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Frontiers in Lab on a Chip Technologies ·

Volume 5 - 2026 | https://doi.org/10.3389/frlct.2026.1820279

The added value of micro-nanotextured surfaces integrated in microfluidics and lab-on-a-chip

  • Athina S. Kastania1
  • Evangelos Gogolides1,2
  • Angeliki Tserepi1,2*corresponding author
  1. 1Institute of Nanoscience and Nanotechnology, National Centre for Scientific Research “Demokritos”, Athens, Greece
  2. 2Nanoplasmas P.C., Athens, Greece
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Abstract

In the last 20 years, micro- and nano-textured surfaces have been produced by means of various surface engineering processes, imparting enhanced properties, such as tunable wettability from superhydrophilicity to superhydrophobicity, tunable optical, and antifouling or antibacterial properties, to the substrates on which micro-nanotexturing has been imposed. While these properties have been readily explored in open substrate surfaces presented in numerous publications, their implementation in microfluidic and lab-on-a-chip devices is less frequent although increasingly important through the incorporation of such surfaces as microfluidic walls. In this review article, we will focus on microfluidic and lab-on-a-chip devices in which micro-nanotextured surfaces have been integrated as passive valves and means of liquid transport, sensitive sensors, enhanced bacteria capturing and lysing devices, only to mention a few of their enhanced functionalities. The added-value of the incorporated surfaces in the device performance will be presented and analyzed. The aim is to provide a systematic elucidation into the multifaceted advantages and enhanced functional capabilities of micro-nanotextured surfaces when integrated within microfluidic systems.

Keywords

1 Introduction

Micro-nanotexturing is the process of geometrical modification of the topography of a surface by creating random, hierarchical micro and nanoscale features, such as micro and nano columns, pillars, cones, grooves or pores, that alter the surface properties. Such surface modification results in unique features that enhance functions such as the wettability (hydrophobicity/hydrophilicity) (Di Mundo et al., 2008), cell-surface interaction (Tserepi et al., 2016), light control (e.g., antireflectivity) (Vourdas et al., 2009) or solar cell efficiency (Chen, 2022). The terms “micro nanotexturing” and “micro nanotextured surfaces” first appeared in the academic literature in 2006 (Tserepi et al., 2006; Yi et al., 2006) to describe the modification of the surface topography of polymer or metal surfaces to result in the creation of superhydrophobic (SH) surfaces for potential use in microfluidics and “intelligent” implants, respectively. Since then, several review articles have been published, focusing on various unique features of micro-nanotextured surfaces and their implementation in a) the wetting control of plasma engineered polymer surfaces (Palumbo et al., 2019), b) tunable cell adhesion of laser-processed Si surfaces for tissue engineering applications (Stratakis et al., 2011), c) novel hydrodynamic properties of superhydrophobic surfaces for liquid transport, such as giant effective slip, superfluidity and mixing (Vinogradova and Dubov, 2012), d) biointerface functionality (Pratap and Patra, 2021), and e) optical, electronic, biomedical and mechanical engineering applications of milling-based microtexturing of surfaces (Jiang et al., 2024).

In addition to review articles, a large number of regular articles have appeared in the literature on micro-nanotextured surfaces and their unique performance, indispensable for a variety of applications. Examples of enhanced performance include surface property control (Gogolides et al., 2010; Aizawa et al., 2019), tunable wettability (Di Mundo et al., 2008; Jiang et al., 2017; Rehman et al., 2025), wickability of metal surfaces (Li et al., 2023), control of nanotribological properties such as friction coefficient (Zhao et al., 2010; Hao et al., 2018; Xi et al., 2023) and their application in MEMS. Other examples include remarkable transport properties such as drag reduction, large effective slip and amplified electrokinetic pumping (Rothstein, 2010; Vinogradova and Belyaev, 2011; Sekeroglu, 2014; Solomon et al., 2014) for application in microfluidics, water and dew harvesting (Nioras et al., 2022; 2024). Finally, enhanced biomolecule immobilization (Kunduru et al., 2010; Vlachopoulou et al., 2011; Tsougeni et al., 2018) for sensitive detection of target substances, tunable cell adhesion and growth (Khademhosseini et al., 2007; Wang et al., 2008; Koufaki et al., 2011; Mahmood et al., 2014; Islam et al., 2015b; Bourkoula et al., 2016; Mansur et al., 2017; Diaz Lantada et al., 2020; Zhang et al., 2025) for application in tissue engineering, enhanced cancer cell isolation, or antithrombotic performance of medical implants, and artificial antibacterial surfaces (Balčytis et al., 2015; Ellinas et al., 2017a; Nioras et al., 2025) are some of the unique properties reported.

