Sensitive optical biosensors for unlabeled targets: a review.

Polymers have assumed the leading role as substrate materials for microfluidic devices in recent years. They offer a broad range of material parameters as well as material and surface chemical properties which enable microscopic design features that cannot be realised by any other class of materials. A similar range of fabrication technologies exist to generate microfluidic devices from these materials. This review will introduce the currently relevant microfabrication technologies such as replication methods like hot embossing, injection molding, microthermoforming and casting as well as photodefining methods like lithography and laser ablation for microfluidic systems and discuss academic and industrial considerations for their use. A section on back-end processing completes the overview.

Polymer microfabrication technologies for microfluidic systems

Towards integrated and sensitive surface plasmon resonance biosensors: a review of recent progress.

Microfluidics is an emerging field that has given rise to a large number of scientific and technological developments over the last few years. This review reports on the use of various materials, such as silicon, glass and polymers, and their related technologies for the manufacturing of simple microchannels and complex systems. It also presents the main application fields concerned with the different technologies and the most significant results reported by academic and industrial teams. Finally, it demonstrates the advantage of developing approaches for associating polymer technologies for manufacturing of fluidic elements with integration of active or sensitive elements, particularly silicon devices.

https://iopscience.iop.org/article/10.1088/0960-1317/17/5/R01/pdf

Lab-on-chip technologies: making a microfluidic network and coupling it into a complete microsystem : a review

The application of portable, easy-to-use and highly sensitive lab-on-a-chip biosensing devices for real-time diagnosis could offer significant advantages over current analytical methods. Integrated optics-based biosensors have become the most suitable technology for lab-on-chip integration due to their ability for miniaturization, their extreme sensitivity, robustness, reliability, and their potential for multiplexing and mass production at low cost. This review provides an extended overview of the state-of-the-art in integrated photonic biosensors technology including interferometers, grating couplers, microring resonators, photonic crystals and other novel nanophotonic transducers. Particular emphasis has been placed on describing their real biosensing applications and wherever possible a comparison of the sensing performances between each type of device is included. The way towards achieving operative lab-on-a-chip platform incorporating the photonic biosensors is also reviewed. Concluding remarks regarding the future prospects and potential impact of this technology are also provided.

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Integrated optical devices for lab-on-a-chip biosensing applications

This paper describes a novel fabrication method for the manufacture of three-dimensional (3D) interconnected microchannels. The fabrication is based on a full wafer polymer bonding process, using SU-8 polymer epoxy photoresist as a structural material. The technology development includes an improvement of the SU-8 photolithography process in order to produce high uniformity films with good adhesive properties. Hence, 3D embedded microchannels are fabricated by a low temperature adhesive bonding of the SU-8 photopatterned thick films. The bonding occurs at temperatures (100–120 °C) lower than those usually applied in bonding technology. The bonding process parameters have been chosen in order to achieve a strong and void-free bond. High bond strengths, up to 8 MPa, have been obtained. Several examples using this new technology are shown, including bonding between different combinations of silicon and Pyrex wafers. This method also allows us to bond wafers with previously surface micromachined structures. Interconnected microchannels with vertical smooth walls and aspect ratios up to five have been obtained. Channels from 40 to 60 µm depth and from 10 to 250 µm width have been achieved. Liquid has been introduced at different levels into the microchannels, verifying good sealing of the 3D interconnected microchannels. The fabrication procedure described in this paper is fast, reproducible, CMOS compatible and easily implementable using standard photolithography and bonding equipment.

https://iopscience.iop.org/article/10.1088/0960-1317/14/7/027/pdf

Novel three-dimensional embedded SU-8 microchannels fabricated using a low temperature full wafer adhesive bonding

We present highly sensitive optical biosensors able to be fully integrated in lab-on-a-chip microsystems using standard CMOS compatible processes. These optical biosensors are based on integrated Mach–Zehnder interferometers, which have been designed to have high surface sensitivity and monomode behaviour. As a biosensing application of the devices we show the real-time detection of the covalent immobilization and hybridization of DNA strands without labelling. In order to achieve a lab-on-a-chip portable microsystem, we present the integration of the sensor with a CMOS compatible microfluidic system using SU-8 photolithography patterned layers.

https://iopscience.iop.org/article/10.1088/1464-4258/8/7/S41/pdf

Optical biosensor microsystems based on the integration of highly sensitive Mach–Zehnder interferometer devices

