SYSTEM, METHOD AND APPARATUS FOR AN AMORPHOUS IRIDIUM OXIDE

FILM PH SENSOR

Field of Invention The present invention relates in general to the field of sensors, and more particularly to an amorphous iridium oxide film pH sensor.

Background Art pH sensors are used in clinics, laboratories and industrial factories since many biological and chemical reaction mechanisms are pH dependent. Conventional glass-type electrodes have been widely used; however, they still have certain disadvantages in specific applications. The glass rod sensor configuration is difficult to use for in vivo biomedical, clinical or food monitoring applications due to the brittleness of glass, size limitations and the lack of deformability. To achieve small sizes and robust design, ion-sensitive field-effect transistor (iSFET) pH sensors [1-5], optical fiber pH sensors [1, 6-11], hydrogel film pH sensors [12-14], and solid sate pH sensors [1, 15-18] have been proposed. iSFET sensors have power consumption concerns due to the field-effect transistor (FET) operational requirements [19]. Hydrogel film pH sensors utilize the physical properties of the pH-response swelling and shrinking polymer to measure resistance changes [12]. The sensor structure design and polymer layer fabrication process can be complicated and expensive [13]. Optical pH sensors also have power consumption issues due to the use of light sources. The system including optical devices could be expensive and unsuitable for implantation [1, 7-8, 10-11].

Various solid-state metal oxides have been investigated for pH sensing electrodes [1, 15] including PtO ₂ , IrO _x , RuO ₂ , OsO ₂ , Ta ₂ Os, RhO ₂ , TiO ₂ and SnO ₂ as the pH sensing films. The pH sensitivity, selectivity, working range, and hysteresis indicate sensing performance. IrO _x , Ruθ ₂ and SnO ₂ have been demonstrated with more advantages in sensor performance for various applications [22]. RuO ₂ [18, 20] and SnO ₂ [21] show near Nernstian responses in wide pH ranges. However, SnO ₂ and RuO ₂ presented hysteresis and drift problems leading to potential calibration issues and unstable responses [20, 21]. Iridium oxide film (IROF) has performed outstanding stability over wide pH rages, rapid responses, less hysteresis and high durability, which have also been demonstrated at high temperature up to 25O ⁰ C [23].

There are different fabrication methods for IROF including sputtering deposition [23, 24], electrochemical deposition [25-29], thermal oxidation [23], and sol-gel [30-32] processes. The sputtering iridium oxide film (SIROF) deposition process is costly due to the target cost.

The oxygen and argon pressure ratios, position of the target, deposition rate, and RF powers during the fabrication processes all affect the pH sensing parameters such as potential drifts and redox interference [22]. Anodic electrochemical deposition presents an economical way for iridium oxide thin film fabrication. The anodic iridium oxide thin film (AIROF) process is based on electrolysis of a solution containing iridium complexes. The iridium tetrachloride compound has been widely used as a deposition agent [26-29] such as the commonly used Yamanaka solution [26]. The pH value of the deposition solution, solution temperature and current density control affect the deposition efficiency [26-29]. A precise power supply system as potentiostate is required in the electro-deposition process for thickness and film quality control. For thermal oxidation process, it requires a high temperature ranging from 500 to 800 ⁰ C [17, 22]. The film made by thermal oxidation can be thicker than the AIROF with more stable potentials [22, 23]. However, the film surface has a tendency to crack after the high temperature treatment. The adhesion property of the cracked film then becomes an issue. The high temperature treatment also becomes a limitation during sensor fabrication, especially for the use of polymer and photoresist, which often can not survive at a temperature above 200 ⁰ C. The sol-gel IROF deposition process has been demonstrated [32] with dip coating [32, 33] and heat treatment [31, 32] procedures. Sol-gel deposition provides a simpler and economical fabrication approach.

There is, therefore, a need for a cost efficient, simpler fabrication and lower power consumption, a metal-oxide pH sensor with deformability on a flexible substrate.

Summary of the Invention

The present invention provides a sol-gel process to make IROF pH sensor arrays on flexible polyimide substrates. An amorphous and uniform IROF was formed with 300 ⁰ C thermal oxidation. Our IROF pH sensor provided good stability with less drifts, high selectivity, fast response, reversibility with low power consumption advantages along with the simpler and potentially lower cost fabrication processes. With these features, our sensors could be used for in vivo biomedical [34, 35], biological [36, 37], clinical [38-40], food monitoring [41, 42] and lubricant applications [43].

Both iridium oxide sensing films and Ag/ AgCl reference electrodes were formed on a polyimide flexible substrate by sol-gel, dip-coating and thermal oxidation processes. Fabrication, characterization, and dynamic test results of a deformable potentiometric pH electrode were presented. The IrO _x pH sensors exhibited promising sensing performance with a super-Nernstian response of sensitivity between 69.6 and 71.6 mV/pH in the pH range from 1.9 to 12 at 25 ⁰ C. A response time was obtained at less than 7 seconds. The pH electrodes showed high selectivity and reversibility in different acid and alkaline solutions. The deformable pH electrodes provide the advantage of accommodating sensors in small spaces or conform to curved surfaces. Our deformable pH sensor array responded with distinct potentials to various pH values at different positions inside a 1.5-cm diameter tube.

The present invention provides a pH sensing apparatus that includes a flexible polymer substrate, one or more amorphous iridium oxide film sensor electrodes disposed on the flexible polymer substrate, and a reference electrode corresponding to each amorphous iridium oxide film sensor electrode. Each reference electrode is disposed on the flexible polymer substrate in close proximity to the corresponding amorphous iridium oxide film sensor electrode. A first electrical contact pad corresponding to each amorphous iridium oxide film sensor electrode is disposed on the flexible polymer substrate and electrically connected to the corresponding amorphous iridium oxide sensor. A second electrical contact pad corresponding to each reference electrode is disposed on the flexible polymer substrate and electrically connected to the corresponding reference electrode. The amorphous iridium oxide film sensor electrodes provide a potential in reference to the reference electrodes that varies according to a pH of a substance contacting the amorphous iridium oxide film sensor electrodes and the reference electrodes.

