Description
ABSTRACT
Diabetes mellitus (DM) is one of the most prevalent diseases and easily lead to serious complications. Glycosylated hemoglobin (HbA1c), an emerging biomarker for reliable monitoring of DM is commonly detected by bench-top immunoassays, which are labor-intensive and time-consuming. As an advance to existing methods, a microfluidic platform capable of performing automated immunoassay for HbA1c detection within 25 minutes is presented in this work. The microfluidic assay was able to detect HbA1c from human whole blood samples and delivered similar performance as its bench-top counterpart. The developed microfluidic chip is therefore promising for rapid detection of HbA1c for monitoring DM.
TABLE OF CONTENTS
COVER PAGE
TITLE PAGE
APPROVAL PAGE
DEDICATION
ACKNOWELDGEMENT
ABSTRACT
CHAPTER ONE
- INTRODUCTION
- BACKGROUND OF THE PROJECT
- PROBLEM STATEMENT
- AIM / OBJECTIVE OF THE STUDY
- APPLICATION OF THE STUDY
- SIGNIFICANCE OF THE STUDY
- SCOPE OF THE STUDY
- PURPOSE OF THE STUDY
- PROJECT ORGANISATION
CHAPTER TWO
LITERATURE REVIEW
- OVERVIEW OF DIABETES MELLITUS
- BLOOD GLUCOSE MONITORING
- OVERVIEW OF BLOOD GLUCOSE METERS
CHAPTER THREE
3.0 MATERIALS AND METHOD
- CHEMICAL AND MATERIALS
- FABRICATION OF LPGS IN SMALL-DIAMETER SINGLE-MODE FIBER (SDSMF)
- PREPARATION OF THE GLUCOSE SENSING FILMS BY LBL SELF-ASSEMBLY TECHNIQUE
- FABRICATION OF THE MICROFLUIDIC CHIP
- BIOSENSOR TESTS
- CHARACTERIZATION
CHAPTER FOUR
4.0 RESULT AND DISCUSSION
- RI SENSING PROPERTY OF SDSMF-LPGS
- (PEI/PAA)9(PEI/GOD)1 MULTILAYER SENSING FILM PREPARATION
- SDSMF-LPG GLUCOSE BIOSENSORS
- FABRICATION AND TESTS OF THE MICROFLUIDIC CHIP
- CHAPTER FIVE
- CONCLUSION
- REFERENCES
CHAPTER ONE
1.0 INTRODUCTION
1.1 BACKGROUND OF THE STUDY
Diabetes mellitus (DM) affects nearly 10 percent of adults worldwide and has become one of the most prevalent diseases in the modern world. Often leading to serious complications such as cardiovascular diseases and nephropathy, diabetes therefore not only presents a health burden but also an economic burden. Toward the prevention and the proper treatment of diabetes, monitoring and thereby maintaining the blood glucose is critical. Although direct measurement of blood glucose using the glucose meter has been a ubiquitous approach, such measurement can easily fluctuate due to intake of food and drugs, as well as the physical condition of the patient. Recently, glycosylated hemoglobin (HbA1c) has emerged as an accurate indicator for diabetes [1]. It provides an average value of blood glucose over the previous 2-3 months. Existing techniques to measure HbA1c, such as immunoassays, however, are relatively expensive, labor- intensive and time-consuming. To tackle these problems and enable wide-spread use of HbA1c-based monitoring for diabetes, this study reports a microfluidic system that automatically detects and quantifies clinically-relevant HbA1c concentrations from human blood samples.
Highly sensitive and rapid detection of glucose content has become one of essential biomedical diagnostic technologies. For instance, two main causes of diabetes mellitus are insulin deficiency and hyperglycemia in human body, and both of the two parameters can be reflected by blood glucose concentrations [1,2].
In this paper, we demonstrate an LPG biosensor fabricated in a small-diameter single-mode fiber (SDSMF) for glucose sensor development and on-chip integration, as shown in Fig. 1. A hybrid sensing film using multi-layer poly (ethylenimine) (PEI) and poly (acrylic acid) (PAA) supporting film and a negatively charged glucose oxidase (GOD) outer layer is deposited on the side surface of LPG for glucose sensing and signal enhancement. The SDSMF-LPG biosensor is then integrated into a microfluidic chip for fast and low-sample-consumption glucose analysis. Experimental results reveal that the fabricated LPG glucose sensor can detect ultralow concentration of glucose (~10−9 M). The performances of the biosensor, in terms of response time and detection range, are significantly improved after integrated into the microfluidic chip.