Despite the large number of publications on micro-nanotextured surfaces, the majority of them deals with open substrate surfaces and only one-third of them with the incorporation of such surfaces into microfluidics and lab-on-a-chip (LoC) devices, as shown in Figure 1A. In this review article, we will focus on microfluidic and LoC devices in which micro-nanotextured surfaces have been incorporated to add or enhance the device functionality, such as passive valving, sensitive sensing, enhanced bacteria capturing and lysing, to mention only a few of their unique device features. In addition to the added-value in the device performance, the fabrication methods of the incorporated surfaces will be reviewed (the main of which are shown in Figure 1B) and a variety of the micro-nanotextured device applications will be presented.

**(A)** Publications (source: google scholar) in the last 20 years with the topics “micro nanotextured surfaces” (total number, in red) and “microfluidics with incorporated micro-nanotextured surfaces” (in green) and **(B)** main techniques for roughening of microfluidic surfaces and corresponding SEM images (*clockwise* for SEM images*:* top left) adapted from *Biomed. Microdevices,* Vol. 22, Kastania et al., 44, 2020, with permission from Springer Nature, top right) adapted from Source: Wang et al., *PhotoniX* 2022, DOI: 10.1186/s43074-021-00033-1. Reproduced under the Creative Commons Attribution 4.0 International License (CC BY 4.0), bottom right) adapted from *Microchimica Acta*, Vol 188, *Arshavsky-Graham et al.*,67, 2021, with permission from Springer Nature, and bottom left) adapted from Gabardo et al. (2015a) with permission from the Royal Society of Chemistry).
Figure 1. (A) Publications (source: google scholar) in the last 20 years with the topics “micro nanotextured surfaces” (total number, in red) and “microfluidics with incorporated micro-nanotextured surfaces” (in green) and (B) main techniques for roughening of microfluidic surfaces and corresponding SEM images (clockwise for SEM images: top left) adapted from Biomed. Microdevices, Vol. 22, Kastania et al., 44, 2020, with permission from Springer Nature, top right) adapted from Source: Wang et al., PhotoniX 2022, DOI: 10.1186/s43074-021-00033-1. Reproduced under the Creative Commons Attribution 4.0 International License (CC BY 4.0), bottom right) adapted from Microchimica Acta, Vol 188, Arshavsky-Graham et al.,67, 2021, with permission from Springer Nature, and bottom left) adapted from Gabardo et al. (2015a) with permission from the Royal Society of Chemistry).

2 Micro-nanotextured surfaces in microfluidics and lab-on-a-chip: fabrication technologies, enhanced properties, and applications

Supplementary Table S1 (Supplementary Material) contains the publications focusing on the incorporation of micro-nanotextured surfaces in microfluidics and lab-on-a-chip devices, together with the properties/functionalities imparted to the devices, the fabrication technologies through which such surfaces are realized, and the applications enabled by such devices. The same publications are accounted for in Figure 1A together with the progress of the technologies in this research area. The following subsections present the technologies implemented for the realization of the textured surfaces, the enhanced properties imparted to the devices and their applications.

