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Frontiers in Lab on a Chip Technologies ·

Volume 3 - 2024 | https://doi.org/10.3389/frlct.2024.1412290

Categorising hybrid material microfluidic devices

  • Tom Carvell1
  • Paul Burgoyne2
  • Alasdair R. Fraser2
  • Helen Bridle1*corresponding author
  1. 11 Institute of Biological Chemistry, Biophysics and Bioengineering, School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh, United Kingdom
  2. 22 Tissues, Cells and Advanced Therapeutics, Jack Copland Centre, Scottish National Blood Transfusion Service, Edinburgh, United Kingdom
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Abstract

Microfluidic devices are useful tools for a wide range of biomedical, industrial, and environmental applications. Hybrid microfluidic devices utilising more than two materials are increasingly being used for their capacity to produce unique structures and perform novel functions. However, an analysis of publications across the field shows that whilst hybrid microfluidic devices have been reported, there remains no system of classifying hybrid devices which could help future researchers in optimising material selection. To resolve this issue, we propose a system of classifying hybrid microfluidic devices primarily as containing either hybrid structural, chemical, or electrical components. This is expanded upon and developed into a hierarchy, with combinations of different primary components categorised into secondary or tertiary hybrid device groupings. This classification approach is useful as it describes materials that can be combined to create novel hybrid microfluidic devices.

Keywords

Introduction

The term microfluidics describes the manipulation of tiny volumes of fluid within channels at the microscale (Akbari et al., 2023). Prior to the advent of microfluidics as a defined field, micro-sized channels were often contained within components of scientific and engineering instruments mostly unrelated to microfluidic applications (Ren et al., 2013; Convery and Gadegaard, 2019). Currently when compared with early microfluidics, microchannels with various geometries are used for many different applications and have huge potential for use within biomedical science (Ramachandraiah et al., 2017; David et al., 2019; Lu et al., 2019; Pritchard et al., 2019; Guzniczak et al., 2020; Xie et al., 2022), industrial processing (Estrada-Osorio et al., 2024; Jayan et al., 2024; Wang et al., 2024; Yi et al., 2024), environmental research (Hill et al., 2022; AlMashrea et al., 2024; Du and Yang, 2024; Sun et al., 2024) and increasingly reaching into other fields (Apoorva et al., 2024; Lei et al., 2024; Reyes et al., 2024). The manufacturing of these microchannels relies upon the use of appropriate techniques, equipment, and materials to produce microfluidic devices consistently and accurately (Ren et al., 2013; Gale et al., 2018; Scott and Ali, 2021; Akbari et al., 2023). New applications often require new channel geometries and the integration of novel components, and it is therefore not unreasonable to suggest that new manufacturing techniques and materials will be necessary to facilitate new microfluidic applications. Hybrid microfluidic devices, comprised of more than one type of material, can be used to meet these requirements. As part of the evaluation of the current state of microfluidic device manufacturing, this mini review focuses on hybrid microfluidic devices that utilise a combination of fabrication techniques and are comprised of at least two materials. Hybrid devices have been reviewed elsewhere but the reviews focus on a summary of the concepts of combining materials (Ren et al., 2013) or require substantial updating in line with current findings (Hou et al., 2017).

Materials and methods

This review expands upon two previous publications (Ren et al., 2013; Hou et al., 2017) that simply described material considerations for use in hybrid microfluidic devices, and for the first time provides a system of categorization of hybrid microfluidic devices. Between February and March 2024, literature searches of PubMed were performed using the following terms: “Hybrid microfluidic device,” “PDMS hybrid device,” “Composite microfluidic device,” “Glass hybrid device,” “PMMA hybrid device,” and “Polymer hybrid device” with a focus on relevant literature published since 2013.

Although this review aims to provide an update to previous hybrid device reviews, it is not an exhaustive list; examples of devices were chosen to demonstrate both the diversity in material choice and flexibility with which they can be combined for different applications. This was considered of particular importance as it is known that material selection impacts flow, biocompatibility and function of microfluidic devices (Nielsen et al., 2020). A range of papers with different applications were therefore included, and this review will aid researchers in material choice for future microfluidic device designs. The materials related to tubing and fluid connections were considered outside the scope of this review.

