Abstract
Since the early 2000s, extensive research has been performed to address numerous challenges in biochip and biosensor fabrication in order to use them for various biomedical applications. These biochips and biosensor devices either integrate biological elements (e.g., DNA, proteins or cells) in the fabrication processes or experience post fabrication of biofunctionalization for different downstream applications, including sensing, diagnostics, drug screening, and therapy. Scalable lithographic techniques that are well established in the semiconductor industry are now being harnessed for large-scale production of such devices, with additional development to meet the demand of precise deposition of various biological elements on device substrates with retained biological activities and precisely specified topography. In this review, the lithographic methods that are capable of large-scale and mass fabrication of biochips and biosensors will be discussed. In particular, those allowing patterning of large areas from 10 cm2 to m2, maintaining cost effectiveness, high throughput (>100 cm2 h–1), high resolution (from micrometer down to nanometer scale), accuracy, and reproducibility. This review will compare various fabrication technologies and comment on their resolution limit and throughput, and how they can be related to the device performance, including sensitivity, detection limit, reproducibility, and robustness.
Highlights
Since the early 2000s, extensive research has been performed to address numerous challenges in biochip and biosensor fabrication in order to use them for various biomedical applications
This review aims to discuss the production of biochips and biosensors through micro- and nanolithographic methods that are capable of arbitrary patterning, are scalable to large areas,[28,29,35] and are applicable for “soft” biological molecules or biologically compatible materials
The increasing interaction between device fabrication, chemistry, and biotechnology communities is leading to an increasing number of processes that can be used in large-scale biochip and biosensor fabrication, which will be necessary for the practical deployment of such devices in “real world” applications
Summary
The increasing interaction between device fabrication, chemistry, and biotechnology communities is leading to an increasing number of processes that can be used in large-scale biochip and biosensor fabrication, which will be necessary for the practical deployment of such devices in “real world” applications. The examples discussed which only employ one lithographic method, address only some of these idealized characteristics in the final biochip or biosensor (e.g., in resolution, throughput, compatibility with the biomolecule of interest) In the future, this might be overcome by further improvements in lithographic approaches and a better synergy between lithography, printing technologies (e.g., inkjet and screen printing, as well as 3D printing),[37] and molecular selfassembly.[34,183] emerging methods such as multiplexed scanning probe lithography may in future be viable at the manufacturing scale.[184−186] this type of lithography has already been demonstrated at the 3 in.
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