Abstract

This study is based on our iGEM (international genetically engineered machine) 2019 competition project in which an in vitro model was established to simulate the human monitoring and regulation of blood glucose level using the “liver-on-a-chip” and a genetically engineered bacterium capable of producing proinsulin efficiently. The microfluidic device is able to accommodate cellular chassis loaded with biological parts for diabetic treatment. In addition, electrochemical biosensors were designed to detect the differential glucose concentration from the both chambers of the organ chip. The model can test different chemicals and organs, when the components in the channels and cells are altered. We have thus accomplished an in vitro model of how the proinsulin generated by engineered bacteria works on liver cells. In the near future, our research paradigm will be shifted to bacterial implantation in the human intestines to replace pancreas for the automatic secretion of insulin for diabetic patients.

Highlights

  • A World Health Organization revealed that there were already 422 million diabetics in 2014 and the number continued to rise each year

  • Phases of type 2 diabetes can be treated with dietary control and regular exercise; the treatment to type 1 diabetes is dependent on insulin injection which requires patients to monitor their blood sugar level and inject insulin once or several times a day [2]

  • Previous research has shown that intravenous injections of proinsulin in animal or human result in a decrease in blood glucose

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Summary

Introduction

A World Health Organization revealed that there were already 422 million diabetics in 2014 and the number continued to rise each year. If we are to fight against diabetes, we need to first understand its mechanism Healthy people use their pancreas to secret enough insulin for effective cellular glucose consumption, so their blood sugar level remains low. Diabetic patients can neither produce insulin by their pancreas at all, nor produce it enough, so that their glucose in blood cannot be used by human body. Previous research has shown that intravenous injections of proinsulin in animal or human result in a decrease in blood glucose. This suggests that proinsulin has similar functions of lowering blood glucose level as insulin.

Methods and Materials
Genes and Transformation Vectors
Spacer Peptide
P43 Promoter
Gene Transformation
Sensors
Microfluidic device for construction of liveron-a-Chip
Hardware
Software
Biological Design
Construction of Chassis
Temperature Negative Feedback Control of Glucose
Design
Testing
Liver-on-a-chip
Design of liver-on-a-chip
Dual Sensor
Cell cultures in the liver-on-a-chip
Electrochemical Simulation
Mathematical Model
Glucose regulation
Fabrication of liver-on-a-chip
Conclusions
Full Text
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