Outcomes

Hybrid microfluidic devices have previously been described in a variety of ways and do not have sub-categories to define related device compositions. We propose categorising hybrid microfluidic devices into three primary categories; composites as electrical components; composites as chemical components and composites as structural components.

When considering primary categories, hybrid devices can contain electrical components (comprehensively reviewed in (Tawade and Mastrangeli, 2024)) that are integrated and used as sensors or for performing functions such as organ-on-chip monitoring, or cell-matrix interactions within the microfluidic channel. Second, chemical components are integrated into hybrid devices in the form of surface coating materials (reviewed in (Tu et al., 2012)), or as catalysts (reviewed in (Solsona et al., 2019)) for chemical reactions and others. The third category is hybrid devices using composite materials as structural components. Here, two different materials are bonded together to form the walls of the microchannel or as one material acting as a filter within the microchannel, as well as for less functional reasons, such as one material simply acting as a support substrate. When the microfluidic device has a single function, they can be referred to as a primary hybrid device, but different combinations are possible and secondary (containing two types of hybrid components), and tertiary (containing all three types of hybrid components) are also possible to fabricate. This is presented schematically in Figure 1 where examples of microfluidic structures are depicted for each category. In the structural component bubble, an inertial focusing channel is shown and has been fabricated with two materials shown in yellow and red. The chemical components bubble shows a microchannel structure (red) with a functional coating (yellow) whereas the electrical component bubble depicts a microfluidic device with an integrated component (black circuit).

Categorisation of hybrid microfluidic devices. The three primary categories of chemical (surface coating in yellow, microchannel in red), structural (materials shown in yellow and red) and electrical (electrodes in black) can be combined to form secondary or tertiary categories of device.
Figure 1. Categorisation of hybrid microfluidic devices. The three primary categories of chemical (surface coating in yellow, microchannel in red), structural (materials shown in yellow and red) and electrical (electrodes in black) can be combined to form secondary or tertiary categories of device.

At least two different materials need to be incorporated for a device to be categorised as a primary hybrid microfluidic device and must form the microchannel walls to be considered a primary structural device. Hybrid devices can be considered primary electrical component devices where an electrical component is integrated but the channel is comprised of only one material. A primary chemical component can be considered a hybrid device where the microchannel is coated with a chemical reagent or the device itself is comprised of a functionalised material to perform the intended application. For the purposes of this review, devices containing reservoirs or those that require the introduction of reagents to the fluidic system are not classified as part of the chemical component category. All other hybrid devices can be considered as devices characterised as having combinations of these primary components and are therefore defined as secondary or tertiary hybrid devices. An extensive, but not exhaustive, list of example hybrid devices across the hierarchy is presented in sections A, B and C of Table 1 with discussions of specific devices of interest.

TABLE 1. Categorisation of hybrid microfluidic devices.