In addition, the present invention provides a method for fabrication one or more pH sensors by depositing a chromium layer and a gold layer on a flexible polymer substrate to define a sensor electrode and a first electrical contact pad, depositing a sacrificial layer on the first electrical contact pad and the flexible polymer substrate, coating the sacrificial layer and the sensor electrode with an iridium oxide thin film, heating the sensor electrode to form an amorphous iridium oxide sensor electrode, removing the sacrificial layer, depositing a chromium layer, a platinum layer and a silver layer on the flexible polymer substrate to define a reference electrode and a second electrical pad, and electroplating the silver layer.

The present invention also provides a device for detecting spoilage in a food that includes a biocompatible pH sensing apparatus for physical contact with the food. The pH sensing apparatus includes a flexible polymer substrate, one or more amorphous iridium oxide film

sensor electrodes disposed on the flexible polymer substrate, and a reference electrode corresponding to each amorphous iridium oxide film sensor electrode. Each reference electrode is disposed on the flexible polymer substrate in close proximity to the corresponding amorphous iridium oxide film sensor electrode. A first electrical contact pad corresponding to each amorphous iridium oxide film sensor electrode is disposed on the flexible polymer substrate and electrically connected to the corresponding amorphous iridium oxide sensor. A second electrical contact pad corresponding to each reference electrode is disposed on the flexible polymer substrate and electrically connected to the corresponding reference electrode. The amorphous iridium oxide film sensor electrodes provide a potential in reference to the reference electrodes that varies according to a pH of the food contacting the amorphous iridium oxide film sensor electrodes and the reference electrodes. A passive radio frequency identification chip is electrically connected to the first and second electrical contact pads. A tag antenna electrically connected to the passive radio frequency identification chip. The present invention also provides a system for detecting spoilage in a food by adding a radio frequency identification reader comprising a computer connected to an antenna.

Moreover, the present invention provides a bandage for detecting a condition of a wound that includes a wound dressing material and a biocompatible pH sensing apparatus attached to the wound dressing material for physical contact with the wound. The pH sensing apparatus includes a flexible polymer substrate, one or more amorphous iridium oxide film sensor electrodes disposed on the flexible polymer substrate, and a reference electrode corresponding to each amorphous iridium oxide film sensor electrode. Each reference electrode is disposed on the flexible polymer substrate in close proximity to the corresponding amorphous iridium oxide film sensor electrode. A first electrical contact pad corresponding to each amorphous iridium oxide film sensor electrode is disposed on the flexible polymer substrate and electrically connected to the corresponding amorphous iridium oxide sensor. A second electrical contact pad corresponding to each reference electrode is disposed on the flexible polymer substrate and electrically connected to the corresponding reference electrode. The amorphous iridium oxide film sensor electrodes provide a potential in reference to the reference electrodes that varies according to a pH of the wound contacting the amorphous iridium oxide film sensor electrodes and the reference electrodes. A passive radio frequency identification chip is electrically connected to the first and second electrical contact pads. A tag antenna electrically connected to the passive radio frequency identification chip. The present invention also provides a system for detecting the condition of a wound by adding a radio frequency identification reader comprising a computer connected to an antenna.

Brief Description of the Drawings

Further benefits and advantages of the present invention will become more apparent from the following description of various embodiments that are given by way of example with reference to the accompanying drawings: FIGURE 1 illustrates a pH sensor in accordance with one embodiment of the present invention;

FIGURE 2 illustrates an array of pH sensors in accordance with another embodiment of the present invention;

FIGURE 3 is a photo of an array of pH sensors in accordance with another embodiment of the present invention;

FIGURE 4 is a photo of an array of pH sensors in accordance with another embodiment of the present invention;

FIGURES 5A- IF illustrate a method for fabricating a pH sensor in accordance with another embodiment of the present invention; FIGURES 6A-6B are photos of the IrO _x films treated at 300 ⁰ C (amorphous) and 55O ⁰ C

(crystalline), respectively, in accordance with another embodiment of the present invention;

FIGURES 7A-7B are photos showing the AgCl electroplating layer before and after the KCl saturation process, respectively in accordance with another embodiment of the present invention; FIGURE 8 is a flowchart of a fabrication process for the pH sensor in accordance with another embodiment of the present invention;

FIGURE 9 illustrates a measurement setup to test the pH sensor in accordance with another embodiment of the present invention;

FIGURES 10A- 1OB are graphs illustrating the measured super-Nernstian potential responses in titration from pH=l .9 to pH=12.42 (FIGURE 10A) and from pH=l 1.8 to pH=l .92 (FIGURE 10B) in accordance with another embodiment of the present invention;

FIGURES 1 IA-I IB are graphs illustration the response times in titration from pH=2 to pH=8 (FIGURE 1 IA) and from pH=8.5 to pH=2.5 (FIGURE 1 IB in accordance with another embodiment of the present invention; FIGURES 12A and 12B are graphs showing the reversibility and repeatability tests on a single electrode with acid - alkaline - acid (FIGURE 12A) and alkaline - acid - alkaline solution (FIGURE 12B) titration sequences in accordance with another embodiment of the present invention;

FIGURE 13 is a graph showing the selectivity tests with different acidic and alkaline solutions in accordance with another embodiment of the present invention;