2.1 Micro-nanotexturing technologies for microfluidics

The first microfluidic chip is attributed to Terry et al. (1979) pioneering a miniaturized and efficient gas chromatography microcolumn on a silicon chip. Afterwards and over the past 45 years, the microfluidics field has evolved to meet a wide range of applications. Traditionally, early microfluidic channels and Lab-on-chips have been fabricated by means of the wide-spread semiconductor microfabrication technology. However, new fabrication methods have been adapted or invented to include a wide variety of processing steps from lithography and wet or dry etching, stamping and CNC machining to surface chemical modifications and sealing. Several of these fabrication techniques result in roughening of the surfaces inside microchannels, either intentionally or not. The topography of these micro-and nanotextured surfaces typically consists of random micro and/or nanofeatures in the form of micro- or nanopillars, wires, filaments, etc., and/or bigger aggregations of them (bundles). Moreover, this random architecture should be considered different from the well-patterned micro- or nanofeatures following specific CAD designs, which are not included herein. Microfluidic surfaces are roughened via micro-nanotexturing through various processes (the main ones are depicted in Figure 1B), such as laser and plasma processing, CNC machining, wet processing, or other advanced techniques. Table 1 shows the fabrication methods in increasing order of roughness size and thus far roughness demonstrated tunability in the micro-nanoscale.

TABLE 1. Surface roughness size and its tunability for various fabrication methods of microfluidic devices (indicative references).

Fabrication methodRoughness sizeRoughness tunabilityReferences
Wet processingUp to some hundreds of nm+ (tunable in low scale; mainly smooth surface)Arshavsky-Graham et al. (2021a), 2021b
Plasma processingSome nm to several μm in height++Kastania et al. (2020), Tsougeni et al. (2024)
Laser processingSome nm to several μm in height++Babaliari et al. (2025)
Spray-depositionHundreds of nm to tens of μm+Ghosh et al. (2014)
Oblique angle polymerizationSubmicron size+Sekeroglu and Demirel (2015)
Shrinkage properties of PSFrom nm to μm scale++Gabardo et al. (2013), 2015a; 2015b
Al-crystallization (AIC)Tens of nm to μm+Wang et al. (2008)
ZnO sputtering on cold rolling manufactured Al sheetsTens of nm+Tao et al. (2020)
PDMS moldingHundreds of nm-Hasan et al. (2018)
CNC machining0.2 μm to tens of μm+ (tunable in micro-scale)Ghobeity et al. (2012)
3D-printingμm-Zhang et al. (2020)

++ highly tunable in micro-nanoscale.

+ tunable in micro-nanoscale.

  • non-tunable in micro-nanoscale.

2.1.1 Plasma micro-nanotexturing

Gaseous plasma technology has been utilized toward surface activation, etching and deposition on a variety of materials. As a micro-nanotexturing etching tool, it has shown versatility and is been used to simultaneously provide both active groups and roughness on surfaces by controlling various plasma process parameters, such as time, bias voltage, gas, rate, source power, etc., (Ma et al., 2023). The roughness can selectively be in the range of some nm to several μm in height. Depending on the supplied gas, one can target various substrate materials for microfluidics from Si wafers and glass to polymers, using Fluorine- or Oxygen-containing plasma. Preparation of black Si (bSi) through plasma etching (mixtures of SF6 and O2) with pencil-like nano-spikes is reported (500 nm high with 95 nm pillar diameter) and integrated in microfluidics (Seniutinas et al., 2015; Wang et al., 2016) as well as cryogenic etching processes of Si are used for tunable roughness of bSi (70 nm–3.8 μm) in microfluidics (Rahali et al., 2025).

