BioMEMS

Science and Engineering Perspectives

Simona Badilescu, Muthukumaran Packirisamy

• Publisher: CRC Press
• Year: 2016
• ISBN:
  9781439893494
• Edition: 1
• Topic: Medicine
• Subtopic: Biotechnology in Medicine

Written to cover often overlooked areas in the field of bioMEMS, this volume bridges topics related to biomolecules and complex biological entities with those directly related to the design, fabrication, and characterization of the devices. Unlike other references, this text aids with the fundamental physicochemical understanding of biological processes relevant to the performance of various biosensing devices. Accessible to seniors and graduate students enrolled in engineering programs, the book includes problems in each chapter as well as case studies to provide real-life examples.

1 Introduction

1.1 INTRODUCTION TO BIOMEMS

The term microelectromechanical systems (MEMS) was coined in the 1980s to define devices that were fabricated using microfabrication techniques and whose primary function was not electronic but mainly mechanical. Within a short span of time, the field of MEMS exposed its immense potential to impact every aspect of human life.

A variety of areas, like aerospace, communication, medical, sensing, and actuation, started enjoying the advantages of miniaturization with MEMS technology or microsystem technology. As a result, the field of MEMS evolved into an enabling technology in the mid-1990s and gave rise to the creation of many subdisciplines, such as optical MEMS, radio frequency (RF) MEMS, power MEMS, etc., depending upon the focus of application. In this line, the field of BioMEMS was created with a focus on biological and chemical applications.

The concept of integrating biochemical analysis with microelectromechanical systems (MEMS) is involved in the new field of BioMEMS, which is undergoing tremendous growth in a multitude of applications. The applications spectrum covers from tissue engineering to pro-teomics. Some of the applications include cell culture, cell sorting, cell manipulation, stem cell growth, separation and mixing of biological and chemical fluids, enzymatic reactions and gene isolation and transformation, DNA purification, antigen-antibody interaction, protein level interaction, drug diagnosis and delivery, therapeutics, chemical and biosensing, etc. The important recent applications include point-of-care (POC) in vitro diagnostics, and synthesis of nanoparticles using BioMEMS.

The field of BioMEMS inherits all the advantages of miniaturization, such as small sample volume, scalability, integration of multiple functions and fields, low cost, low power consumption, etc. As a result, the microsystems facilitate the implementation of many laboratory works at the microchips that are millimeters to centimeters in size. Some of the standard laboratory tasks that can be implemented under a microenvironment include sample preparation, mixing, separation, diagnosis, sensing, manipulation, control, delivery, data acquisition, and analysis. When some of the laboratory functions out of a process are integrated at the microchip, the devices are called lab-on-a-chip (LOC). The concept of LOC was demonstrated by S. C. Terry et al. in 1979¹ with the development of a silicon-chip-based gas chromatographic analyzer. Manz et al.² introduced the concept of micro total analysis system (µTAS) in 1990, by developing a device that conducts all the steps of a process. µTAS is generally considered to incorporate all the operations needed in a process, involving sample preparation. Even though µTAS is a subset of LOC, it involves many functions and integrates many domains, such as micromechanical, microfluidic, microelectronics, microphotonics, etc. µTAS can also integrate moving elements, such as micropumps, microvalves, etc. LOC and µTAS will be used interchangeably in this book. Biomedical technologies contribute to the use of LOCs in healthcare of various specialties, ophthalmology, cardiology, anesthesiology, and immunology. For example, such LOCs combine a number of biological functions, such as enzymatic reactions, antigen-antibody conjugation, and DNA/gene probing, in addition to microfluidic function, such as sample dilution, pumping, mixing, metering, incubation, separation, and detection in micron-sized channels and reservoirs. Lab-on-a-chip devices aim to address a wide range of life science applications, including drug discovery and delivery as well as clinical and environmental diagnostics. The integration and automation capabilities of LOC can improve the reproducibility of results, reduce test time, and eliminate preparation errors that may occur in the intermediate stages of an analytical procedure.

BioMEMS devices are defined as the devices or microsystems that are fabricated with methods inspired from micro- and nanotechnologies and are used for many processes involving biological and chemical species.³

BioMEMS may involve in-parts or a combination of (1) microchannels, microchambers, etc., for handling a small volume of liquids in the range of microliters to nanoliters; (2) micromechanical elements, such as microvalves, micropumps, microcantilevers, microdiaphragms, etc.; (3) micro-electrical elements such as electrodes and heaters; and (4) microphotonic elements, such as waveguides, gratings, interferometers, etc., to handle bio or chemical species with an elaborate integration feasibility. BioMEMS offers the following advantages: portability, scalability, reliability, reduced sample/reagent volume, low power consumption, high throughput, integrability, disposability, batch fabrication, low cost, high sensitivity, reduced test time, etc. BioMEMS devices combine a biological recognition system called a bioreceptor with a physical or chemical transducer to selectively and quantitatively detect the presence of specific compounds in a given external environment. A bioreceptor is a biological molecular species (e.g., antibody, enzyme, protein, or nucleic acid) or a living biological system (e.g., cells, tissue, or whole organisms) that undergoes a biochemical mechanism for recognition. The interaction of an analyte with a bioreceptor produces an effect to be measured by the transducer, which converts the information into a measurable effect, such as an electrical or optical signal.