The fabrication, characterization and packaging of novel microfluidic-optical integrated biosensors for label-free biochemical detection is presented in this paper. The integrated device consists of a three-dimensional embedded microchannel network fabricated using enhanced CMOS compatible SU-8 multilevel polymer technology on top of a wafer containing Mach-Zehnder Interferometer (MZI) nanophotonic biosensor devices. PMMA housing provides connection to the macro-world and ensures robust leakage-free flow operation of the devices. This macro-microfluidic module can operate at pressure drops up to 1000 kPa. Fluid flow experiments have been performed in order to demonstrate the robustness of our microfluidic devices. The devices have been designed to operate under continuous flow. Steady-state flow rates ranging from 1 to 100 µl min−1 at pressure drops ranging from 10 to 500 kPa were measured in the laminar flow regime. Experimental results are in good agreement with laminar flow theory. The first interferometric sensing measurements are presented in order to demonstrate the functionality of these novel integrated devices for lab-on-a-chip and label-free biosensing applications. A bulk refractive index detection limit of 3.8 × 10−6 was obtained, close to the minimum detected up to now by label-free biosensor devices without microfluidic integration. As far as we know, this is the first time that a label-free biosensor device is integrated within a microfluidic network using a wafer-level CMOS compatible process technology.

https://iopscience.iop.org/article/10.1088/0960-1317/16/5/018/pdf

Microfluidic-optical integrated CMOS compatible devices for label-free biochemical sensing

This paper shows a novel use of SU-8, a photodefinable epoxy, to monolithically integrate low cost optical sensors and microfluidic structures. The chip consists of optical connectors, multimode waveguides and sealed microfluidic channels patterned in SU8 on a silicon substrate. We describe in detail an SU-8 microfabrication process consisting of (i) four successive photolithographic steps, (ii) a bonding process and (iii) a final releasing step. The core of the waveguide is made of standard SU-8, whereas its cladding, with a lower refractive index, is achieved by diluting the SU-8 in a liquid aliphatic resin. Despite the dilution, the SU-8/aliphatic mixture is still patternable by photolithography allowing us to fabricate microchannels. The input and output optical fibres are horizontally aligned to the waveguides by their insertion in U-Grooves, and vertically aligned by the elevation of the waveguide using a lower cladding layer that allows us to lift it up to meet the centre of a standard optical fibre. Microfluidic channels with smooth vertical walls (125 μm height and 30 μm width) have been achieved. Microchannels are sealed by low temperature adhesive bonding of the SU-8 photopatterned thick-films at a wafer level. Liquid flows in the channels verify good sealing of the microchannels. In order to validate the interaction of these optical-fluidic microcomponents, we carried out an absorption chemical assay. The fabrication procedure described in this article is a fast, reproducible, CMOS compatible and simple way to develop optical Lab-on-a-Chip devices using standard photolithography and bonding equipment.

A new SU-8 process to integrate buried waveguides and sealed microchannels for a Lab-on-a-Chip

The application of cantilevered structures as check valves or flow sensors can provide new possibilities towards the integration of accurate sample preparation systems within a lab-on-a-chip. The cantilevers presented in this paper act as flaps enclosed within a channel in a direction perpendicular to the flow. This orientation allows simpler designs and easier integration of the valve or flow sensor within the microfluidic network. The cantilevers have been embedded in a microfluidic channel by low temperature full wafer adhesive bonding. In this way, electrodes, microchannels, microchambers and cantilevers can be fabricated and sealed at the same time at a wafer level. To the author's knowledge, this is the first example of flap cantilevers embedded in a polymeric microfluidic channel. The mobility of the structure and the leakage are dependent on the size of the sealing gaps between the cantilever and the enclosing channel. In this paper, we present three different fabrication methods for a range of bottom sealing gaps from the micro to the nanometer size. The top sealing gap is determined by the adhesive bonding and is 11 µm wide. Furthermore, various geometrical features have been introduced in order to optimize a valve or flow sensor. The characterization of the structures comprises measurements of the sensitivity of each cantilever design by obtaining their relative spring constant, measurements of their elastic and plastic working regimes and Young's modulus of the SU-8.

http://iopscience.iop.org/article/10.1088/0960-1317/17/11/013/pdf

K Mayora

Papers

Novel three-dimensional embedded SU-8 microchannels fabricated using a low temperature full wafer adhesive bonding

Optical biosensor microsystems based on the integration of highly sensitive Mach–Zehnder interferometer devices

Microfluidic-optical integrated CMOS compatible devices for label-free biochemical sensing

A new SU-8 process to integrate buried waveguides and sealed microchannels for a Lab-on-a-Chip

Fabrication of SU-8 free-standing structures embedded in microchannels for microfluidic control