FIGURE 14 is a graph showing the potential responses of the pH sensor array in accordance with another embodiment of the present invention; FIGURES 15A-15B are graphs showing the dynamic pH titration test results in accordance with another embodiment of the present invention;

FIGURES 16A-16B are a photo (FIGURE 16A) and a diagram (FIGURE 16B) of a setup configuration for the tube test in accordance with another embodiment of the present invention;

FIGURE 17 is a graph showing the potential responses of the flexible sensors inside a small tube in accordance with another embodiment of the present invention;

FIGURE 18 illustrates a food freshness monitoring system in accordance with another embodiment of the present invention;

FIGURE 19 is a photo of a mackerel spoilage test using IROF pH sensors in accordance with another embodiment of the present invention; FIGURE 20 is a graph depicting the test results of mackerel spoilage of FIGURE 19;

FIGURE 21 is a photo of a tilapia fillet spoilage test with dry ice bags using IROF pH sensors in accordance with another embodiment of the present invention;

FIGURES 22A-22B are graphs depicting the test results of the tilapia fillet spoilage tests of FIGURE 21 with dry ice bags (FIGURE 22A) and without dry ice bags (FIGURE 22B); FIGURE 23 is a graph showing the spoilage test results of the tilapia fillet (FIGURE 21) within a 50-hour period; and

FIGURE 24 is a diagram illustrating a wound condition monitoring system in accordance with another embodiment of the present invention.

Description of the Invention While the making and using of various embodiments of the present invention are discussed in detail below, it should be appreciated that the present invention provides many applicable inventive concepts that can be embodied in a wide variety of specific contexts. The specific embodiments discussed herein are merely illustrative of specific ways to make and use the invention and do not delimit the scope of the invention. To facilitate the understanding of this invention, a number of terms are defined below.

Terms defined herein have meanings as commonly understood by a person of ordinary skill in the areas relevant to the present invention. Terms such as "a", "an" and "the" are not intended to refer to only a singular entity, but include the general class of which a specific example may be

used for illustration. The terminology herein is used to describe specific embodiments of the invention, but their usage does not delimit the invention, except as outlined in the claims.

Now referring to FIGURE 1, a pH sensor 100 in accordance with one embodiment of the present invention is shown. The pH sensing apparatus 100 includes a flexible polymer substrate 102, an amorphous iridium oxide film sensor electrode 104 disposed on the flexible polymer substrate 102 and a reference electrode 106 disposed on the flexible polymer substrate 102 in close proximity to the amorphous iridium oxide film sensor electrode 104. In addition, a first electrical contact pad 108 disposed on the flexible polymer substrate 102 and is electrically connected to the amorphous iridium oxide sensor 104 via a conductive trace, connector or pathway 112. Similarly, a second electrical contact pad 110 is disposed on the flexible polymer substrate 102 and electrically connected to the reference electrode via a conductive trace, connector or pathway 114. As will be described in more detail below, the amorphous iridium oxide film sensor electrode 104 provides a potential in reference to the reference electrode 106 that varies according to a pH of a substance contacting the amorphous iridium oxide film sensor electrode 104 and the reference electrode 106. Note that the present invention is not limited to the specific orientation shown in FIGURE 1. Moreover, FIGURE 1 is not to scale. As a result, any suitable orientation of the components can be used, and the components can be of any suitable geometric shape. One example of a process for fabricating the pH sensor 100 will be described in more detail below. Referring now to FIGURE 2, an array 200 of pH sensors in accordance with another embodiment of the present invention is shown. As shown, the pH sensor array 200 includes four pH sensors 100a, 100b, 100c and lOOd disposed on a flexible polymer substrate 102. The array can contain any number of pH sensors 100. The four amorphous iridium oxide film sensor electrodes 104 are disposed on the flexible polymer substrate 102. A reference electrode 106 corresponding to each amorphous iridium oxide film sensor electrode 104 is disposed on the flexible polymer substrate 102 in close proximity to the corresponding amorphous iridium oxide film sensor electrode 104. A first electrical contact pad 108 corresponding to each amorphous iridium oxide film sensor electrode 104 is disposed on the flexible polymer substrate 102 and electrically connected to the corresponding amorphous iridium oxide sensor 104 via a conductive trace, connector or pathway 112. A second electrical contact pad 110 corresponding to each reference electrode 106 is disposed on the flexible polymer substrate 102 and electrically connected to the corresponding reference electrode 105 via a conductive trace, connector or pathway 114. The amorphous iridium oxide film sensor electrodes 104 provide a potential in reference to the reference electrodes 104 that varies according to a pH of a substance contacting

the amorphous iridium oxide film sensor electrodes 104 and the reference electrodes 106. Note that the present invention is not limited to the specific orientation shown in FIGURE 2. Moreover, FIGURE 2 is not to scale. As a result, any suitable orientation of the components can be used, and the components can be of any suitable geometric shape. For example FIGURES 3 and 4 are photos of two different types of pH sensor arrays 300 and 400 in accordance with additional embodiments of the present invention.

Now referring to FIGURES 5A-1F, a method 500 for fabricating a pH sensor in accordance with another embodiment of the present invention is shown. More specifically FIGURE 5 A shows the Cr and Au deposition on a Kapton polyimide substrate 102, FIGURE 5B shows the SU-8-100 deposition for the sacrificial layer, FIGURE 5C shows the IrCl ₄ sol-gel process, FIGURE 5D shows the thermal treatment, FIGURE 5E shows the Cr, Pt and Ag deposition and FIGURE 5F shows the AgCl electroplating.

