electronic and electrical engineering from Kyungpook National University, Daegu, South Korea in 1989, 1991, and 1997, respectively.

As a Research Associate at the Sensor Technology Research Center, South Korea, he was involved in various research projects and commercial developments of microelectrochemical sensors and systems for monitoring gases, electrolytes, and biomolecules. At the Biomedical Microsensors Laboratory at North Carolina State University, Raleigh, and the Experimental Cardiology group, University of North Carolina at Chapel Hill, he conducted postdoctoral research on intelligent biochemical sensors, implantable device platforms, and cardiac biopotential recording with micromachined probes. He joined the Missouri University of Science and Technology (formerly University of Missouri-Rolla) in 2002 as an Assistant Professor of Electrical & Computer Engineering. Now he is a Professor with research interests including microsystem technologies and novel applications of microsystems to medical, biological and environmental engineering.

Dr. Kim served as principal investigator of many federal grants funded by NASA, NSF, NIH and USDA including his NSF CAREER award. He is a senior member of IEEE and serving as an Associate Editor of IEEE Sensors Journal.

William V. Stoecker received the B.S. degree in mathematics from California Institute of Technology, Pasadena, CA, USA in 1968, the M.S. degree in systems science from University of California, Los Angeles, CA, USA in 1971, and the M.D. from the University of Missouri, Columbia, MO, USA in 1977.

He is the editor of one book and co-author of more than 100 articles on medical imaging and medical informatics. He holds six USA and foreign patents. He is a practicing dermatologist.

Dr. Stoecker’s awards include the Meggers Project Award of the American Institute of Physics for the improvement of high school physics teaching and the American Society for Clinical Laboratory Science Research Award for best paper, 2009.

Paul Nam received the B.S. degree in chemistry from University of Hawaii, Honolulu, HI, USA in 1985. He received the M.S. and Ph.D. degrees in analytical chemistry from University of Missouri, Columbia, MO, USA in 1988 and 1991, respectively.

He is currently an Associate Professor of chemistry at Missouri University of Science and Technology, Rolla, MO, USA and has extensive experience in the areas of analytical and environmental chemistry. He is the author of more than 80 articles and 7 inventions. His research interests include the development of advanced analytical methods and instruments for the sampling, separation, detection, identification, and quantification of chemicals of biological and environmental interests.