Unconventional LowCost Fabrication and Patterning

Authors: Himanshu Sharma Diep Nguyen Aaron Chen Valerie Lew Michelle Khine

Publish Date: 2010/12/09

Volume: 39, Issue: 4, Pages: 1313-1327

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Abstract

The potential of rapid quantitative and sensitive diagnosis has led to many innovative ‘lab on chip’ technologies for point of care diagnostic applications Because these chips must be designed within strict cost constraints to be widely deployable recent research in this area has produced extremely novel nonconventional micro and nanofabrication innovations These advances can be leveraged for other biological assays as well including for custom assay development and academic prototyping The technologies reviewed here leverage extremely lowcost substrates and easily adoptable ways to pattern both structural and biological materials at high resolution in unprecedented ways These new approaches offer the promise of more rapid prototyping with less investment in capital equipment as well as greater flexibility in design Though still in their infancy these technologies hold potential to improve upon the resolution sensitivity flexibility and costsavings over more traditional approachesAt the interface between fundamental academic research and the global demand for lowcost translational biomedical technology lays an exciting bridge that has led to many recent significant advances in point of care POC diagnostics4693 Since the 1970s the development of POC technologies can be seen in such devices as glucose and urine sensors which have been miniaturized and adopted for household use28 In short these tests can be administered at a patient’s locale and even by the patient himself offering not only convenience but significantly more rapid diagnosis than conventional labbased testing Reducing the time to diagnosis from days to minutes enables better patient management decisions that may lead to improved patient compliance prognosis and reduced overall cost of careWithin this past decade lab on chip LOC growth has been driven by its numerous advantages over macroscale devices including faster reaction time less reagent and sample consumption portability and lower capital equipment costs417677388 Advantages gained from microfabrication and nanofabrication approaches have since been leveraged for chemical biological and physical processes from the molecular to the cellular scales Applications of such microfluidicbased LOC devices include fractionation mixing purification reactions separations and detections923 These technologies have the potential to simplify and improve the efficacy of analytical assays by negating the need for dedicated laboratories complex equipment highly trained personnel and expensive labbased infrastructure These approaches have been applied to a variety of fields from drug discovery for improved molecular assays to biomimetic devices for tissue engineering1226In particular the potential of rapid quantitative and sensitive diagnosis has led to many innovative LOC technologies for POC applications Perhaps the most compelling application of LOC technologies for POC is in the early and accurate detection of infectious agents in developing countries where resources are severely limited79 To be adopted for use in developing countries the technologies must be extremely inexpensive robust scalable easily adaptable to detecting various infectious agents sturdy to use under harsh and resource limited environments and simple to useBecause POC applications are so cost sensitive total burdened cost for disposable devices need to be below 5 in the developed country and close to pennies in developing countries effective technologies that can be developed with this constraint hold much potential to be leveraged for other applications as well especially for custom assay development and academic prototyping2093 The main goal of this review is to therefore provide the reader with a survey of novel fabrication techniques as alternatives to more conventional expensive and time intensive traditional approaches These new approaches offer the promise of more rapid prototyping with less investment in capital equipment as well as greater flexibility in design Though many of these technologies are still in their infancy they hold potential to improve upon the resolution sensitivity flexibility and costsavings over more traditional approaches Here we focus our review on promising lowcost fabrication techniques for POC applications We seek to find inspiration here from researchers focused on POC applications that have developed novel lowcost fabrication technologies that obviate many of the legacy micro and nanofabrication processes largely inherited from the semiconductor industry We start with a brief review of the traditional fabrication processes Then describe how POC researchers have developed ways to leverage extremely lowcost substrates and then pattern both structural and biological materials at high resolution in unprecedented ways The structural material can be patterned for microfluidic channels or for integrated nanostructures for enhanced assay sensitivity Novel approaches to pattern biological materials are then reviewedThe ability to pattern structural and biological materials at high resolution offers unprecedented sensitivity and insight enabling many recent biomedical investigations2133347186 Traditional ‘top down’ silicon and glass microfabrication techniques—including photolithography thin film deposition etching and bonding—have been leveraged to create complex LOC for applications from immunoassays to PCR reactions to single cell analysis101447505156889197 However largely inherited from the semiconductor industry these fabrication processes are inherently limited in resolution and planarity by the tooling sourcesIn photolithography patterns are created by UV irradiation of photosensitive polymers for selective crosslinking thus generating the desired topography72 Film deposition involves the formation of thin films on the surface of a substrate and have been used for a variety of purposes in microstructure fabrication85 This has been accomplished by utilizing various chemically and physically driven processes such as chemical vapor deposition plating chemical solution deposition physical vapor deposition and molecular beam epitaxy1125445785 Etching is used to selectively remove or create features on materials and has been accomplished by using physical or chemical methods9 Etching has been performed using either wet methods such as liquid chemicals or dry etching such as gasphase chemistry4485 Bonding is a method to adhere substrates together to form a hermetic seal9 Depending on the material of interest different forms of bonding can be applied such as anodic fusion thermocompression or adhesive bonding to obtain desired structures985 Most of these processes require legacy capital equipment from the semiconductor industry typically housed in a cleanroom that is extremely costly to run

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