Although silicon and glass are indeed two of the most common microfluidic materials in early microfluidics, polymer has emerged as a significant alternative due to lower cost, biocompatibility, repeatability and manufacturability (Han et al., 2022), which is the reason of its wide-spread use in Lab-on-chips in recent years. More specifically, plasma etching enables controlled micro-nanotexturing of polymer surfaces for improved cell adhesion, proliferation, and advanced microanalytical applications by tailoring their chemistry and topography (Tserepi et al., 2016). Studies have shown that when MEMS technology was employed including either lithography directly on the polymer surface and plasma etching (Kastania et al., 2016; Tsougeni et al., 2016; 2019) or Computer Numerical Control (CNC) milling or hot-embossing followed by plasma etching through a stencil mask (Kastania et al., 2020; Tsougeni et al., 2024), the microfluidic surfaces are micro-nanotextured with a roughness height from some nm to several of μm depending on the plasma process time or other conditions (Tsougeni et al., 2010b; Kanioura et al., 2020). These plasma micro-nanotextured microfluidics are utilized as such, for example, for solid phase extraction towards DNA purification (Kastania et al., 2016), where the created high surface area on the microchannel walls plays the role of the solid support. Moreover, either by further coating the surface with various materials such as specific biomolecules including proteins, polypeptides and antibodies, for selective biocapture (Tsougeni et al., 2016; 2024; Kastania et al., 2017; 2020) or with PEG-based compounds for stabilization of the surface hydrophilicity (Cunaj et al., 2018), or through plasma deposition of, e.g., C4F8 for surface hydrophobization, these micro-nanotextured polymeric microfluidics obtain active wall surfaces with wetting properties that can affect the flow of the fluids inside them (Tsougeni et al., 2010a; 2014; Papageorgiou et al., 2013; Ellinas et al., 2014). As a result, appropriate surface chemistry and morphology are imparted to the microchannel surface, enhancing the inherent properties of the microfluidic device. Finally, plasma etching can also be used in combination with other techniques such as colloidal lithography to provide nanotexturing which imparts superhydrophobicity through the deposition of hydrophobic fluorocarbon layers on the microchannel surfaces (Prakash et al., 2013; 2014).

In summary, a plethora of publications in the literature describe microchannels being micro-nanotextured via plasma processing, utilizing the roughening outcome that can be precisely controlled on demand (nm up to μm), thereby enhancing the properties of microfluidic devices suitable for a variety of applications.

2.1.2 Wet processing

Wet etching and particularly wet anisotropic etching is a traditional method to form Si microfluidic channels after a lithographic step. Following lithography, the wet anisotropic etching with solutions such as NaOH solution or NH2OH-added NaOH solution, KOH solution, TMAH, H3PO4, HF, etc., results in surface roughness that varies depending on etching time, the etchants used, their concentration as well as their age (Purohit et al., 2022). Another wet etching technique includes an anodic electrochemical process in solution of HF and ethanol followed by an oxidation step for fabrication of porous silicon (PSi, cylindrical pores with ∼50 nm diameter, ∼75% porosity) which is then integrated in 3D-printed microchannels (Arshavsky-Graham et al., 2021a; 2021b).

Besides wet etching, other wet processes have emerged that produce textured surfaces which can be integrated in microfluidics, for example, the hydrothermal growth of metal oxides such as ZnO (Xesfyngi et al., 2023). After extended wet treatment, elongated ZnO nanorods of diameters in the range 130–400 nm can be grown. PDMS microfluidic channels are also modified via on-chip injection of H2SO4 solution (chemical modification) or by transferring paper textures in PDMS channel walls and injecting acetone solution with TiO2 nanoparticles (physical modification) (Li et al., 2015). Both of these techniques provide a nanotexturing effect enhancing the non-wetting properties of the channels.

Other works include fabrication of micro-nano hierarchical dendritic structures via Cu evaporation and replacement reaction between Cu-coated surface and AgNO3 solution towards droplet manipulation (Wang et al., 2020) or clustered copper hydroxide nanoneedles (∼200 nm thick) on Cu laser-micromachined tracks by immersion in solutions of sodium hydroxide and ammonium persulfate, followed by functionalization with perfluorodecanethiol (Stamatopoulos et al., 2020).

Wet processing is one of the first and less complicated methods used to, etch and texture materials, the outcome of which is often a smooth or nanotextured surface with roughness size being confined in the nanometer scale.

2.1.3 Laser processing

Laser ablation has been introduced as an alternative fabrication method to wet-etching of glass or polymer microdevices due to lower process time and cost-effectiveness, with microfluidic channels as fabricated having higher surface roughness than the wet etched channels (Baker et al., 2011). Many different types of lasers are used from fibre laser and CO2, to excimer laser (e.g., Ar-F or Kr-F laser) and femtosecond laser.

Singh et al. studied the effect of Kr-F laser parameters such as laser energy, frequency and speed on specific polymethylmethacrylate (PMMA) microchannel characteristics including depth, wall angle and surface roughness; the best laser processing conditions with which repeatability was achieved were for a roughness of 2.2 μm in a microchannel of 44 μm depth and 195 μm width (Singh et al., 2025). In their work, they showcased that the roughness outcome can be controlled leading to hydrophobic surfaces embedded in the channels. Wang et al., using a CO2 laser, engraved structures on PMMA, which are then transferred via soft lithography on PDMS and laser nanotextured afterwards (Wang et al., 2021).

