In Vivo Verification of Implantable Antennas Using Rats as Model Animals

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334 IEEE ANTENNAS AND WIRELESS PROPAGATION LETTERS, VOL. 9, 2010 In Vivo Verification of Implantable Antennas Using Rats as Model Animals Tutku Karacolak, Robert Cooper, James Butler, Stephen Fisher, and Erdem Topsakal, Senior Member, IEEE Abstract—The main objective of this study is to test in vivo a small-size dual-band implantable antenna operating in Medical Implant Communications Service (MICS) (402–405 MHz) and In- dustrial, Scientific, and Medical (ISM) (2.4–2.48 GHz) bands and to investigate the effects of live tissue on the antenna performance. To do so, we have designed and fabricated three identical antennas that were surgically implanted into rats at Mississippi State Uni- versity’s (MSU) College of Veterinary Medicine. X-ray images are also taken to ensure the proper placement of the antenna within the body. Results regarding return loss measurements and the perfor- mance change of the antenna are presented. We have also investi- gated possible candidate materials that can be used for encasing of the antenna for biocompatibility. Index Terms—Implantable antenna, in vivo, Industrial, Scien- tific, and Medical (ISM) band, Medical Implant Communications Service (MICS) band. I. INTRODUCTION I MPLANTABLE wireless telemetry systems have been studied recently for wireless monitoring of physiological parameters such as glucose, blood pressure, temperature, etc. [1]–[4]. Because the implantable antennas provide communi- cation between the implant and the external environment, their efficient design is vital for overall system reliability. Thus far, implantable antenna designs have been limited to in silico and in vitro studies [5]–[9]. Because the electrical properties of the live tissues are dependent to changes in temperature, age, and tissue chemistry, in vitro verification of these antennas does not guarantee their proper functioning when implanted in the body. Therefore, in vivo testing becomes vital to investigate the effects of the live tissue on the antenna performance. This is also a necessary step to provide useful feedback information to the designer for further antenna modifications if needed. In a recent study, an implantable dual-band antenna operating in MICS and ISM bands was designed using electrical prop- erties of rat skin [10]. The resulting antenna had dimensions of 23 23 2.5 mm , and Rogers RO3210 ( , tan ) was used for the sub- and superstrate material. A serpentine configuration was also considered for optimizing the Manuscript received March 22, 2010; accepted April 08, 2010. Date of pub- lication April 22, 2010; date of current version May 06, 2010. T. Karacolak and E. Topsakal are with the Department of Electrical and Com- puter Engineering, Mississippi State University, Mississippi State, MS 39762 USA (e-mail: [email protected]; [email protected]). R. Cooper, J. Butler, and S. Fisher are with the College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762 USA (e-mail: [email protected]). Color versions of one or more of the figures in this letter are available online at http://ieeexplore.ieee.org. Digital Object Identifier 10.1109/LAWP.2010.2048693 Fig. 1. (a) In vitro testing of implantable antenna. (b) Implantable antenna. Fig. 2. Return loss of the antenna designed in [10]. antenna surface area. The fabricated antenna was in vitro tested using both rat skin-mimicking materials and real skin samples [see Fig. 1(a) and (b)]. The return loss of the antenna is seen in Fig. 2. The goal of this study is to investigate how this antenna will function within the live tissue. In order to perform the in vivo measurements, we collabo- rated with Mississippi State University’s College of Veterinary Medicine (MSU-CVM). We purchased three rats in order to produce statistically valid data. The antennas are implanted in rats at the MSU-CVM facilities. Following the surgery, the re- turn loss measurements are performed using an Agilent E8362B PNA network analyzer. X-ray images are also taken to observe the proper placement of the implant in the body. Results re- garding the return loss change of the antenna are presented in detail. II. SURGICAL PROCEDURE We first sterilized the antennas by leaving them in a sterile so- lution over night. During the surgeries, rats are first anesthetized with an intraperitoneal injection of a mixture of ketamine/xy- lazine. The site for implantation is on the dorsal midline just 1536-1225/$26.00 © 2010 IEEE