The pH sensor 100 was fabricated by standard photolithography and lift-off processes. All metal layers were deposited by electron-beam evaporation. First, a layer of 7-nm thick Cr was deposited on a piece of Kapton polyimide substrate 102, followed by a 0.1 -μm thick layer of Au. Iridium oxide sensing film was formed by the sol-gel process [30] which will be discussed in more detail below. 7-nm thick Cr and 3-nm thick Pt were evaporated for adhesion. A 30-nm thick silver layer then was deposited by electron-beam evaporation. Silver chloride (AgCl) reference electrodes were formed by electroplating. IN this particular example, the working and reference electrode areas were 2x2 mm ² .

The Sol-gel process will now be described. IrO _x films were selectively deposited with sol-gel processes onto the gold electrodes. The electrodes were exposed through small windows in the SU-8 sacrificial layer, as shown in FIGURE 5B. The sol-gel coating solution was based on the recipe described in [30]. One gram of anhydrous iridium chloride (IrCl ₄ ) was dissolved in 42 ml of ethanol (C ₂ H ₅ OH). 10 ml of acetic acid (CH ₃ COOH) was added in the solution. The coating solution was stirred by a magnetic rod for one hour.

Thin film was formed by dip coating at a 2.0-cm/min withdrawing rate in the solution. After dip coating, the sample was thermally treated with a heating profile starting at 25 ⁰ C to 300 ⁰ C in a 2-hour period. The temperature stayed at 300 ⁰ C for 5 hours. To obtain amorphous iridium oxide film, the surface needs to be heated at or above 300 ⁰ C [30-32]. The furnace was then cooled down in a 10-hour period to 25 ⁰ C. FIGURES 6A-B show the morphology of the IrO _x surface at peak treatment temperatures of 300 ⁰ C (amorphous) (FIGURE 6 A and 55O ⁰ C (crystalline) (FIGURE 6B) using the ZEISS Supra 55 VP scanning electron microscope (SEM). At 300 ⁰ C, an amorphous surface was formed without cracks. As can be seen in FIGURE 6A, the

surface is uniform and smooth, even at the boundaries to the gold layer where cracks form often due to thermal treatment. The iridium oxide thin film crystallized at 550 ⁰ C [31] and the surface cracked at multiple places across the film, as shown in FIGURE 6B. For the pH sensor applications, a uniform film surface is required. After experimenting at different temperatures, the 300 ⁰ C heat treatment was shown to provide good film quality.

The electroplating process of the AgCl layer will now be described. An electrochemical anodization process was used on an anodic silver electrode with a platinum cathode electrode in 0.1 -M HCl solution. An electrical current of 0.5 mA was applied on electrodes in HCl solution for 5 seconds. During the electrolysis, a brown silver chloride layer was formed on the silver surface as shown in FIGURE 7A. The electrode surface was rinsed by DI water and then immersed in 3 -M KCl solution for 24 hours to saturate and stabilize potentials [45]. FIGURE 7B shows the electrodes after the saturation process.

Now referring to FIGURE 8, a flowchart of a fabrication process 800 for the pH sensor in accordance with another embodiment of the present invention is shown. A chromium layer and a gold layer are deposited (e.g., electron-beam evaporator, etc.) on a flexible polymer substrate, such as a Kapton polyimide flexible substrate or other suitable material, to define a sensor electrode and a first electrical contact pad in block 802. A sacrificial layer, such as SU-8 or other suitable material, is deposited on the first electrical contact pad and the flexible polymer substrate in block 804. The sacrificial layer and the sensor electrode are coated (e.g., dipcoating process, etc.) with an iridium oxide thin film in block 806. The sensor electrode is heated to form an amorphous iridium oxide sensor electrode in block 808. The sacrificial layer is removed in block 810. A chromium layer, a platinum layer and a silver layer are deposited (e.g., electron- beam evaporator, etc.) on the flexible polymer substrate to define a reference electrode and a second electrical pad in block 812, and the silver layer is electroplated in block 814. Additional steps may include applying a sacrificial layer of Sl 813 to the chromium, platinum and silver layers; followed by the removal of the sacrificial layer of S1813. Note that the heating step can be at 150 degrees Celsius for at least 1 hour followed by a second heating step of 300 degrees Celsius for another 5 hours after the sacrificial layer is removed. The second heating step is performing in an oven purged with inert gas starting at 25 degrees Celsius and increasing to 300 degrees Celsius in a period of 2 hours, and staying at 300 degrees Celsius for another 5 hours. The step of depositing the sacrificial layer may include the steps of (a) depositing the sacrificial layer using a spin cycle, (b) heating the sacrificial layer at 65 degrees Celsius for 3 minutes and then 10 minutes at 95 degrees Celsius, and (c) developing and drying the sacrificial layer.

Referring now to FIGURE 9, a measurement setup 900 to test the pH sensor is shown. A NI-DAQ 6008 USB card with a Lab VIEW program was used for analog potential recording. A commercial Hanna pH sensor was used to verify the pH values of solution. The pH sensor array was clipped by a flat gator clamp and connected to the DAQ card. The pH sensor was immersed in acid or alkaline based diluted solution with a magnetic rod stirring at the bottom of the beaker. Hydrochloric acid and acetic acid were used for acidic tests while NH3 and KOH solutions were used for alkaline tests. The Hanna pH sensor was placed in the test solution. The potential and pH values were displayed and recorded in a computer simultaneously.

Three possible mechanisms have been proposed for pH dependent redox equilibrium between two oxidation states of the iridium oxide [46] as

Ir ₂ O ₃ + 6H ⁺ + 6e ^~ <→ 2Ir + 3H ₂ O (1)

IrO ₂ + AH ⁺ + Ae ^' <→ Ir + 2H ₂ O (2)

2IrO ₂ + 2H ⁺ + 2e ^" <-> Ir ₂ O ₃ + H ₂ O (3)

RT E = E ⁰ - 2.303— pH = E ⁰ - 59 λ6pH (4)

where: E ⁰ is the standard electrode potential with a value of 926 mV;

F is the Faraday's constant with a value of 96,487 coul/equiv; and R is the gas constant with a value of 8.314 joules/deg.

