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Ingestible Medical Devices

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In recent years, the ingestible electronic pill has been shown to be a clinically relevant technology platform, with biomedical applications such as drug delivery, optical imaging for disease diagnosis, and more. Our interdisciplinary work in this area aims to combine circuits and sensing techniques to expand the capabilities of ingestible capsules and enable new diagnostic, treatment, and scientific study applications.

Capsule Ultrasound (CUS)
In collaboration with Professor Butrus T. Khuri-Yakub's research group, we are developing a Capsule Ultrasound (CUS) device – a disposable wireless imaging sensor. The CUS device aims to bring ultrasound technology to a pill that can be swallowed at the convenience of the patient. By emitting and receiving ultrasound waves, an ultrasonic sensor array around the pill takes images of the walls of the GI tract. Unlike optical endoscopes that can only examine the surface of the GI tract, the CUS device simultaneously images deeper layers and even surrounding organs. Then the captured images are wirelessly transmitted to a device worn by the patient, such as a smartphone, and can be used by medical experts for rapid screening for lesions, cancerous tissue, and other diseases.

Towards this goal, we have fabricated and successfully tested the core components of the first generation CUS system: cylindrical capacitive micromachined ultrasonic transducer (CMUT) array, imaging circuitry with 128 channels and beamforming capability, and wireless transmitter with a 10 Mbps data rate [1-3]. Once integrated, we expect the CUS device to produce 4 frames/s of valuable medical images and operate wirelessly through more than 10 cm of body tissue. We envision this capsule platform could in the future enable a vast array of exciting new biomedical and consumer applications on and inside the human body.

Gut Microbiome Redox sensor
In collaboration with Professor Justin L. Sonnenburg (Microbiology/Immunology) we are developing an in vivo wireless sensor for monitoring gastrointestinal tract redox states. A perturbed gut microbiome has recently been linked with multiple disease processes ranging from Inflammatory Bowel Disease to enteric infections. An emerging hypothesis is that disease-associated microbiomes share a common feature: an altered chemical landscape in the gut with a higher level of environmental oxidation [4,5]. However, researchers currently lack tools that can provide in vivo, quantitative, and real-time insight into oxidation processes and associated host-microbe interactions. The proposed sensor measures oxidation-reduction potential (ORP) to measure the gut oxidation state of a laboratory animal during dietary, microbial, and genetic manipulation.

We have built a prototype of our sensor designed as an implant, powered and conveniently interrogated via ultrasonic waves [6]. We engineered the sensor electronics, electrodes, and encapsulation materials for robustness in vivo, and integrated them into a biocompatible package that endures autoclave sterilization. As a proof-of-concept, we performed in vivo ORP measurement over 12 days in a live rat cecum, which to our knowledge has not been previously demonstrated. The presented implant platform paves the way for convenient experimental testing of biological hypotheses, offering new opportunities for understanding gut redox pathophysiology mechanisms, and facilitating translation to disease diagnosis and treatment applications.

Capsule Ultrasound (CUS) device - towards miniaturization of medical ultrasound, enabling rapid screening of the gastrointestinal tract with a disposable ingestible device.

CUS components and block diagram.
Operation of cylindrical ultrasonic transducer array on capsule and example of resulting image.
Fabricated wireless transmitter chip for communicating captured images, an example of its measured output spectrum during transmission, and conceptual wireless operation inside the body.
We have demonstrated a gut sensor that measures the balance of oxidants and reductants (the ORP) produced by the interplay of host, microbe, and diet. The sensor is implanted in the gastrointestinal tract of rodents and communicates externally to the same ultrasonic receiver powering the device.
(a) Gut microbiome sensor photograph, and breakdown of its construction. (b) Simplified system block diagram.

[1] J. Wang, F. Memon, G. Touma, S. Baltsavias, J. H. Jang, C. Chang, M. F. Rasmussen, E. Olcott, R. B. Jeffrey, A. Arbabian, and B. T. Khuri-Yakub, "Capsule Ultrasound Device: Characterization and Testing Results," IEEE IUS, Sept. 2017.

[2] F. Memon, G. Touma, J. Wang, S. Baltsavias, A. Moini, C. Chang, M. F. Rasmussen, A. Nikoozadeh, J. W. Choe, E. Olcott, R. B. Jeffrey, A. Arbabian, and B. T. Khuri-Yakub, "Capsule Ultrasound Device: Further Developments," IEEE IUS, Sept. 2016.

[3] F. Memon, G. Touma, J. Wang, S. Baltsavias, A. Moini, C. Chang, M. F. Rasmussen, A. Nikoozadeh, J. W. Choe, A. Arbabian, R. B. Jeffrey, E. Olcott, and B. T. Khuri-Yakub, “Capsule Ultrasound Device,” IEEE IUS, Oct. 2015.

[4] Y. Litvak, M. X. Byndloss and A. J. Bäumler, “Colonocyte metabolism shapes the gut microbiota,” Science, 362, 2018.

[5] E. L. Campbell and S. P. Colgan, “Control and dysregulation of redox signalling in the gastrointestinal tract,” Nat. Rev. Gastroenterol. Hepatol., 16, 2018.

[6] S. Baltsavias, W. Van Treuren, M. J. Weber, J. Charthad, S. Baker, J. L. Sonnenburg and A. Arbabian, "In Vivo Wireless Sensors for Gut Microbiome Redox Monitoring," arXiv preprint, arXiv:1902.07386, 2019.