Lab on a chip is characterized by some level of integration of different functions, and it can be used to perform a combination of analyses on a single miniaturized device, for biological and clinical assays. Most of the key application areas of this technology belong to the areas of life science research (genomics, pharmacogenomics, and proteomics), drug delivery, and point-of-care diagnostics, and they offer the advantages of integrating sample handling and preparation, mixing, separation, lysing of cells, and detection.

Biosensors and biochips can be classified by either their bioreceptor or their transducer type. Comprised of microarrays of genetic, protein, or cellular materials on microfluidic devices, these miniature platforms can perform parallel analysis of large data. Lab-on-a-chip can integrate many operations, including sample preparation, detection, and analysis on a single chip. It is also useful in drug discovery, target identification and validation, toxicology, and clinical drug safety.

1.2 APPLICATION AREAS

Research in BioMEMS covers a wide range, from diagnostics, DNA, and protein microarrays, to novel materials for BioMEMS, microfluidics, surface modification, etc. In addition, BioMEMS also finds many applications in the chemical, healthcare, biotechnological, and manufacturing industries.

The emerging applications for BioMEMS include agricultural and food engineering areas. DNA microarrays have become the most successful example of the integration among microelectronics, biology, and chemistry. Similarly, protein and antibody arrays can identify disease-specific proteins with enormous medical, diagnostic, and commercial potential as disease markers or drug targets. With the recent thrust in genomics and proteomics technologies, many new gene products and proteins are being discovered almost daily, and it has become a difficult task to analyze experimental data. In such situations, array-based integrated BioMEMS chips and microfluidics hold great potential to analyze systematically the proteins and to determine protein-protein or protein-DNA interactions. In the case of protein chips, protein is arrayed into many spots using robots, and each spot is addressed by other affinity proteins. The binding between recognized proteins or antigen-antibody has traditionally been detected by fluorescence-based methods. But it can also be detected by changes in surface plasmon resonance (SPR) due to changes in surface refractive index, or in a mechanical way of detecting the changes in structural properties due to interaction. For example, enzyme-linked immunosorbent assay (ELISA) type assays use selective bonding to antibodies immobilized on microfabricated surfaces and detect the bioaffinity binding using electrical or optical detectors. Several accomplishments in using BioMEMS with various modes of detection technologies have been reported. A current goal of BioMEMS research is identification and manipulation at the molecular/cellular level. Microfluidics based lab-on-a-chip devices has proved useful for realizing single molecule/ cell detection also.

Figure 1.1 BioMEMS at the intersection of science and engineering.

1.3 INTERSECTION OF SCIENCE AND ENGINEERING

The BioMEMS devices are made of silicon, glass, or polymer materials to produce highly functional miniaturized devices. A major driving force behind this is the rapidly emerging biochip market, wherein original MEMS techniques are integrated with advanced techniques from molecular biology, physics, chemistry, and data analysis, as shown in Figure 1.1.

Expansion of the biochip sector is predicted to be one of the key drivers for the growth of the microsystems market, and to have a profound impact on many aspects of life science industries. BioMEMS chips also promise to be among the most important pharmaceutical research and development tools in the postgenomic era.

Diagnostics applications form the largest part of BioMEMS applications. A very large and increasing number of BioMEMS devices for diagnostic applications have been developed and presented in the literature by many groups within the last decade. These devices are used to detect cells, microorganisms, viruses, proteins, DNA and related nucleic acids, and many small molecules of biochemical interest. BioMEMS devices for cell characterization ...

Table of contents

• Cover
• Halftitle
• Title Page
• Copyright Page
• Dedication
• Table of Contents
• Preface
• The Authors
• Chapter 1 Introduction
• Chapter 2 Substrate Materials Used in BioMEMS Devices
• Chapter 3 Biomolecules and Complex Biological Entities: Structure and Properties
• Chapter 4 Engineering of Bioactive Surfaces
• Chapter 5 Methods of Study and Characterization of Surface-Modified Substrates
• Chapter 6 Biosensing Fundamentals
• Chapter 7 Fabrication of BioMEMS Devices
• Chapter 8 Introduction to Microfluidics
• Chapter 9 BioMEMS
• Index