Hybrid device sub-categoryMaterialComposited withManufacturing technique(s)Application(s)Exemplar reference
Section A: Primary hybrid devices
StructuralPhotosensitive resinAdhesive tapeDLP-3D printing and stackingDemonstrating shear stress chip and hydrogel microsphere generationQiu et al. (2023)
PDMSPMMA and adhesive tapePhotolithography and laser ablation‘Lab-on-a-chip’Hassanpour-Tamrin et al. (2021)
GlassStereolithography 3D-printing of moulds and castingDroplet microfluidics, fluid mixingVedhanayagam et al. (2023)
Replica moulding, solvent assisted bondingSolution exchange and interleukin-2 detectionPramanik and Suzuki (2019)
PMMA, adhesive tape and glassLaser ablation, stackingCell encapsulationEnck et al. (2020)
PDMS membraneSoft lithography and chemical etchingMechanically active organ-on-a-chipHuh et al. (2010)
Agarose/agarSoft lithography and hydrogel injectionComplex gradient of diffusible moleculesWu et al. (2006)
Hydrogel, glass, epoxy, and adhesive tapePhotopatterning and stackingMultifunctional microfluidic systemsBeebe et al. (2000)
Hydrogel and PMMASoft lithography, moulding, laser ablation3D cell cultureDo et al. (2023)
PolycarbonateSoft lithographyCell cultureChang et al. (2014)
Sol-gel method‘Lab-on-a-chip’Suzuki et al. (2010)
Polyvinylchloride
Polypropylene
PMMA
Soft-lithography, laser ablation and stackingProduction of monodisperse water-in-oil dropletsNakatani et al. (2020)
Various thermoplasticsCarbon–nitrogen covalent bondingContinuous flow polymerase chain reactionSivakumar et al. (2020)
poly (lactic-co-glycolic acid)Photolithography, moulding3D cell culture with a blood vessel architectureYuan et al. (2012)
PMMA and cotton3D printing, soft lithography, thermal bondingTumour-on-a-chipPalacio-Castañeda et al. (2020)
PMMASiliconLaser ablation‘Lab-on-a-chip’Capodacqua et al. (2023)
SiliconMicromilling, stackingMicrobioreactorsAbaci et al. (2012)
Polyethylene terephthalate membraneMicromilling, chemical bondingCytotoxicity of drug testingNguyen et al. (2019)
Polybutyl methacrylateLaser ablation, micromilling, thermal fusion bonding‘Lab-on-a-chip’Li et al. (2023)
Thermoplastic elastomers (various)Laser ablation, thermal diffusion bondingOrgan-on-a-chip/real-time live-cell analysisBusek et al. (2021)
Polycarbonate, polytetrafluoroethylene and aluminiumStackingEnrichment of exosomesHua et al. (2023)
Acrylate-based resin and adhesive tape3D-printing, stacking‘Lab-on-a-chip’Razavi Bazaz et al. (2020)
Polyimide filmLaser ablation, stacking‘Lab-on-a-chip’Thaweeskulchai and Schulte (2023)
Glass, photoresistDry film photoresist‘Lab-on-a-chip’Fan et al. (2018)
Adhesive tapeLaser ablation, micromilling‘Lab-on-a-chip’Ku et al. (2018)
SU-8Photolithographic techniques, laser ablationCell separation, medium exchangeCarvell et al. (2024)
Fluoroethylene propylenePolyimideLaser ablation, thermal bondingFluid mixingKim et al. (2016)
Wax and polyolefins-based filmsPMMA or PVC or glassLaser ablation, thermal bondingVarious biochemical applications, demonstration of bacterial cultivationWei et al. (2023)
GlassAdhesive tapeLaser ablation, micromilling‘Lab-on-a-chip’Ku et al. (2018)
Silicon, aluminium oxideAnodization of aluminium, deep reactive-ion etching, wet etching, clampingGas-permeable cultivation of HACaT-cellsBunge et al. (2018)
Polyurethane-methacrylatePolyurethane-methacrylate coated glassCasting, conformal coating, UV curation‘Lab-on-a-chip’Kuo et al. (2009)
Polyvinyl chlorideSiliconLaser ablation, jigsaw assemblySeparation of cellsZhu et al. (2021)
ChemicalPDMSHydrogelSoft lithographyCardiomyocyte cultureAnnabi et al. (2013)
Zinc oxide quantum dotsSoft lithographyTemperature-sensitive microfluidic deviceZhou et al. (2009)
Polycaprolactone-collagen membrane and cyclic olefin copolymerMicromilling, moulding, electrospinningLung-on-a-chipKanabekova et al. (2024)
GlassAcrylate-based photo-co-polymersStereolithographic ‘3P-printing’ using a ‘Print-Pause-Print protocol’Not author definedAhmadianyazdi et al. (2023)
ElectricalPMMAPlatinum electrodesMicromilling, hot-embossing, wire embeddingCell viability analysisEades et al. (2023)
SiliconGold nanoparticlesCombining extrusion printing and aerosol jet printingAmperometric sensing of lactate in sweatDu et al. (2024)
Section B: Secondary hybrid devices
Structural, electricalPDMSGlass, electrical componentsSoft lithography and sputteringAnalyte separation or serotonin detectionMoraes et al. (2012), Shameli et al. (2012)
Etching, sputtering, soft lithographyPolymerase chain reactionKaigala et al. (2008)
Anisotropic etching of an amorphous bulk materialVariousMu et al. (2009)
Various, but mostly the incorporation of electrodes in chip‘Lab-on-a-chip’Qiu et al. (2003), Li et al. (2008), Zhou et al. (2010)
CastingConcentration of analyteMatsui et al. (2007)
Photolithography, etching, stackingDNA sequencingBlazej et al. (2006)
Soft lithography, spin coating, aerosol printing of nanoparticles inside microfluidic structuresAuthors demonstrated bipolar electrode experiments; other applications possibleBroccoli et al. (2023)
Photolithography, sputtering, reactive ion etching, printed circuit boardCell-scale precise temperature controlLei et al. (2019)