RT/F is equal to 25.688 at 25 ⁰ C. The pH potential sensitivity is 59 mV/pH if space charges are formed [22,46] which is called the Nernstian response. The pH sensitivity of our sensor is based on the super-Nernstian potential response [44] as the sensitivity will be higher than 59 mV/pH.

The sensitivity of IrO _x pH sensor was validated by pH titration tests at the room temperature. DI water, HCl, and KOH were used during the titration. Three sensor electrodes in an array were used to demonstrate the linear super-Nernstian response. FIGURE 1OA shows the potential responses with eight different pH levels from 1.9 to 12.42 as KOH was dripped in the diluted HCl solution for titration. The results showed sensitivity ranging from -71.5mV/pH to - 81.7mV/pH [43]. FIGURE 1OB shows the potential responses with seven different pH levels from 11.8 to 1.92 resulting in sensitivity between -69.6mV/pH and -71.8 mV/pH as HCl was dripped in diluted KOH solution for titration. The different sensitivities may be caused by the state of oxide [49]. The sensitivity of IrOx increases when the oxidation state reduces. A higher potential coincided with a high valence oxide and vice versa [49]. During the tests, our pH electrode array on flexible substrate showed higher sensitivity, compared to the electrode formed by other methods which typically have sensitivities in the range of 55-70 mV/pH [22, 47-48].

The response time of the pH sensor was measured in two tests with one from acidic to alkaline solutions by dripping KOH into acidic solution, and one from alkaline to acidic by dripping HCl into alkaline solution. The response time of pH electrodes is defined as the time required to reach 90% of the equilibrium value [36]. FIGURE 1 IA shows the measured potential compared with the pH values measured by the Hanna pH sensor from pH=2 to pH=8 with KOH dripping. The response time was around 10 seconds. The potentials of two electrodes were shifted by 0.045V due to the potential influence from the Hanna sensor electrode as the electrode #2 was placed close to the Hanna sensor electrode. FIGURE 1 IB shows the result from pH=8.5 to pH=2.5 with HCl dripping and the response time is 7 seconds. The results of response time measurement may be affected by the porous properties of IROF. The bulk pH solution needs to equilibrate the solution in the pores of iridium oxide film [49] which may increase response time during the tests.

The reversibility and repeatability tests of IrO _x pH sensor were performed to evaluate the need for frequent recalibration that is required for many pH sensors [51]. The pH sensor was tested in the acid - alkaline - acid and alkaline - acid - alkaline sequences as shown in

FIGURES 12A and 12B, respectively, with the Hanna pH sensor as reference. In the acid - alkaline - acid test sequence, the solution was based on diluted HCl in which the pH value reading from the Hanna pH sensor is 2.8. IM OfNH ₃ was dripped in the HCl based solution changing the pH reading of the Hanna sensor to 9.8, and our sensor's potential changed from 0.28 V to -0.09 V. Then IM of HCl was dripped into the alkaline based solution. Our sensor's potential changed back to 0.3 V while the Hanna pH sensor reading was 2.4. In the alkaline - acid - alkaline sequence, our sensor measured 0.023 V with a pH = 7 by the Hanna sensor reading. IM of HCl was then dripped into the solution changing the pH reading of the Hanna sensor to 2.3, and the potential of our sensor was changed to 0.31 V. Then NH ₃ was dripped in the solution changing the pH value to 10.5, and the potential of our sensor was changed from 0.31 V to -0.041 V. This test shows that the reversibility of the IROF sensor and the results are repeatable.

Two different acidic solutions HCl and CH ₃ COOH and two different alkaline solutions KOH and NH ₃ were used for selectivity tests. Random amounts of these acidic or alkaline solutions were dripped into the beaker in which the solution was stirred by a magnetic rod. The results are shown in FIGURE 13. The potentials followed the pH values independently with the different types of solutions. The detected potential responded quickly to the added solution as it was dripped near the sensor electrode. As the added solution was stirred into the base solution, the potential slowly changed. In this test, noises of potential happened due to the disturbance of

solutions by the stirring rod. The IROF sensor responded to pH variations, independent of titration solutions, showing specificity to only pH values.

FIGURE 14 shows the potential responses of the IrO _x electrodes in a series of different pH levels. Three sensors in an array were tested simultaneously in the same titration beaker. The diluted KOH solution was titrated by IM of HCl dripping from pH=10.4 to 1.5. The pH values were recorded by the Hanna pH sensor. During the test, the IrO _x pH sensor potentials followed the pH values coordinately from -0.0 IV to 0.25V, and kept stable in each pH step. Three electrodes in the array behaved similarly with little difference. The difference in potentials may be due to the difference in locations of electrodes with respect to the titration solution HCl dripping location in the beaker. In addition, another potential drift phenomenon happened in each titration event. When acid was dripped into the beaker, the potential indicating the respective pH level jumped to a certain value, but then started to reduce and stabilize slowly until the next titration event. This potential drifting in each titration step might be introduced by the oxidized state also described by Olthuis et al [49]. In a pseudo-random titration experiment, we used two IrO _x electrodes that were fabricated in different batches. Both electrodes have been used in many titration tests and aged one month. The pH levels were varied by dripping random acidic or alkaline solutions into a beaker. FIGURE 15A shows the time-lapsed record of the measured potentials from two different electrodes. The arrows indicate the titration event. FIGURE 15B compares the pH values derived from the measured electrode potentials with the pH values measured by the

