T.
Wienhold
*a,
S.
Kraemmer
b,
S. F.
Wondimu
a,
T.
Siegle
b,
U.
Bog
ac,
U.
Weinzierl
d,
S.
Schmidt
d,
H.
Becker
d,
H.
Kalt
b,
T.
Mappes
ae,
S.
Koeber
af and
C.
Koos
*af
aInstitute of Microstructure Technology (IMT), Karlsruhe Institute of Technology (KIT), 76128, Karlsruhe, Germany. E-mail: tobias.wienhold@kit.edu; christian.koos@kit.edu
bInstitute of Applied Physics (APH), Karlsruhe Institute of Technology, 76128 Karlsruhe, Germany
cNow with Institute of Nanotechnology (INT), Karlsruhe Institute of Technology, 76128 Karlsruhe, Germany
dMicrofluidic ChipShop GmbH, 07747 Jena, Germany
eNow with Carl Zeiss AG, Corporate Research and Technology, 07745 Jena, Germany
fInstitute of Photonics and Quantum Electronics (IPQ), Karlsruhe Institute of Technology, 76128 Karlsruhe, Germany Web: http://www.ipq.kit.edu
First published on 12th August 2015
We present an all-polymer photonic sensing platform based on whispering-gallery mode microgoblet lasers integrated into a microfluidic chip. The chip is entirely made from polymers, enabling the use of the devices as low-cost disposables. The microgoblet cavities feature quality factors exceeding 105 and are fabricated from poly(methyl methacrylate) (PMMA) using spin-coating, mask-based optical lithography, wet chemical etching, and thermal reflow. In contrast to silica-based microtoroid resonators, this approach replaces technically demanding vacuum-based dry etching and serial laser-based reflow techniques by solution-based processing and parallel thermal reflow. This enables scaling to large-area substrates, and hence significantly reduces device costs. Moreover, the resonators can be fabricated on arbitrary substrate materials, e.g., on transparent and flexible polymer foils. Doping the microgoblets with the organic dye pyrromethene 597 transforms the passive resonators into lasers. Devices have lasing thresholds below 0.6 nJ per pulse and can be efficiently pumped via free-space optics using a compact and low-cost green laser diode. We demonstrate that arrays of microgoblet lasers can be readily integrated into a state-of-the-art microfluidic chip replicated via injection moulding. In a proof-of-principle experiment, we show the viability of the lab-on-a-chip via refractometric sensing, demonstrating a bulk refractive index sensitivity (BRIS) of 10.56 nm per refractive index unit.
One fundamental restriction of using high-Q on-chip resonators in a disposable LoC arises from the limitation to silicon wafers as substrate material. Resonators are commonly fabricated from thin silica or polymer layers on the silicon wafer surface.10,11,19,20 In order to confine light within the cavity, the high-index silicon substrate underneath the patterned resonators must be removed by selective isotropic underetching. This is most commonly done using highly corrosive and toxic xenon difluoride (XeF2) gas as an etchant.21 The associated vacuum-based dry etching process is technically demanding and requires multiple alternating etching and evacuation cycles, thereby limiting the throughput of this process and hindering large scale fabrication. For conventional silica-based microtoroid fabrication, throughput is additionally limited by the serial CO2-laser reflow required to reduce fabrication induced defects along the cavity surface.
Another fundamental restriction of WGM resonators without optically active components is device probing and read-out, which is typically realized via phase-matched evanescent coupling.22 For planar microcavities, e.g. microrings, evanescent coupling can be realized via access waveguides. However, this concept cannot be used for devices elevated on a pedestal, which have shown significantly higher quality factors than planar integrated ring resonators. Instead, evanescent coupling is commonly realized using a tapered optical fibre, which requires relative positioning of the fibre taper and the resonator with sub-micrometre precision.22 The elaborate taper fabrication and the need for vibration control limit device operation to a controlled laboratory environment and prevent deployment in point-of-care diagnosis. Moreover, evanescent coupling with a fibre taper cannot be applied to extended resonator arrays, hindering application in multiplexed sensing systems, and the fibre tapers complicate device integration into microfluidic systems. To overcome these issues, monolithic integration of microtoroid resonators and access waveguides has been demonstrated,23 but this approach requires a complex fabrication sequence. Furthermore, device operation has so far only been demonstrated at near-infrared wavelengths, limiting the applicability for sensing in aqueous media due to increased absorption of water at these wavelengths.