Transcript of In Vivo Verification of Implantable Antennas Using Rats as Model Animals

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334 IEEE ANTENNAS AND WIRELESS PROPAGATION LETTERS, VOL. 9, 2010

In Vivo Verification of Implantable AntennasUsing Rats as Model Animals

Tutku Karacolak, Robert Cooper, James Butler, Stephen Fisher, and Erdem Topsakal, Senior Member, IEEE

Abstract—The main objective of this study is to test in vivo asmall-size dual-band implantable antenna operating in MedicalImplant Communications Service (MICS) (402–405 MHz) and In-dustrial, Scientific, and Medical (ISM) (2.4–2.48 GHz) bands andto investigate the effects of live tissue on the antenna performance.To do so, we have designed and fabricated three identical antennasthat were surgically implanted into rats at Mississippi State Uni-versity’s (MSU) College of Veterinary Medicine. X-ray images arealso taken to ensure the proper placement of the antenna within thebody. Results regarding return loss measurements and the perfor-mance change of the antenna are presented. We have also investi-gated possible candidate materials that can be used for encasing ofthe antenna for biocompatibility.

Index Terms—Implantable antenna, in vivo, Industrial, Scien-tific, and Medical (ISM) band, Medical Implant CommunicationsService (MICS) band.

I. INTRODUCTION

I MPLANTABLE wireless telemetry systems have beenstudied recently for wireless monitoring of physiological

parameters such as glucose, blood pressure, temperature, etc.[1]–[4]. Because the implantable antennas provide communi-cation between the implant and the external environment, theirefficient design is vital for overall system reliability. Thus far,implantable antenna designs have been limited to in silico andin vitro studies [5]–[9]. Because the electrical properties of thelive tissues are dependent to changes in temperature, age, andtissue chemistry, in vitro verification of these antennas doesnot guarantee their proper functioning when implanted in thebody. Therefore, in vivo testing becomes vital to investigate theeffects of the live tissue on the antenna performance. This isalso a necessary step to provide useful feedback information tothe designer for further antenna modifications if needed.

In a recent study, an implantable dual-band antenna operatingin MICS and ISM bands was designed using electrical prop-erties of rat skin [10]. The resulting antenna had dimensionsof 23 23 2.5 mm , and Rogers RO3210 ( , tan

) was used for the sub- and superstrate material. Aserpentine configuration was also considered for optimizing the

Manuscript received March 22, 2010; accepted April 08, 2010. Date of pub-lication April 22, 2010; date of current version May 06, 2010.

T. Karacolak and E. Topsakal are with the Department of Electrical and Com-puter Engineering, Mississippi State University, Mississippi State, MS 39762USA (e-mail: [email protected]; [email protected]).

R. Cooper, J. Butler, and S. Fisher are with the College of VeterinaryMedicine, Mississippi State University, Mississippi State, MS 39762 USA(e-mail: [email protected]).

Color versions of one or more of the figures in this letter are available onlineat http://ieeexplore.ieee.org.

Digital Object Identifier 10.1109/LAWP.2010.2048693

Fig. 1. (a) In vitro testing of implantable antenna. (b) Implantable antenna.

Fig. 2. Return loss of the antenna designed in [10].

antenna surface area. The fabricated antenna was in vitro testedusing both rat skin-mimicking materials and real skin samples[see Fig. 1(a) and (b)]. The return loss of the antenna is seen inFig. 2. The goal of this study is to investigate how this antennawill function within the live tissue.

In order to perform the in vivo measurements, we collabo-rated with Mississippi State University’s College of VeterinaryMedicine (MSU-CVM). We purchased three rats in order toproduce statistically valid data. The antennas are implanted inrats at the MSU-CVM facilities. Following the surgery, the re-turn loss measurements are performed using an Agilent E8362BPNA network analyzer. X-ray images are also taken to observethe proper placement of the implant in the body. Results re-garding the return loss change of the antenna are presented indetail.