Hanna pH sensor. The changes of potentials corresponded to the pH variations of the solution instantly and repeatedly during the random titration process. The results showed potential drifts at the same pH values that were detected by the Hanna pH sensor. Assuming the Hanna pH sensor did not drift, the observed phenomenon may be caused by the following reasons: (1) since during titration acid or alkaline solutions were dripped into deionized water which had very low ion concentration, the ion source in the beaker mainly was from the titration solutions. The ion concentration varied and redistributed with time even the pH values were the same. The localized ion concentrations detected by the IROF electrodes then varied. The Hanna sensor has a large sensing area so it may be sensitive to local ion concentration variation. (2) Mentioned previously, the drifting problem may be caused by the different oxidation states [49] on the film. Besides the potential drifts, the two sensors from two different fabrication batches produced slightly different potential levels at the same titration section. The phenomenon may be caused by the chloride ions that were not fully removed from the coating surface during the annealing process [50] and different oxidation stages since they were fabricated at different times. Despite

these factors, our iridium oxide sensors clearly indicated the random pH variations of the solution.

A sensor in accordance with the present invention can be used for the reflux detection in human esophagus [52] for which the flexible sensor needs to fit into a small confined space where it is difficult to use convention glass electrode pH sensors. As shown in FIGURE 16A, our IrO _x pH sensor array was bent and inserted into a long tube with a diameter of 2 cm. The tube was filled with pH=7 DI water first, then 0.1-M KOH and 1-M HCl were dripped pseudo- randomly into the tube. A magnetic stirrer was used at the bottom of the tube as shown in FIGURE 16B to mix the solution. The sensor electrode array was arranged vertically. The array has three electrodes with a spacing of 3 mm between them giving a spatial resolution of 3 mm for localized pH sensing. Due to the small tube diameter, the commercial Hanna pH sensor was not able to be placed inside the tube to measure the pH values. FIGURE 17 shows the potential changes with pseudo-random drips of acidic or alkaline solutions. The potential variations in each electrode responded to the titration quickly and coordinately. With the electrode #3 at the top and the electrode #1 at the bottom, the potential peak values of the electrode #3 were always higher than those from the electrode #1. This again was due to the spatial distributions of the ion concentrations. This phenomenon was more obvious in the beginning of the experiment when HCl was first added into the deionized water. As more titration solutions were added, more ions existed in the tube and so the differences of potentials among three electrodes became less. The sensor electrodes locally detected the potentials from the pH dependent redox equilibrium. With calibration of the initial conditions on the electrodes in an array, the sensor array can provide time-lapsed spatial information of pH values.

The present invention, therefore, provides an iridium oxide film based pH sensor on a flexible polyimide substrate that provides the advantages of lower costs, simpler processes and improved device flexibility. Some additional uses of the iridium oxide film based pH sensor in accordance with the present invention as a passive wireless (RFID) detector will now be described. Note that other uses that are not specifically described herein, such as active wireless RFID detectors, are within the scope of the present invention.

The present invention can be used to detect spoilage of food (e.g., meat, fish, etc.) The pH sensors on flexible substrates can be used in monitoring pH values in food processes in food industry, chemical processes in pharmacy and material supplier industry and biochemical reaction monitoring in medical applications. In applications targeting for supermarket and food supply chain industries, the freshness of meat and fish is monitored using the flexible iridium oxide pH sensor. The packages will require miniature flexible sensor that is biocompatible. The

sensor has to be miniature and flexible so it can be embedded with a RFID chip inside a plastic label. The flexibility of sensor will allow the sensor to conform to the surface of the meats or fishes packaged. The sensor electrode has to be biocompatible and safe since it will be touching the food until it is consumed. The sensor device architecture should also allow integration with existing RFID communication methods.

For example, the present invention provides a packaging system for meat and fish in retailer supermarkets or supply chains. The system 1800 shown in FIGURE 18 includes packages consists of RFID sensor-embedded plastic wrappers and RFID readers. A reader antenna 1802 connected to a computer 1804 sends out RFID inquiring radio-frequency signals 1806 to the storage area 1808. Each package 1810 contains meat or fish 1812 wrapped by a plastic wrapper 1814. Inside the wrapper 1814, a label 1816 facing outside and showing information (barcode, nutrition information, price, expiration date and etc) about the package 1810 has an embedded sensor 100 or sensor array 10Ox, a RFID chip 1818 and a tag antenna 1820 inside. The sensor 10Ox touching the meat or fish 1812 can sense the pH value. When the inquiring RFID signal 1806 sent by the reader ( 1802 + 1804) is received by the tag antenna 1820 and the inquiring ID matches with the ID in the package chip 1818, the chip 1818 harvests the received radio-frequency signal powers 1806 and uses the powers to drive the sensor 10Ox to detect pH value of the meat/fish 1812. The RFID chip 1818 then sends out the RFID and sensor information (collectively 1822) back to the reader (1802 +1804). Note that a visual indicator could be added to the exterior of the package 1810 to indicate the pH of the food.

Using this sensor-embedded RFID method, it does not require workers to check individual packages manually for freshness of meats or fishes which is time and effort consuming. The freshness information can be obtained remotely by a computer and monitored continuously. Each package RFID also contains packaging and expiration dates so the computer can flag alerts when the packages are about to expire.

The relationship between the meat/fish freshness and pH changes has been investigated. After livestock is killed, the oxygen stops to deliver into muscle which induces several different biochemical reaction changes. These changes contribute various meat flavors and stages of spoilage. Generally speaking, meat property variations follow three steps: Step 1 - Rigor mortis (pH reduces)

Because of the lack of oxygen in the dead muscle, the glycogen will be decomposed and become the lactic acid. On the other hand, the Adenosine Tri Phosphate (ATP) is hydrolyzed to be phosphoric acid too. The pH level of the muscle group will reduce, and muscle becomes hard. We call the phenomenon "Rigor Mortis".