In this article, we introduce a novel concept of WGM biosensors that can be fabricated in large arrays on arbitrary substrates using cost-efficient solution-based processing. The sensors consist of WGM resonators in the shape of microgoblets10 and can be fabricated using highly scalable parallel processing. The microgoblets are supported on pedestals formed from a polymer layer added between substrate and resonators, which can be structured using wet chemical processing. The devices are doped with a laser dye and can be optically pumped and probed via free-space optics. We show efficient excitation of the microgoblet lasers with a compact and low-cost green laser diode. In a proof-of-principle experiment we integrate an array of 100 microgoblet lasers into a microfluidic chip and demonstrate the viability of the LoC system via refractometric sensing.
To allow using the WGM sensor chips as disposables, we introduce a novel fabrication process that enables fabrication of microgoblet laser arrays from polymers using solely parallel fabrication processes. Instead of producing the resonator pedestals by etching of the carrier substrate, an additional thin polymer film is inserted between substrate and resonator layer. Pedestals supporting the WGM cavity can be formed from etching this intermediate layer rather than by selectively removing the substrate itself. This process enables resonator fabrication on arbitrary substrate materials, including transparent or flexible polymer films. A scanning electron micrograph of an all-polymer microgoblet laser is depicted in Fig. 1a. The device consists of a goblet-shaped cavity made of poly(methyl methacrylate) (PMMA), which is supported on a polymer pedestal. Instead of conventional vacuum-based gas-phase processing using, e.g., XeF2 as an isotropic etchant for the silicon substrate, our fabrication concept is based on wet chemical processing of polymers, which enables easy upscaling of substrate sizes and fabrication throughput. A resonator array fabricated by parallel solution-based processing is depicted in Fig. 1b. The combination of low-cost materials and full scalability of all fabrication steps significantly reduces the sample costs and enables use of the microgoblet resonators in disposable sensing chips. For on-chip sensing applications, resonator arrays can be integrated into state-of-the-art microfluidic chips, forming a compact photonic LoC (Fig. 1c).
Fig. 1 PMMA microgoblet lasers fabricated on a polysulfone substrate: (a) zoom-in of a single PMMA microgoblet laser supported on a polymer pedestal made from lift-off resist. (b) Array of 100 microgoblet lasers fabricated by parallel solution-based processing. (c) Photograph of a sensing chip: an array of 100 microgoblet lasers identical to Fig. 1b is integrated into a microfluidic chip. Transparency of the chip enables optical addressing of individual microgoblets through the lid via free-space optics. |
To minimize the costs and size of the optical pump unit, a laser diode is used for excitation. Pumping of WGM lasers with laser diodes has so far only been demonstrated using organic semiconductor thin-films as gain medium.26 However, due to photo-oxidation of the gain medium, these lasers could only be operated in a vacuum chamber, preventing actual sensing applications in a LoC. Here, we instead use the organic dye pyrromethene 597 (PM597) as gain material, which has been demonstrated as an efficient light emitter in various types of microlasers.27,28 The superior photostability of PM597 enables stable laser operation under common ambient conditions. The dye's absorption maximum lies in the green spectral range, while its emission occurs at orange-red wavelengths. Until recent years, laser diodes with direct emission in the green spectral range were not commercially available and pumping at these wavelengths could only be achieved with frequency-doubled solid-state lasers. Recent progress in the GaN-based laser diode fabrication has enabled devices with direct green emission. In our experiment, the beam of a green laser diode is loosely focussed onto the cavity and emission from the microgoblet laser is collected with a microscope objective from the top of the sample. Spectral analysis is performed with a Czerny–Turner spectrometer.
Suitable substrate materials have to provide a high heat deflection temperature to maintain mechanical stability during the reflow process. The polymer polysulfone (PSU) is well suited for this purpose due to its high glass transition temperature of 190 °C, which is well above the reflow temperature used to anneal the PMMA resonators. PSU was purchased as 380 μm thick foils (LITE U, LITE GmbH) and further flattened via hot embossing between two silicon wafers to reduce its surface roughness. Flattened foils are approx. 350 μm thick and can easily be cut using a wafer dicing saw or common paper scissors.
The sacrificial layer between resonator and substrate has to allow for selective and isotropic etching without damaging the PMMA resonators or polymer substrates. Additionally, this material has to provide thermal stability during resonator reflow. Polydimethyl glutarimide-based lift-off resist (LOR) (LOR 30B, Microchem Corp.) provides all required properties as intermediate layer and allows selective wet chemical etching without dissolving the PMMA or the substrate.
