Team 8

Members : Cyril Manjooran, Rasean Hyligar & Ritu Shah

Facilitator : Dr. Yang Dai

Problem 3 : A Device to Determine the Ingestion of Medication

SmartSense: An Automated Medication Diagnostic Tool

May 4th, 2018

Introduction

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The rapid shift in the development of communication technologies, and implantable sensors meant for biological systems, represents a dynamic paradigm in the world of point-of care and digital medicine. The advent of medication nonadherence presents a complication for the provision of new healthcare metrics. The nonadherence with medications associated with simpler diseases like diabetes and hypertension increase the expenditures to approximately $108.5 billion in a 2010 study [1]. An initial step of mitigating the financial and associated losses is the inclusion of a diagnostic tool, like smart medical dispensers in the mass market. The next step in adherence conformation is the ability to determine whether an ingestible was taken. Implementation of the SmartSense system with the use of radio-frequency identification (RFID) pill tagging, monitoring using a digital sensor, and interfacing with the SmartMed system, will reduce the gap in medical adherence.Background of Methodologies A. Tag Design

A system based around a sensor which is designed to be tagged onto patient medication follows a method of microfabricated chip integration. The integrated circuit which the chip is, uses a fabrication technique with dimensions of 1mm x 1mm x 0.3 mm [2]. With the deposition of thin films as an active layer, these act as a driving mechanism for the tag [Fig 4]. The two active layers are magnesium (Mg) and cuprous chloride (CuCl) which would envelop a silicon layer. When in contact with gastric fluid, the layers form a electrochemical battery which powers the tag; the reaction is given by, Mg(s) + 2CuCl(s) → 2Cu(s) + 2Cl−+Mg2+ (aq) [2]. The reactions continue as long as electrode materials are present, and thus far in-vivo values of battery lifetime approximate to 4 minutes [2]. An insulating layer allows for signal amplification and propagation to relay information to RFID capsule. B. RFID Bio-capsule

The RFID capsule (SmartSense) is the major monitoring component which interfaces with the tag, SmartMed system, and wearable [Fig 1 - 4]. The novelty of this system is the ability to keep it suspended in the gastrointestinal tract (GI) for an extended period of time. The material the capsule is composed is a shell made of polyethylene (gelatin). A planar dipole configuration is what constitutes the resonance of the capsule antenna, this can resonate between 0.7 and 1.2 GHz but operates around 900 Mhz [3]. With an inductive feed loop coupled with the dipole, as the feed loop length increases with the coupling reactance of the capsule increases with a optimal length of 3.9 mm [3]. The increased reactance can be expressed to show location more easily, which is when being suspended is imperative. A photolithographic technique can be used to mass fabricate the capsule.C. Foldable RFID Suspension

To be able to relay information of the RFID capsule, it must rest in a stationary position for an extended time period. Implementing a biocompatible material which is able to fold into a compact shape and unfurl is essential. Once ingested the foldable encapsulation uses electromagnetic actuation by a rotating magnetic field. The magnetic flux from the neodymium magnet generates a driving torque which is expressed by, τ B = mB sin(ψ − φ) where ψ∧φare vertical plane angles with respect to the surface [4]. To anchor itself, the suspension once opened keeps stationary while oscillating at angles, (Ψ, Ψ/2, −Ψ/2 and −Ψ; Ψ = 1.1 rad is the angle from the horizontal plane) [4]. This is done keeping maximum dimensions of 34.3mm x 7.8mm x 16.7mm representing length, height and width respectively.

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Device DesignA SmartMed dispenser, wearable watch, a pill tag, and SmartSense ingestible pilule