Step 2 - Autolysis (pH slightly increases)

After the rigor mortis, the muscle will be dissolved to become the smaller molecule by enzyme. The muscle will become much softer as called off-rigor. The protein in the dead muscle also dissolves to be the amino acid which includes different types of structure ex. Amine. On this moment, the pH level of muscle group will increase.

Step 3 - Spoilage (pH increase)

With amino acid producing, some microbes start to grow and absorb the amino acid and proteins. There are different chemicals such as Indol, Scatol, ammonia, and sulfide created after the absorbing processes created by bacteria. The ammonia-based chemicals increase pH level of the meat/fish and bad odors.

As described above, the pH variations of food is related to spoilage. The transitions of acid-slight alkaline-alkaline could be used to identify the stages of meat spoilage. The IROF (iridium oxide film) based pH sensor in accordance with the present invention is use as the indicator to recognize the time line in the spoilage process. Testing of the sensor 10Ox will now be described.

Frozen whole -body mackerels were used as the test samples in the first test. Three individual iridium oxide sensors were placed in three different parts, which were belly, gill and muscle as shown in FIGURE 19. The test was conducted at the room temperature of 25°C for 90 hours. The potentials from the sensor electrodes were recorded continuously by a computer. FIGURE 20 shows the time-lapsed results. The sensor showed clearly the sensor potential changes in the transition of alkaline-acid-alkaline on fish meat (muscle) section, while the gill and belly sections indicated acid to alkaline changes. The pH value transitions do not follow exactly the spoilage mentioned earlier, however, the pH changes do indicate the freshness changes. The fish started to emit odors after 30 hours indicating the fish became spoiled, as the measured pH value started to change significantly.

Next a tilapia fillet test was conducted that focused on comparison of the fish meat properties under different temperatures. One fillet was wrapped by the dry ice bags, as shown in FIGURE 21, for 24 hours while the other fillet was tested at the room temperature of 25 ⁰ C. The one at the room temperature should go spoiled quicker. The IROF pH sensors were inserted between flesh in the both samples. FIGURE 22A shows the results after 24 hours. The one wrapped by the dry ice bags has no dramatic potential changes, which means the pH value kept constant around the same level. This may indicate that there were no microbes growing and no obvious odor was detected. However, the sensor inside the fillet without the dry ice bags wrapped has dramatic potential variations within the 24-hour period. The alkaline-acid-alkaline

transition pattern was showed in FIGURE 22B. The pH level changed probably because of the chemical reaction and microbes growing as mentioned before. An obvious odor was detected in this fillet.

FIGURE 23 shows the spoilage test results of the tilapia fillet within a 50-hour period. There were clearly three spoilage steps. The step 1 shows the lactic and phosphoric acid generating from glycogen and ATP. The sensor detected an acid value with a potential increase in the first 10 hours. At the step 2, the potential started to drop after 12 hours indicating a change to alkaline. This is because the protein was decomposed to amino acid by enzyme. The pH level slightly increased and the potential dropped due to the amine from the amino acid. However, there were still some compositions such as CO ₂ , lactic acid and etc left in the muscle. The pH level may drop due to neutralization of the alkaline elements by residual acidic elements. In the step 3, a clear spoilage happened after 26 hours. The pH level increased and potential dropped because of the ammonia (NH ₄ ). At the same time, the microbes started to grow and produced the compositions such as Indol, Scatol, and amino nitride etc, which generated a distinct odor. The foregoing tests demonstrate that the flexible iridium oxide pH sensor detected the pH level changes due to the fish spoilage processes. The changes of potential detected by our sensor matched with the pH level variations corresponding to the spoilage phenomena reported in literatures.

Now referring back to FIGURE 4, a multi-sensor array 400 is used to accurately monitor various parts of the meats/fishes in a package. In the test version, the multi-sensor array 500 is a 4x4 array with sixteen iridium oxide pH sensors on a flexible Kapton substrate. The size of the whole array 400 is around 3x3 cm ² . This sensor can detect the pH level distributions simultaneously across the same area. Each sensor is connected an individual RFID so each sensor information can be individually recorded. The Kapton film is deformable so all 16 sensors can touch their respective areas on the meat/fish firmly after wrapping and packaging.

Referring now to FIGURE 24, a diagram illustrating a wound condition monitoring system 2400 in accordance with another embodiment of the present invention is shown. Wound healing is a sophisticated immune process which is represented by intercalating degradation, tissue re-assembly, and epidermal layer [53]. It is important to monitor the wound condition while the patient wears a bandage for two reasons: (1) the bandage should be changed according to the wound conditions, and (2) the different therapy agents need to be applied with respect to the wound conditions during various stages in wound healing.

For serious wound conditions, the bandage changes are done by doctors or nurses. In a hospital or trauma center, frequent changes of bandage add significant manual labors and

therefore costs. Currently, the changes of bandages are done at fixed time schedules. This is not cost effective since sometimes the bandages may not need to be changed. Unnecessary changes of bandages may cause further damage to the wounds. It is also not result effective since some of the bandages need more frequent changes at certain stages of therapy, while others should not be changed in order to avoid tissue damages. However, the caretakers may not know when is the best time to change the bandages since most of the bandages are not transparent. The bandages need to be removed in order to examine the conditions of the wounds. With the fast growing of healthcare costs, frequent visits by the doctors or nurses to the patients' bedsides may not be preferable by the hospitals. One of the significant applications is an example of wound care in a disaster site.

