Microfluidics for Pharmaceutical Applications

From Nano/Micro Systems Fabrication to Controlled Drug Delivery

Hélder A. Santos, Dongfei Liu, Hongbo Zhang

• Publisher: William Andrew
• Year: 2018
• Print ISBN: 9780128126592
• eBook ISBN: 9780128126608
• Topic: Technology & Engineering
• Subtopic: Physical & Theoretical Chemistry
• Index: Technology & Engineering

Microfluidics for Pharmaceutical Applications: From Nano/Micro Systems Fabrication to Controlled Drug Delivery is a concept-orientated reference that features case studies on utilizing microfluidics for drug delivery applications. It is a valuable learning reference on microfluidics for drug delivery applications and assists practitioners developing novel drug delivery platforms using microfluidics. It explores advances in microfluidics for drug delivery applications from different perspectives, covering device fabrication, fluid dynamics, cutting-edge microfluidic technology in the global drug delivery industry, lab-on-chip nano/micro fabrication and drug encapsulation, cell encapsulation and delivery, and cell- drug interaction screening.These microfluidic platforms have revolutionized the drug delivery field, but also show great potential for industrial applications.- Presents detailed coverage on the fabrication of novel drug delivery systems with desired characteristics, such as uniform size, Janus particles, and particular or combined responsiveness- Includes a variety of case studies that explain principles- Focuses on commercialization, cost, safety, society and educational issues of microfluidic applications, showing how microfluidics is used in the real world

Section 1

Principle of Microfluidics

Chapter 1

Lab-on-a-chip technology and microfluidics

Antonio Francesko⁎^,a; Vanessa F. Cardoso⁎^,†,a; Senentxu Lanceros-Méndez^{‡,§ ⁎} Center of Physics, University of Minho, Braga, Portugal
^† CMEMS-UMinho, University of Minho, DEI, Guimarães, Portugal
^‡ BCMaterials, UPV/EHU Science Park, Leioa, Spain
^§ Ikerbasque, Basque Foundation for Science, Bilbao, Spain
^a These authors equally contributed to this work.

Abstract

This chapter presents an overview of the main topics related to microfluidics for pharmaceutical applications. It begins with a general introduction on lab-on-a-chip technology and microfluidics, in which the main definitions, concepts, and characteristics are presented. Further, the main materials and processing techniques used for the development of microfluidic systems are introduced. Finally, the most representative applications are discussed. Applications are focusing on the areas of drug development, drug delivery and diagnosis, cell-based devices, and organs-on-a-chip devices, the latest step toward whole-body models. Thus, a complete overview in the area is provided, followed by a summary and outlook on open questions and future trends.

Keywords

Microfluidics; Pharmaceutical applications; Lab-on-a-chip; Organ-on-a-chip; Drug testing

Chapter Outline

• 1. Introduction
• 2. Definition, Main Concepts and Characteristics
• 3. Microfluidic Technology for Pharmaceutical Applications
• 4. Materials and Processing Techniques
  • 4.1. Silicon and Glass
  • 4.2. Polymers
  • 4.3. Paper
• 5. Representative Applications
  • 5.1. Microfluidic Technology for Drug Development, Drug Delivery and Diagnostics
  • 5.2. Cell-Based Devices
  • 5.3. Organs-On-A-Chip, A Step Toward Whole Body Models
• 6. Summary and Outlook
• Acknowledgements
• References
• Further Reading

Acknowledgements

The authors thank the Fundação para a Ciência e Tecnologia (FCT) for the financial support under the framework of the Strategic Funding UID/FIS/04650/2013, project PTDC/EEI-SII/5582/2014, and project UID/EEA/04436/2013 by FEDER funds through the COMPETE 2020—Programa Operacional Competitividade e Internacionalização (POCI) with the reference project POCI-01-0145-FEDER-006941. Funds provided by FCT in the framework of EuroNanoMed 2016 call, project LungChek (ENMed/0049/2016), are also gratefully acknowledged. VFC and AF also thank the FCT for the postdoctoral grants SFRH/BPD/98109/2013 and SFRH/BPD/104204/2014, respectively. Finally, the authors acknowledge funding by the Spanish Ministry of Economy and Competitiveness (MINECO) through the project MAT2016-76039-C4-3-R (AEI/FEDER, UE) and from the Basque Government Industry Department under the ELKARTEK program.