Glass, polyimide, electrical componentsPhotolithography, spin coating, electrode patterningDroplet digital nucleic acid amplificationCoelho et al. (2023)
PMMA, glass, electrical componentsPhotolithography, hole punch, mechanical pressure assembly‘Lab-on-a-chip’Pérez-Sosa et al. (2022)
SU-8, electrical componentsPhotolithographyMicroparticle manipulationGuo et al. (2010)
Lactate monitoringWu et al. (2005)
Polycarbonate, electrical componentsSoft lithography‘Lab-on-a-chip’Kuo et al. (2003)
SU-8 and polycarbonateSoft lithography, moulding and hot embossingSingle cell and manipulationChartier et al. (2003)
SU-8 and quartzSpin-coating and soft-lithographyIsolectric focusing of proteinsOu et al. (2009)
Polyimide, graphene electrodesLaser ablation, stackingWearable devices, point-of-care diagnosticsThaweeskulchai and Schulte (2022)
Glass, silicon, polyimideStacking, printed circuit board technologyDetection of magnetically labelled proteinWu et al. (2010)
GlassSiliconPhotolithography and wet chemical etchingPolymerase chain reactionWang and Burns (2009)
Polycarbonate filmGlass fibres, Mediprene OF 400M, electrical componentsPhotolithography, micromachining, or injection mouldingExtraction of nucleic acids from bloodBrassard et al. (2019)
Structural, chemicalPDMSAgarCasting and layeringInvestigating the oviposition behaviour of DrosophilaLeung et al. (2015)
Soft lithographyInvestigating associative learning behaviour of C. elegansZhu et al. (2023)
Agar and glassReplica moulding and stackingSingle cell dynamic studiesWong et al. (2010)
Poly (lactic-co-glycolic) acid coated glassSoft lithography, electrospinningIn situ monitoring of stem cellsHesari et al. (2016)
Poly-2-hydroxy ethyl methacrylateMicromoulding, castingUsed to replicate a perfusion microfluidic-based cell culture deviceSantaniello et al. (2015)
Glass and hydrogelPhotolithography, gel castingHydrogel matrix degradability-dependent 3D cell invasion modelsTrappmann et al. (2017)
Device 1: Polycarbonate track-etched membraneSoft lithography, plasma treatment, electroplating, engraving, stackingIn vivo detection of small extracellular vesiclesCong et al. (2024)
Device 2: indium-oxide coated glass, nickel materials
Chromatography paperWax printing, PDMS castingDetection of Campylobacter jejuniChen et al. (2023)
PMMAPoly-2-hydroxy ethyl methacrylateMicromoulding, castingUsed to replicate a perfusion microfluidic-based cell culture deviceSantaniello et al. (2015)
PaperLaser ablation and clampingDetection of IgGSanjay et al. (2020)
Polyethylene terephthalate and paperLaser ablation and stackingDetection of cyclamateLiu et al. (2023)
Detection of potassium from whole bloodTseng et al. (2022)
Paper and glassLaser ablation, thermal bondingEnzyme-linked immunosorbent assayAbate et al. (2020)
Adhesive tape and polyethersulfone membraneLaser ablation, stackingCleaning of urea/‘Lab-on-a-chip’Gupta et al. (2023)
Polymer supportsCell-containing bioinks or hydrogels3D-printing3D cell culture modelsRichard et al. (2020)
Cell cultureKrakos et al. (2023)
SiliconPerfouoro copolymer and biomoleculesPhotolithography, reactive ion etching, biomolecule conjugationDetection of carcinoembryonic antigenWashburn et al. (2009)
GlassPolycaprolactoneOxygen radical exposure of masks composited with glass microfibres‘Lab-on-a-chip’, demonstrated colorimetric assay for protein quantificationBandara et al. (2018)
PDMS and enzyme-contained hydrogelHard and soft lithography, surface activation of glass, enzyme immobolisationMulti-enzymatic reactionsSimon et al. (2019)
PDMS and poloxamerPhotolithography, channel coatingDeterministic lateral displacement-dependent cell isolation from breastmilkHawkins et al. (2024)
Photocurable resinHydrogel, polystyrene, well platesMicromilling, 3D printingSegregated coculture of cellsBerry et al. (2017)
ClothPaper, metal-organic frameworks composited with molecularly imprinted polymersPrinting, ‘origami-folding process’, clampingColorimetric detection of gonyautoxinXiang et al. (2024)
Section C: Tertiary hybrid devices
Structural, chemical and electrical componentsPDMSPaper, glass, electrical componentsSoft lithography, laser ablation, stackingDetection of N. meningitidisDou et al. (2014)
Hole-punching, soft-lithography, laser ablationDetection of S. aureus and S. entericaZuo et al. (2013)
PMMAPolymethacrylic acid (as a copolymer), glass, paper and electrode componentsFree radical polymerisation and casting of copolymer and dry casting on glass. Biosensor integration into the deviceDetection of creatineTzianni et al. (2022)
Polyethylene terephthalate and paperLaser ablation and stackingUrine and blood analysisLaurenciano et al. (2021)
Microelectrode, carbon nanofibers-decorated gold nanoporous structuresLaser ablation, micromilling, electrode modificationDetection of prostate-specific antigenFelici et al. (2023)
Electrical components, aluminium, rubberElectrode functionalisation, laser ablation, stackingDetection of miR-122 and potential for diagnosis of drug-induced liver injuryRoychoudhury et al. (2023)
Electrical components, silicon, glassLaser ablation, stacking, solvent-assisted bondingBlood lysate preparationHaque et al. (2023)
GlassShape memory copolyacrylate, electrical componentsMicromoulding, photolithography, castingParticle separationYang et al. (2018)