Problems that start in the traumatic disaster complicate the entire wound care and recovery process. Enormous energy released by the injuring weapon or causes results in massive releases of signaling agents from the blasted tissues that are interpreted by the body as messages to "over-heal". The result is gross inflammation, unregulated and rapid growth of tissues in the injury site, and massive agglomeration of scar tissue. Such over-healing is detrimental to future recovery efforts as it tangles the wound into a random configuration and hides the structure of the original injury, both of which greatly complicate surgical reconstruction. Excessive bone deposits (heterotopic bone formation) and unregulated nerve regeneration (causing neuromas) will negatively impact numerous phases of future healing. The pain signals related to these growths result in long-term debilitation and additional nerve damage. Excessive scarring contracts tissues with incredible forces, grotesquely distorting the appearance of the tissues, affecting circulation and causing numerous other problems. Furthermore, Injuries tend to embed microscopic contaminants into the body of the wound, which result in high rates of infection. Active wound monitoring and infection management are crucial during this stage to ameliorate the likelihood and severity of infections.

In the recovery period, regeneration of massive hard and soft tissue deficit is the goal. An adaptive wound monitoring and management with tissue engineering will require a continuous and convenient way for wound condition monitoring to coordinate comprehensive reconstructive surgery. For normal wound conditions, patients who wear bandages also need to know the wound conditions before replacement or seeking for further medical cares. This can be categorized into two general applications. For therapy purposes, wound conditions are monitoring to reduce scar forming and promote stable tissue regrowth. For protection purposes, the wounds are monitored to prevent infection.

Current solutions rely mainly on passive bandages for wound management without a monitoring mechanism. There is a strong need for a continuous, systematic yet flexible and reconfϊgurable wound monitoring that is lightweight, easy to implement and that provides ability to track patient's conditions. pH value is an important indication to determine wound conditions with respect to its bacterial level. The pH distribution in the large wound area is useful information during the recovering and therapy procedures. A pH sensor array on flexible substrates in accordance with the present invention can be used to monitor pH level changes across an area of wound site. The metal oxide pH sensors allow continuous and long-term monitoring of pH, compared to the short lifetime disadvantage in enzyme-based or electrochemical sensing. The sensor is in an array configuration and on a flexible substrate allowing the sensor array to deform onto body parts to monitor multiple points in an area. The invented pH sensor produces a linear relationship between pH and potentials, which can be used in a batteryless wireless telemetry system. By detecting the responding shifted frequency of the modulated signals, the pH changes on the tissue can be monitored remotely.

As shown in FIGURE 24, the flexible substrate conforms to the surface of wound. The sensor array 2406 contains multiple sensors 100 arranged in a particular spatial resolution. Each sensor 100 in the array 2406 detects the pH value in its respective spot. A RFID reader 1802+1804 transmits RF signal 1806 illuminating the wound area. The circuitry in the bandage 2402 harvests the radio-frequency energy 1806 to operate the sensor electrodes and a voltage- controlled oscillator. The oscillation frequency is controlled by the potential generated from the electrode. The modulated signal then is carried by the same resonant frequency carrier and retransmitted back 1822 to the reader 1802+1804. The reader 1802+1804 receives the responding signals 1822 and converts them to the baseband. The frequency shifts in the baseband signals indicate the pH values.

The reader antenna 1802 connected to a computer 1804 (or PDA and other wearable electronic devices on the patient's belt) sends out RFID inquiring signals 1806 to the patient. In the bandage 2402, it consists of an iridium oxide pH sensor array 2406 fabricated on a flexible substrate, a RFID chip 1818 and a tag antenna 1820. The sensor 100 touching the wound area senses the pH level and produces responding potentials. When the inquiring RFID signal 1806 sent by the reader 1802+1804 and received by the tag antenna 1820 has the inquiring ID matched with the ID in the bandage chip 1818, the chip 1818 harvests the received radio- frequency signal powers 1806 and uses the powers to operate the sensor and circuitry. The RFID chip 1818 then sends out the RFID and sensor data back to the reader 1802+1804 with the same

carrier. The reader antenna 1802 connected to the computer 1804 receives the signals 1822, verifies the RFID 1818 and logs the sensor data into the computer 1804. Note that a visual indicator could be added to the exterior of the bandage 2402 to indicate the pH of the wound.

The normal pH level of human skin is between pH 4-7 [53] which depends on age, sex, and race of the person. The different location of skin also has different pH value. Harrison and Walker mentioned that the pH of human's dermis was 7.54±0.09 tested by glass pH electrode [54]. The physiological pH value is affected by amino acids, fatty acids, and others produced by the skin appendages [53].

In the beginning of an infection, the pH level of tissue may decrease because the bacteria share the nutrients and oxygen with the tissue cells. The phenomenon is called ischemic condition which may result the metabolism of tissue cells becoming anaerobic and therefore acidic [55].

In a chronic wound, there are different bacteria such as staphylococcus aureus and enzymes such as as staphylococci may contaminate the wound area and delay the healing process. Some results in in- vitro experiment showed those microbes perform the overgrowth and active activity in higher pH level milieu [53]. In another study, the high-level pH environment slowed down the cell migration and DNA synthesis during the healing process [56].

In the literature [54], the animal and clinical studies have been done and shown an approximately linear response between the number of bacteria and the pH level. With an increase in bacteria counts, the pH level decreases. In the publication [53], the wound pH values were measured by an invasive glass electrode showing that the pH value dropped from 7.4 to 6.6 in the wound healing process. The wound condition was shown improved with the pH value decreased.

Although the present invention and its advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims. Moreover, the scope of the present application is not intended to be limited to the particular embodiments of the process, machine, manufacture, composition of matter, means, methods and steps described in the specification, but only by the claims.

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