II. SURGICAL PROCEDURE

We first sterilized the antennas by leaving them in a sterile so-lution over night. During the surgeries, rats are first anesthetizedwith an intraperitoneal injection of a mixture of ketamine/xy-lazine. The site for implantation is on the dorsal midline just

1536-1225/$26.00 © 2010 IEEE

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KARACOLAK et al.: IN VIVO VERIFICATION OF IMPLANTABLE ANTENNAS USING RATS AS MODEL ANIMALS 335

Fig. 3. Surgical implantation of the antennas into the rats. (a) Incision madethrough the skin. (b) Placement of the implant. (c) Closing the wound. (d) Im-planted antenna.

Fig. 4. X-ray images of the implantable antenna in rat 1.

caudal to the junction of the cervical and thoracic spine. Thesite and surrounding region is then clipped with a #40 clipperhead, and a sterile prep is performed with betadine orchlorhexi-dene. The region is draped, and a 3-cm incision is made throughthe skin [Fig. 3(a)]. A small pocket is made in the subcutaneoustissues large enough to accommodate the implant [Fig. 3(b)]. A3-mm stab wound is made to allow the coaxial cable attachedto the antenna to exit the skin. The implant is placed in thewound, and the wound is finally closed with #4-0 nylon sutures[Fig. 3(c)]. Return loss measurements are performed immedi-ately after the surgery, and euthanasia is applied to rats as soonas the measurements are completed. The time lapse from thestart of the surgery to euthanasia was 13–15 min for each rat.X-ray images of the implantable antenna in one of the rats arealso shown in Fig. 4.

The implanted antenna and the in vivo measurement setupare shown in Fig. 5. The return loss measurements are per-formed using an Agilent E8362B PNA network analyzer. Fig. 6shows the comparison between the average return loss versusfrequency. As seen from the measurements, although the an-tenna is operating well within the anticipated frequency bands(MICS and ISM bands), there is also a substantial discrepancybetween the measured and simulated return loss. These results

Fig. 5. The implanted antenna and in vivo measurement setup.

Fig. 6. The comparison between the average of the return loss measurementsand the simulation of the antenna.

prove that there are many factors affecting the antenna perfor-mance in vivo. Though we have not thoroughly investigated, weanticipate that some contributing factors can be listed as follows.

Air gap between the antenna and the skin. In order to placethe implant between the skin and fat layers, the surgeons createda pocket large enough to accommodate the implant. Althoughwe tried to press the skin onto the antenna before measurements,it is very likely that we failed to eliminate all the air gaps be-tween the antenna surface and skin. Even small gaps will havean impact on the performance.

Interstitial fluid between the antenna and skin. Interstitialfluid is a white substance that provides nutrients to the cells. Wedid not incorporate the interstitial fluid in our simulations.

The internal body temperature. Temperature is another pa-rameter that affects the electrical properties of the tissue [11],[12]. Our simulations and in vitro tests are conducted at the roomtemperature, and the electrical properties of the skin at the roomtemperature are slightly different than that of the in vivo tissueproperties.

Other factors. One other major factor that might likely to con-tribute in the results is the age of the animal. Based on the pre-vious studies on rats, it has been shown that adult rats have sig-nificantly lower dielectric properties compared to younger ratsdue to the decreased water concentration within the tissue [13].The animals we used were the same breed, age, and sex. How-ever, because of the time lapsed between the purchase of theanimals and surgeries, we anticipate that aging of the animalsalso contributed in the discrepancy of the simulated and mea-sured return loss results.

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336 IEEE ANTENNAS AND WIRELESS PROPAGATION LETTERS, VOL. 9, 2010

Fig. 7. Far-field patterns for (a) 402 MHz and (b) 2.4 GHz.

Fig. 8. Gain patterns for 402 MHz and 2.4 GHz.

We are currently working on updating our simulation modelin order to investigate the effects of these aforementioned pa-rameters. Doing so, we aim to better understand the reasonsbehind the discrepancy between the simulation and measure-ments throughout the frequency band of operation as well as thewidening of the MICS band for the measured antenna as seen inFig. 6.