Ultrafast laser processing enables nowadays precise three-dimensional micro- and submicron surface structuring through nonlinear absorption processes. Laser technology offers high fabrication speed, non-contact processing, broad material compatibility, and the ability to create complex 3D geometries that are difficult to achieve with conventional planar techniques (Stratakis et al., 2011). Moreover, Laser-Induced Periodic Surface Structures (LIPSS) and microgrooved structures are widely used for various applications and are integrated in microfluidics as well (Babaliari et al., 2025). Gaddam et al. fabricated dual texturing topographies (LIPSS and microscale features) on stainless steel surfaces within microchannels using a femtosecond laser processing and further functionalized them with silane making them superhydrophobic (Gaddam et al., 2021). Other works involve femtosecond machining (158 fs pulses, 1 kHz Ti-sapphire laser) of micro-grooved structures in microchannels, so that hydrophilic or even superhydrophilic surfaces are created at specific regions in the channels (Goya et al., 2017).

Overall, laser processing has emerged as a quick nanotexturing process through which microfluidics can be fabricated with an obtained surface roughness size from μm down to several nm.

2.1.4 CNC machining and milling-based texturing

Computer numerical control (CNC) precision machining including drilling, turning, mechanical grinding, and Electrical Discharge Machining (EDM), is a well-established and fast method for fabrication of microchannels (Mohamed Rijal et al., 2024) and channel replication molds via removal of bulk material. The resulted surface roughness which may be in the range of 0.2 μm to tens of μm depends on the cutting settings such as the speed, the tool diameter size, etc. In most cases, the roughness created is undesirably high, with many efforts made towards reducing its size. For example, Zhou et al. fabricated first via milling a positive acrylate master with high surface roughness (Ra = 6.34 × 102 μm) and tried to limit the transfer of the roughness to the molded PDMS microchannel by adjusting the time and temperature of the pre-curing step (Zhou et al., 2017). Other machining methods are also reported such as abrasive jet micromachining (AJM) for microfabrication of microfluidics through an erosion-resistant mask (Ghobeity et al., 2012). The surface roughness (Ra) of the microfluidics was in the range of 0.4–0.6 μm, but when compared to smoother wet etched microfluidics (Ra in the range of 0.002–0.005 μm) they resulted in similar electro-osmotic mobility and LoD. However, the AJM chips showed lower separation efficiency, further confirming that the obtained high roughness is undesirable.

Research on milling-based micro-texturing technology is still in an exploratory phase, with limited use in manufacturing (Jiang et al., 2024). The selection of the milling tools is crucial to achieve precision and reduce surface roughness, which is now in the range of μm (up to mm), with a potential down to the nanoscale.

2.1.5 Other advanced techniques for microchannel roughening

Additive manufacturing (3D printing) has recently revolutionized the fabrication of microfluidic devices, due to lower waste and its capability to rapidly create sealed devices together with fluidic interconnects, thus greatly simplifying their rapid prototyping. However, the produced 3D-printed microchannels exhibit a quite high surface roughness (Zhang et al., 2020) that is in most cases undesirable, as it cannot be tuned. Efforts are made for reducing its size (Mohamed Rijal et al., 2024). Zhang et al. have tried combining 3D printing of microchannels with successive PDMS coating layers to reduce the roughness size from tens of μm to submicron scale (Zhang et al., 2020).

Furthermore, micro-nanotexturing on open microfluidics can be achieved by spray-deposition of a dispersion mixture consisting of a hydrophobic PMC copolymer, TiO2 nanoparticles, and ethanol onto various types of substrates (aluminum, polymer, and paper) rendering them superhydrophobic (Ghosh et al., 2014). Next, UV irradiation of the substrates through a photomask results in wettability patterning (superhydrophilic and superhydrophobic regions) with surface roughness in the range of hundreds of nm to tens of μm.