Note: ‘Lab-on-a-chip’ refers to a generic application and is included where the author has not stated a particular application. Abbreviations: digital light processing (DLP), polymethyl methacrylate (PMMA), polydimethylsiloxane (PDMS), polyvinylchloride (PVC), ultraviolet (UV).

Section A of Table 1 lists microfluidic devices that can be categorised as a primary hybrid device and can be further divided into devices containing structural, chemical, or electrical hybrid components. Polydimethylsiloxane (PDMS) and polymethyl methacrylate (PMMA) are two of the most commonly used substrates in hybrid microfluidic device manufacture owing to their biocompatibility, flexibility in application, capacity to bond to a wide range of materials and cost-effectiveness (Nielsen et al., 2020). PDMS substrates can be easily modified to generate relatively complex 3D structures employing the widely used technique of soft lithography. However, although PDMS has proven a useful material for many applications, microchannels constructed of PDMS have been shown to absorb small molecules and deform under fluid pressure (Raj M and Chakraborty, 2020). These two issues can impact device functionality where the correct microchannel architecture or the quantification of biomolecules are critical for the application (Hou et al., 2017; Nielsen et al., 2020; Raj M and Chakraborty, 2020). PMMA, on the other hand, does not deform under fluid pressure, can be fully optically transparent, and has higher chemical inertness and greater biocompatibility than PDMS (Gencturk et al., 2017). Despite being one of the most widely used materials in microfluidic devices for cell biology applications, PMMA is not as versatile as PDMS when it comes to generating complex microchannel architectures (Gencturk et al., 2017). Other substrate materials have been used for structural hybrid devices, but their use may be limited by cost, complexity of fabrication technique or issues relating to chemical or biological compatibility. Glass generally has higher costs than thermoplastics but retains excellent biocompatibility, optical transparency and robustness (Hou et al., 2017). Likewise, despite some advantages, silicon lacks optical transparency and photosensitive resins often have poor biocompatibility (Ren et al., 2013; Hou et al., 2017).

