Team:NYMU-Taipei/Project

Project Overview
After ingesting our BacToKidney capsule, it passes the through stomach without taking any action, nor being digested, and proceeds to the small intestine. Once in the small intestine, the pH Sensor detects the change in pH and activates the clearance processes of Urea, Phosphate, and Guanidine from the body. To allow itself more time to perform its tasks, the pH Sensor also activates the Attachment process, making the capsule attach itself to the small intestine. After a pre-selected amount of time has passed (controlled by the time regulating oscillators), the capsule detaches itself from the small intestine and exits the body.

Sales Pitch
Kidney's are a really important part of our bodies. But what happens if they break? There are two choices: get a new one, or undergo hemodialysis. Hemodialysis prolongs life, yet it really is just another form of torture. To undergo hemodialysis, one has to go to the hospital every few days for hours at a time while a machine cleans out your blood. What's life without enjoyment? Staying tied within range of a hospital, unable to travel or go on vacation anywhere easily. Some have made a "portable" dialysis machine, but as you can see, this portable dialysis machine requires nothing less than than a small vehicle to transport it along. But what if there was the possibility of dialysis without staying tied to a hospital? if there was no need to bring heavy machinery everywhere you go? What if there was something more portable ... something you could ingest ... something ... convenient? Our project BacToKidney tries to realise this dream. We designed an ingestable bacteria capsule which would clean out the waste products in your bloodstream without the need of a machine. Think about the possibilities. Not needing to goto hospital as often. Being able to travel to faraway places. Freedom. As if life can be enjoyed once again. Wouldn't that be wonderful ...

Design
Our design was split into four parts:
 * The pH Sensor -- a promoter (pNhaA) which activates in an alkaline pH of around 7 to 8, the pH of the small intestine.
 * The Attachment -- A mechanism to allow attaching to the small intestine.
 * The regulation of time -- where we create a timer to control the time before detaching from the small intestine
 * The removal of the waste products -- the removal of Urea and Guanidine; and the balancing of Phosphate.

Delegation
Our subteams were split in this manner:


 * pH Sensor
 * Attachment and Detachment
 * Time Regulation
 * Removal of Urea (part of the Waste Removal)
 * Removal of Guanidine (part of the Waste Removal)
 * Balancing of Phosphate (part of the Waste Removal)

Issues on Human Practice
Before animal or human trials, the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) can be applied as a semi-realistic environment for tests including

Toxicity and Immunoresponse estimation

 * In this competition, we use E. coli as chassis to verify the functions of each components in our system and prove the concept of our design
 * A non-toxic or food-grade chassis (e.g. lactic acid bacteria, mutant E. coli strain) could be good candidates for following up trials in animal or human

Dosage control
We have designed three waste removal devices in our system. For patients with different medical requirements, it is necessary to estimate the dosage effect before practical use. See also QFCS (Quantitative Functional Calibration System). The dosage conversion reference can offer a guide of safety to give appropriate treatments to patients requiring different medical cares.

Related Works

 * The Laboratory of Microbial Ecology and Technology
 * In Vitro and In Vivo Assessment of Intraintestinal Bacteriotherapy in Chronic Kidney Disease, ASAIO J. 2006
 * In Vivo and in Vitro Degradation of Urea and Uric Acid by Encapsulated Genetically Modified Microorganisms, Tissue Engineering 2004
 * Artificial cells containing genetically engineered E. coli DH5 cells for urea and ammonia removal in kidney and liver failure, Engineering in Medicine and Biology Society, IEEE 17th Annual Conference 1995 and fulltext
 * Artificial Cells for Bioencapsulation of Cells and Genetically Engineered E. coli, Methods in Molecular Biology 2008 (Thomas M. S. Chang and Satya Prakash)
 * Artificial Cell Biotechnology for Medical Applications, Blood Purif 2000 (Thomas Ming Swi Chang)

Acknowledgments

 * Kondo Takao (Graduate School of Science, Nagoya University)
 * Susan Stephens Golden (Department of Biology, Texas A&M University)
 * Shie-Liang Hsieh (Department of Microbiology and Immunology, National Yang Ming University)
 * Ueng-Cheng Yang (Institute of Biomedical Informatics, National Yang Ming University)
 * Ann-Ping Tsou (Institute of Biotechnnology in Medicine, National Yang Ming University)
 * Ying-Chieh Tsai (Institute of Biochemistry and Molecular Biology, National Yang Ming University)
 * Wailap Victor Ng (Institute of Biotechnnology in Medicine, National Yang Ming University)
 * Yueh-Hsing Ou (Institute of Biotechnnology in Medicine, National Yang Ming University)