device make up the four part system of the design [Fig 1 - 4]. Each medicine is tagged with a chip, by SmartMed dispensing system, ingested by the patient. The SmartMed dispenser, modified from problem 2, tags each pill using an arm that presses a tag, with dimensions of 1mm x 1mm x 0.3 mm on with noninvasive edible adhesives (ingestible sensor)[Fig 1, 4, 5]. The pill tag is filled in to the SmartMed dispenser along with other medicines, like in problem 2. The medicine is taken according to the prescription. SmartSense, to go along with the medicine is taken biweekly, coated with gelatin, its dimensions being 0.64mm x 0.45mm x 0.9mm [Fig 2]. SmartSense is guided into the stomach using a magnet. Gastric fluids in the stomach activate SmartSense and provides power supply inducing an electrode reaction, while dissolving the gelatin coat [2]. SmartSense is suspended in the stomach with the support of anchors that open up, like origami, to support the device and keep it for the biweekly period. Once the biweekly cycle is over SmartSense is programmed to fold back into a pill and leave the digestive tract. SmartSense acts as a messenger that transmits signals between the medicine, the SmartWatch, and SmartMed; since it contains RFID receiving and transmitting sensors [3]. This RFID sensor is responsible for receiving signals from each tagged medicine, giving us the ability to count the number of medicine taken and further relay the information to the SmartWatch and SmartMed application. Calculations

Bluetooth operates on the 2.4 GHz signal and can operate anywhere from 15 to 80 meters [5]. They operate on a frequency hopping spread spectrum. RFID not only works on the same frequency as bluetooth but because of the nature of RFID, is more secure and scans quicker than bluetooth because RFID works off of reading data from a device already written onto via electromagnetic radio wave reception [5]. In dealing with syncing with the database that SmartMed already interacts with, because the synchronization depends on Wi-Fi speed, this will vary from user to user. In regards to the time it will take, taking into account that the time it takes for liquid to reach the stomach is approximately 2 seconds, once the pill interacts with the gastric fluids, the transmission to the watch is virtually instant. After the watch has received the signal, it then transmits the signal to the SmartMed device which, depending on Wifi speed can transfer the data in anywhere from 1 to 3 seconds [5]. This data will then synchronize with the cloud and the pharmacy database which will take up to a minute. So overall, the process of ingestion to data synchronization is around one minute. When it comes to cost and implementation, the RFID tags will be placed inside of SmartMed and a pressing arm will apply force to attach the tag onto the pill before it is delivered to the user for consumption. Cost wise, each RFID tag will be within the range of half dollar so cost of medicine itself will not be affected.Medical and Biological Background

Implanting an invasive device in the body is usually a medical challenge, but is sometimes essential for the betterment of medicine and a more focused problem medical adherence, since adherence to prescribed medication regimens by older adults can vary from 26 - 59 percent [6]. The other problem being patients refuse to even adhere to smart medical dispensing system like in [6]. Both this problems require an invasive device, SmartSense, that encourages medical adherence. Having an invasive device requires us to know how the device reacts to each organ in the digestive tract. Research suggests that sensing capsules can be a serious issue for patients with gut disorders because of the chances in retention of the capsule is 0.33% [4]. They are not suitable to patients with any metal parts in their body and mainly

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pacemakers since they cause a mutual interference [7]. SmartSense device is not harmful for general patients. Innovation

Innovation is a keypoint in the advancement of medicine, whether it being adapting an existing technology or bringing in a new idea. SmartMed, from problem 2, was adapted from a vending machine and toy dispensing system. The pill tagging system was adapted from an existing technology to caterer the needs of smart dispensing [2]. SmartSense was adapted from a simpler device that is used to patch stomach wounds [4]. The device underwent major changes according to the needs of a smart diagnostic system. Features like RFID tagging, connectivity to a user interface, magnetic suspension, biweekly period in the stomach and anchors make SmartSense a better product than preliminary designs available in the market. SmartWatch was added to the design for a better user interface, reducing stigma attached with wearing a medical device and reducing a gap in medical adherence. Feasibility

Interfacing with the already existing SmartMed system is one method of innovation that SmartSense has. Implementing a wearable which communicates with SmartMed allows unparalleled accuracy when comparing to existing diagnostic systems. Most digital medicine monitoring systems on the market today do not relay constant updated information while being able to stay in the body for extended periods. The use of a programmed suspension system allows monitoring of medication for up to two weeks. If the RFID capsule is knocked out of suspension, it can fold into its into an enclosed position and propulse itself and reposition again via magnetic actuation. The tagging system follows the safety framework designated by ISO-10993 [2]. Within the United States set regulations on digital medicine monitoring systems is governed by the FDA’s Center for Devices and Radiological Health (CDRH). Classification of digital systems with the inclusion of software is under class II, complying with premarket review and clinical testing [8]. Failure Analysis