1.2 PROBLEM STATEMENT
The glucose biosensor was firstly demonstrated by using electrochemical glucose enzyme electrodes [3]. Thereafter, many electronic techniques based on glucose oxidase (GOD) have been proposed for glucose biosensor development [4–6]. For example, the conductive polypyrrole encapsulated by pHEMA hydrogel was adopted as matrix for GOD, which was then deposited on Pt electrode for glucose detection [4]; GOD-graphene-chitosan nanocomposite was demonstrated as active component and glassy carbon was used as electrode for glucose biosensor fabrication [5]. However, the electron transfer between GOD and electrode is not efficient. Moreover, those glucose biosensors are usually too bulky and costly for daily use and their sample consumption is relatively high.
One of potential solutions to these problems is to use microfluidic chips due to their advantages of compactness, low-sample consumption, and low cost [7,8]. Moreover, microfluidic chip technology offers a platform to integrate sensors with functional components (e.g. microfluidic mixers) to achieve the lab-on-a-chip analysis system [9]. Recently, it was demonstrated electrochemical glucose biosensors can be integrated into microfluidic channels to develop easy-handle, low-cost, and portable microfluidic chips [10–13]. However, electroactive interference problems often appear in electrochemical sensors because some endogenous reducing species (e.g. ascorbic and uric acids) and drugs (e.g., acetaminophen) are electroactive [1].
The limitation can be overcome by using optical fiber sensor technology due to its well-known immunity to electromagnetic interferences [14–16]. For instance, Tiwari et al. [15] adopted GOD immobilized long-period grating (LPG) sensor for detection of glucose; Yang et al. [16] proposed a nanoporous TiO2/polyion film coated LPG sensor to improve the detection limitation (~10−7 M); Luo et al. [17] suggested GOD modified tilted fiber grating sensor for highly sensitive detection of low glucose concentraion. Therefore, a promising solution is to integrate fiber-optic sensor with microfluidic technology to develop high-performance glucose sensing devices.
Fig. 1
(a) Schematic design of the optical fiber biosensor integrated microfluidic chip: ① are two inlets, ② is outlet, ③ is a spiral mixture, ④ are optical fibers and ⑤ is the embedded LPG sensor. (b) The mode coupling and optical resonance in the LPG biosensor. (c) Working mechanism of the multilayer film for glucose sensing and signal enhancement.
1.3 AIM / OBJECTIVE OF THE STUDY
The aim of this work is to discuss an optical fiber sensor integrated microfluidic chip as used for ultrasensitive detection of glucose.
1.4 APPLICATION OF THE STUDY
An optical fiber glucose biosensor integrated microfluidic chip is used for both healthcare and clinical diagnosis.
1.5 SIGNIFICANCE OF THE STUDY
The use of microfluidic chips due to their advantages of compactness, low-sample consumption, and low cost.
1.6 SCOPE OF THE STUDY
An optical fiber sensor integrated microfluidic chip is presented for ultrasensitive detection of glucose. A long-period grating (LPG) inscribed in a small-diameter single-mode fiber (SDSMF) is employed as an optical refractive-index (RI) sensor. With the layer-by-layer (LbL) self-assembly technique, poly (ethylenimine) (PEI) and poly (acrylic acid) (PAA) multilayer film is deposited on the SDSMF-LPG sensor for both supporting and signal enhancement, and then a glucose oxidase (GOD) layer is immobilized on the outer layer for glucose sensing. A microfluidic chip for glucose detection is fabricated after embedding the SDSMF-LPG biosensor into the microchannel of the chip. Experimental results reveal that the SDSMF-LPG biosensor based on such a hybrid sensing film can ultrasensitively detect glucose concentration as low as 1 nM. After integration into the microfluidic chip, the detection range of the sensor is extended from 2 µM to 10 µM, and the response time is remarkablely shortened from 6 minutes to 70 seconds.
1.7 PURPOSE OF THE STUDY
Blood glucose monitoring reveals individual patterns of blood glucose changes, and helps in the planning of meals, activities, and at what time of day to take medications.
Also, testing allows for quick response to high blood sugar (hyperglycemia) or low blood sugar (hypoglycemia). This might include diet adjustments, exercise, and insulin (as instructed by the health care provider).[2]
1.8 PROJECT ORGANISATION
The work is organized as follows: chapter one discuses the introductory part of the work, chapter two presents the literature review of the study, chapter three describes the methods applied, chapter four discusses the results of the work, chapter five summarizes the research outcomes and the recommendations.
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