A detailed schematic of the fabrication sequence is depicted in Fig. 2a–e. First, a five micrometre thick layer of LOR 30B is spin-coated onto the polymer foils as a spacer and subsequently baked on a hot plate for thermal annealing and to prevent pedestal deformation during resonator reflow. Resonators are structured from PMMA photoresist (PMMA 950k, MicroChem Corp.) mixed with the laser dye PM597 (Radiant Dyes Laser & Accessories GmbH) at a concentration of 2.56 × 10−5 mol g−1. The resist mixture is spin-coated onto the LOR layer and baked to remove residual solvent. PMMA disks with 50 μm diameter are structured via deep-UV lithography using a mask aligner (EVG 620, EV group). A 5′′ photomask containing multiple resonator arrays of 10 by 10 resonators was used for all exposures. In one single exposure, multiple resonator arrays on an area as large as a 4′′ wafer could be structured simultaneously. Exposed PMMA is subsequently developed in a 1:1 mixture of methyl isobutyl ketone (MIBK) and isopropyl alcohol (IPA). Samples are immersed in a tetra-ethyl-ammonium-hydroxide-(TEAH)-based developer (101A Developer, Microchem Corp.) to underetch the PMMA disks isotropically. Etching is stopped at a pedestal diameter of approx. 25 μm, leaving the rim of the disks freestanding. To reduce fabrication-induced defects along the resonator rim, a thermal reflow is performed. Samples are heated on a hot plate to 130–135 °C under ambient atmosphere. At this temperature, softening of the PMMA allows thermal reflow of the disks due to the release of surface free energy. This induces the formation of the characteristic microgoblet shape. Finally, individual resonator arrays can be cut from the substrate using scissors. Integration of microgoblet laser arrays into microfluidic chips as depicted in Fig. 2f–h is described in detail below.
Quality factor | |
---|---|
Electron beam lithography (silicon substrate) | 1.5 × 105 |
Deep-UV lithography (silicon substrate) | 2.5 × 105 |
Deep-UV lithography (polysulfone substrate) | 1.4 × 105 |
The quality factors of resonators structured by electron beam lithography and deep-UV lithography lie within the same order of magnitude. Furthermore, the quality factors of resonators fabricated on silicon and polysulfone substrates fall within the same range. Hence, the achievable quality factors are independent from the lithography technique and the substrate material.
To determine the lasing thresholds, emission spectra of the microgoblet lasers were recorded for increasing pump pulse energies. For each spectrum, the area under the investigated lasing peak was accumulated and plotted over the corresponding pump pulse energy. Linear fits were applied to the data points below and above the characteristic kink in the plot and the lasing threshold was determined by intersecting both lines. Fig. 3 shows an input–output curve of a microgoblet lasers structured by deep-UV lithography on a PSU substrate. The device has a lasing threshold of 0.54 nJ per pulse. Independent of the substrate material or the lithography technique used for device fabrication, lasing thresholds were typically below 1 nJ per pulse. Immersion of the devices in water resulted in an increase of the lasing threshold, which can be attributed to higher radiation loss in the cavity due to the decreased refractive index contrast. Still, lasing thresholds of immersed cavities typically stayed well below 3 nJ per pulse. Considering the maximum pulse energy emitted by the laser diode of 95 nJ, stable operation of the microgoblet lasers even significantly above their lasing threshold was possible.
A schematic of the fabrication sequence for microfluidic chips is depicted in Fig. 2f–h. Microfluidic chips were replicated from PMMA via injection moulding. Subsequently, depressions with a depth of 400 μm were milled into the fluidic channels to support the resonator chips. The resonator substrates supporting an array of 100 microgoblet lasers were fixed inside these depressions using UV curing acrylated urethane medical adhesive. Finally, the microfluidic chips were sealed with a planar polymer lid. High transparency of the fluidic chips enables optical pumping and read-out of the microgoblet lasers through the lid. The fluidic periphery was connected to the microfluidic channels via mini Luer slips on the chip. A photograph of a microfluidic chip with an integrated microgoblet laser array is depicted in Fig. 1c.
To the best of our knowledge, this is the first fully encapsulated lab-on-a-chip based on WGM resonators which are solely made from polymers and fabricated using parallel largely scalable fabrication processes. We believe that this concept will enable using the chips as low-cost disposables in a photonic sensing platform for point-of-care diagnostics. Handling and operation of our chips is significantly facilitated as no evanescent fibre coupling is required. Excitation and read-out of the resonators is solely achieved via free-space optics and hence allows for easy sample alignment.
In future work, the sensing chips may further be enhanced by integrating microoptical structures onto the polymer chip. Specifically, the read-out efficiency may be significantly increased by directing the microgoblet laser emission to the spectrometer using conical micromirrors.30 For specific sensing of multiple reagents, the surface of different resonators of the array may be functionalized via polymer-pen lithography (PPL) prior to on-chip integration.34 Multiplexed read-out of multiple microgoblet lasers may be used for referenced sensing or parallel label-free detection of different markers,35 which may allow, e.g., rapid screening in food safety assurance or identification of complex diseases. To enhance the portability of the read-out system, spectral analysis may be performed with a miniaturized spectrometer.36
This journal is © The Royal Society of Chemistry 2015 |