“Everything in excess is opposed to nature”

Hippocrates (460–377 BC)

1 Introduction

Since the introduction of a miniaturized gas chromatography analyzer on a silicon wafer in the 1970s by Terry et al. [1] and most prominently since the conceptual work on a miniaturized total chemical analysis systems by Manz et al. in 1990 [2], the field of micro total analysis systems (μTAS) or lab-on-a-chip (LOC) technology has been under intensive development in many biotechnological areas spanning from basic theoretical models and academic proof-of-concept studies to commercial applications. LOC are ideally described as miniature versions of their macroscale counterparts and therefore usually integrate all the component units of a complete laboratory essay [3]. The term microfluidic is generally used to describe the precise control and manipulation of small volume of fluids on a micrometer scale, which is the basis of LOC systems. The attractiveness of such miniaturized systems can be attributed in large part to its size effect, which allows portability, low consumption of sample/reagents and power, and short assay time. Further, it is associated to some unique physical phenomena that emerge at such scale and bring numerous benefits in pharmaceutical applications from the early drug discovery and screening stage to the final targeted and controlled delivery stage, as will be addressed later [4]. The high interdisciplinarity of this technology has received inputs from a large spectra of researchers from different areas of expertise in order to develop and apply microfluidics in a wide range of (bio)technological applications, such as clinical diagnostic [5], proteomics [6], cell and tissue engineering [7], pharmacology [8], and environmental monitoring [9], among others [10,11]. The value of this technology is demonstrated by the growing number and improved quality of published papers [12]. According to the ISI Web of Science, about 45,000 of documents related to microfluidics have been published since 2000 being almost 10% related to pharmaceutical applications (Fig. 1.1).

Fig. 1.1 Published items related to “microfluidics” by year since 2000. Data from ISI Web of Science.

This strong growth over the years along with the potential to produce revolutionary and practical miniaturized devices has led to the emergence of a number of companies dedicated to microfluidics and LOC for different application areas, being approximately 274 worldwide in February 2016 [13]. Some examples are Abaxis (diagnostics), Advanced Liquid Logic (research instruments), Biosite (diagnostics), Chiral Photonics (packaging, prototyping, and manufacturing), Aixtek (consulting), FlowJEM (prototyping), Microfluidic Imaging (imaging), Cepheid (diagnostics), Cytonome (therapeutics), Micronics (custom development, manufacturing, and research instruments), Microflow Laboratory (consulting and prototyping), Medtronic (medical devices), Luna Innovations (contract R&D), ALine Inc. (development and components), and i-STAT (diagnostics). This technological boom led MIT Technology Review to nominate microfluidics as one of the 10 technologies that will change the world, with particular relevance in the life science area [14].

The present chapter provides a general description of the essential components and properties of LOC systems, including concepts of materials and fabrication techniques. Further, their applications in relevant biotechnological fields are presented and discussed. In particular, the applicability and advantages of microfluidic technologies in the pharmacological area will be highlighted. The main objective is to provide an overview to scientists and engineers on the possibilities and potential offered by microfluidic technologies to develop innovative and improved products for drug discovery and development.

2 Definition, Main Concepts and Characteristics

As briefly described above, LOC systems are based on a broader technology called microfluidics, the science and engineering of manipulating and processing small volumes of ...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Contributors
• Preface
• Section 1: Principle of Microfluidics
• Section 2: Microfluidics for Drug Delivery Applications
• Section 3: Microfluidics for Analysis and Drug Delivery
• Section 4: Future Prospective and Commercialization of Microfluidic Techniques
• Index