In order to show the proper radiation characteristics of theantenna, in Figs. 7 and 8, we show simulation results regardingthe antenna radiation pattern and gain, respectively.

III. BOTTLENECKS REGARDING LONG-TERM TESTING

OF THE IMPLANT

As mentioned in the previous sections, implantable an-tennas need to be long lasting, and they should not harm thesurrounding tissue. Therefore, long-term in vivo studies areimportant to ensure the proper functioning of the implant andto investigate the possible reactions of the tissue to the antenna.Because animal studies are tightly regulated in the U.S. and aresubject to approval by a committee (Institutional Animal Careand Use Committee, IACUC), during the initial phase of thisstudy, we were not able to obtain necessary approval to performlong-term studies without the proper encasing of the antennas ina medical-grade biocompatible material. Encasing the implantwith a biocompatible material is also necessary to reduce the

Fig. 9. (a) Silicone. (b) Antenna encased in the silicone.

Fig. 10. (a) Relative permittivity and (b) conductivity of the silicone in thefrequency band of 300 MHz–3 GHz.

effects of the capsular contracture. Capsular contracture is thecapsule-shaped scar tissue that forms as an immune responsearound foreign materials like implants.

Recently, we have investigated potential medical-grade ma-terials for antenna encasing. In the next section, we discuss apotential candidate that can be used as an encasing agent for theproposed antennas.

IV. BIOCOMPATIBLE ENCASING AND ONGOING STUDIES

Of the several materials we have investigated, we have con-cluded that Silastic MDX4-4210 Biomedical-Grade Base Elas-tomer is a good candidate for our application. It is very easy toprepare, and it has the desired viscosity for antenna encasing.The material comes with a curing agent that needs to be mixedwith a 10:1 ratio. In order to reduce the air bubbles in the mix-ture, we used a vacuum mixer. After the mixture had success-fully been developed, we poured the mixture onto the antenna.We cured the antenna for 2 h at 55 C. The resulting silicone ma-terial and the antenna encased in the silicone are shown in Fig. 9.As seen from Fig. 9(a), the material is very elastic. Because theelectrical properties of the silicone will alter the antenna reso-nant frequency, we performed dielectric property measurementsfor the developed material. Fig. 10 shows the relative dielec-tric constant and conductivity between 300 MHz and 3 GHz.The relative permittivity seems to be constantover the entire band, while the conductivity is almost zero. Toshow the effect of the encasing on the antenna performance, wehave also performed return loss simulations. The simulated re-turn loss of the new antenna is compared to the one without sili-cone encasing, and the results are shown in Fig. 11. As expected,the silicone significantly affects the antenna performance, and

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KARACOLAK et al.: IN VIVO VERIFICATION OF IMPLANTABLE ANTENNAS USING RATS AS MODEL ANIMALS 337

Fig. 11. The comparison between the return loss of the encased antenna andthe original antenna from [10].

the antenna needs to be reoptimized to allow MICS/ISM bandoperation.

We are currently working on modifying the antenna topologyaccording to the electrical properties of the silicone. Oncethe antenna is modified, three sets of measurements will beperformed for the long-term study: 1) immediately after thesurgery; 2) two weeks; and 3) one month post-surgery. We arealso planning on using X-ray and CT images to observe thedevelopment of the scar tissue surrounding the implant. After amonth of observation, we will extract samples from the tissuesurrounding the antenna and perform histogram to observe thecellular changes, if any, due to implant.

V. CONCLUSION

In this study, a dual-band implantable antenna for wirelesstelemetry systems is tested in vivo using rats, and return lossmeasurements are performed. Although the antenna seems tobe functioning the desired MICS/ISM band, we observed dis-crepancies between the simulated and measured results. We arecurrently working on modifying our simulations to investigatethe discrepancy. In addition, we are planning to perform long-

term studies using silicone-based biocompatible materials as de-scribed in the previous sections.

REFERENCES

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