As listed in Table 1, hybrid devices utilising PDMS often use soft-lithography and hybrid devices utilising PMMA often use laser ablation for manufacture. Laser ablation is a low-cost, highly replicable fabrication technique and can be used to cut or, etch PMMA at a much higher throughput rate than the use of soft lithography with PDMS (Gencturk et al., 2017; Hou et al., 2017). Generally, where hybrid devices in section A of Table 1 are categorized as having primary electrical or chemical components, a chemically or biologically inert material was used for the microchannel structure to act as a scaffold material for the chemical or electrically compatible material in order to perform their function.

Section B of Table 1 lists secondary hybrid microfluidic devices where materials have been combined to produce a structural channel whilst also simultaneously providing an electrical or chemical functionality. Similarly to primary component hybrid devices, the majority of listed devices are comprised of polymer materials as a base substrate and are often combined with glass, but more recently a range of other materials such as paper, hydrogels and other inorganic materials have also been used. Hydrogels have been used as bioscaffolds (Trappmann et al., 2017) for cell attachment whereas paper has been used as a fluid carrier (Chen et al., 2023). The photoresist SU-8 has extremely high biocompatibility and has historically been utilised as a critical material in microelectronics (Nemani et al., 2013). In some secondary hybrid devices, the coating of microchannels is used to convey a chemical functionality to an otherwise relatively chemical inert microchannel (Hesari et al., 2016) or may contain bioink materials for cell culture (Richard et al., 2020).

The third category, tertiary hybrid microfluidic devices, contain all three of the components discussed previously and a range of examples are listed in section C of Table 1. As before, polymers and glass are the primary substrate materials used in fabrication. Many of these devices utilise the electronic components purely as biosensors although some are used to generate electrical fields to enable a specific function in the device. It is of note that tertiary hybrid devices often have greater complexity and by definition are comprised of more materials than those classified as primary or secondary hybrid devices.

Conclusion

Many microfluidic devices are comprised of at least two materials, but modern multifunctional devices often use more. This review provides an important, but not exhaustive, review of current hybrid material microfluidic devices and proposes a new categorisation system for devices made of multiple materials. Whilst hybrid devices have not previously been systemically categorised, this review aims to provide a new approach to describe intra- and intergroup commonalities, and an insight into why different materials were selected for combination. The development of devices using multiple, diverse materials to achieve complex functionality requires the use of a range of manufacturing techniques, and this review further aims to aid researchers in their selection of materials for future hybrid device fabrication. We acknowledge that as microfluidic device functions increase in complexity with the integration of more materials this review may require updating in the future.

Author contributions

TC: Conceptualization, Data curation, Methodology, Writing–original draft. PB: Supervision, Writing–review and editing. AF: Supervision, Writing–review and editing. HB: Conceptualization, Supervision, Writing–review and editing.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Statements

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by Medical Research Scotland (grant number 50167-2019) and internal research funding from NHS National Services Scotland.

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Carvell, T., et al. (2024). Categorising hybrid material microfluidic devices. Frontiers in Lab on a Chip Technologies, Volume 3. https://doi.org/
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Copyright © 2024 Carvell, Burgoyne, Fraser and Bridle.

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*Correspondence: Helen Bridle

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