Currently, our device needs to interact with the wearable to communicate with SmartMed. This is due to the size of the pill and the distance restriction being at such a small scale of under five meters. This also means it will require the user to be either wearing or be within five meters of the wearable in order for the signal to send as well as ensuring the wearable is on the same Wifi as SmartMed. Lastly, the RFID does not have a failsafe in case medication is counted twice. Our device is also designed to serve those who are older than age eighteen. People with pacemakers, metal implants and gastric alignments cannot use this device for frequency interference problems may occur. Conclusion

The novelty in the SmartSense system is proven from its accuracy and ease-of-use in which other devices with similar functions are not able to attain. Developing a novel system to deliver medication solves the initial problem but the corollary to this is defined by the issue of proper medication ingestion. The SmartSense aims to ease this with it’s two step verification of continuous monitoring via digital methods.

Figures

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Figure 1 : This is the exploded view of the assembly of SmartMed medical dispenser. It was modified from problem 2 to accommodate the needs of pill tagging by adding an arm pictured in [ Fig 5]. The device is 1 cubic feet.

Figure 2: This is an assembly of the Figure 3: This is a model of a smartwatchSmartSense device, that counts the that get signals from the SmartSense device number of medicine intake in a patient in [Fig 2]. It has Wi-Fi connectivity to go it has two sensors, a magnet and a with SmartSense device [Fig 1]. gastric acid powered battery. The anchors on the side help it anchor in the stomach.The dimensions 0.64mm x 0.45mm x 0.9mm.

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Figure 4: This is a sample medicine with a pill tag on, dispensed by SmartMed. The size of the pill tag is 1mm x 1mm x 0.3mm. It is pressed on to the medicine using the arm in [Fig 5].

Figure 5: This part is the arm that is assembled onto the SmartMed dispenser and is responsible for tagging each pill. The top attached to the wall of the SmartMed and the bottom is what presses the tag on. It is also assisted by other arms in the dispenser, part of problem 2.

Figure 6: This figure is the primary inspiration of our device, SmartSense. It was primarily researched at MIT [origami paper]. The primary function is to patch wounds and does not stay in the digestive system for longer than a day.

References

[1] Anonymous "Cost of medication nonadherence associated with diabetes, hypertension, and dyslipidemia," Medical Benefits, vol. 29, (9), pp. 3, 2012. [Online serial]. Available: https://www.researchgate.net/profile/Sharon_Frazee/publication/237065869_Cost_of_medicatio

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n_nonadherence_associated_with_diabetes_hypertension_and_dyslipidemia/links/00b7d53b54bedbcab1000000.pdf. [Accessed May 3, 2018].

[2] H. Hafezi et al, "An Ingestible Sensor for Measuring Medication Adherence," Tbme, vol. 62, (1), pp. 99-109, 2015. [Online serial]. Available: https://ieeexplore.ieee.org/document/6861446. [Accessed May 3, 2018].

[3] H. Rajagopalan and Y. Rahmat-Samii, "Ingestible RFID bio-capsule tag design for medical monitoring," in 2010, pp. 1-4.

[4] S. Miyashita et al, "Ingestible, controllable, and degradable origami robot for patching stomach wounds," in 2016, pp. 909-916.

[5] P. Bhagwat, "Bluetooth: technology for short-range wireless apps," Mic, vol. 5, (3), pp. 96-103, 2001. [Online serial]. Available: https://ieeexplore.ieee.org/document/935183. [Accessed May 4, 2018].

[6] B. Reeder, G. Demiris and K. D. Marek, "Older adults' satisfaction with a medication dispensing device in home care," Informatics for Health and Social Care, vol. 38, (3), pp. 211-222, 2013. [Online serial]. Available: http://www.ncbi.nlm.nih.gov/pubmed/23323721. [Accessed May 4, 2018].

[7] Kourosh Kalantar-zadeh et al, "Ingestible Sensors," ACS Sensors, vol. 2, pp. 468-483, 2017. [Online serial]. Available: https://pubs.acs.org/doi/pdf/10.1021/acssensors.7b00045. [Accessed May 4, 2018].

[8] E. Elenko, A. Speier and D. Zohar, "A regulatory framework emerges for digital medicine," Nature Biotechnology, vol. 33, (7), pp. 697, 2015. [Online serial]. Available: http://www.ncbi.nlm.nih.gov/pubmed/26154006. [Accessed May 4, 2018].