Fabrication via oblique angle polymerization of poly(p-xylylene) (Parylene or Nano-PPX) also induces nanotexturing with clusters of nano-rods (of submicron size) formed on surfaces (Sekeroglu and Demirel, 2015). These Nano-PPX surfaces are hydrophobic and can be subjected to plastic deformation to create tracks for guided transport of droplets. Furthermore, a benchtop fabrication process is used for creation of wrinkled gold micro-nanotextured electrode structures on shrink memory polymers (pre-stressed polystyrene (PS)) integrated with microfluidics (Gabardo et al., 2015a). In this work, Gabardo et al. exploit the shrinkage properties of PS after heating above its glass transition temperature to induce wrinkling of the electrode material. The electrodes’ features range from the nanometer to the micrometer scale and can be tailored by varying the film thickness of the patterned electrodes and the shrinking temperature (Gabardo et al., 2013; 2015a; 2015b).

Moreover, Al-crystallization (AIC) technique of a-Si films is employed and the resulting microtextured (MTS) and nano/microtextured surfaces (NMTS) are based on a nucleation process during the Al annealing step with average particle height of 460 nm and 30 nm for MTS and NMTS, respectively (Wang et al., 2008). Finally, other works include cold rolling manufactured Al sheets coated with ZnO films via sputtering, which provide a hierarchical topography with a mean roughness of 73.6 nm (Tao et al., 2020) or utilize the unpolished backside of a silicon wafer as a template for PDMS molding toward surface nanotexturing of PDMS channels with roughness root mean square (RMS) of 682 nm (Hasan et al., 2018).

The various advanced techniques described above produce textured surfaces with an induced roughness size depending on the method. These works include 3D printing and individual laboratory efforts from spray-deposition to crystallization and specific property exploitation and are mainly distinct cases that more often need specialized tools and expertise as well as further research investigation. Among these techniques, 3D printing is a new, ever-evolving technology that has not been utilized yet for tunable, 3D printing-induced roughness in microfluidics, but is expected in the future to control roughness size due to its widespread use and anticipated progress.

2.2 Enhanced device properties and their applications

In Table 2, the properties attributed to microfluidic devices due to the incorporation of textured surfaces are shown together with their applications. In Figure 2, representative microfluidic devices integrated with micro-nanotextured surfaces and their functional properties are presented. Each of their enhanced properties and their applications will be discussed in detail in this section.

TABLE 2. Properties attributed to microfluidic devices by incorporating textured surfaces, their fabrication methods, applications, and micro-nanotexture parameters to device performance metrics.

PropertyReferencesApplication and fabrication methodMicro-nanotexture parameters to performance metrics
High roughness/Surface areaBaker et al. (2011), Mall et al. (2011), Ghobeity et al. (2012), Gabardo et al. (2013), 2015a; Stamatopoulos et al. (2020), Tao et al. (2020), Mandev and Manay (2022), Mohamed Rijal et al. (2024)Electrophoretic separation, fluid transport, electrochemical analysis, heat-exchangers Wet processing in 1 article Laser processing in 1 article CNC machining in 1 article Other adv. technologies in 3 articles- Roughness Ra = 3 μm led to a 40% increase in convective heat transfer- 30 μm roughness height led to a 20% of pressure drop reduction was predicted in microchannels 90 μm deep- Rq ∼ 250–1,200 nm led to sensitive electrochemical analysis thanks to up to 1,000% enhanced electrode surface area- Roughness height 1–2 μm controls electroosmotic flow (reduction or increase depending on the surface hydrophilicity)
Wettability control/SHTsougeni et al. (2010a), Vinogradova and Dubov (2012), Papageorgiou et al. (2013), Prakash et al. (2013), 2014; Ellinas et al. (2014), 2017b; Ghosh et al. (2014), Kaler and Prakash (2014), Li et al. (2015), Sekeroglu and Demirel (2015), Cunaj et al. (2018), Stamatopoulos et al. (2020), Tao et al. (2020), Wang et al. (2020), 2021; Gaddam et al. (2021), Sinha Mahapatra et al. (2022), Rahali et al. (2025)Liquid transport (bulk and droplet), separation, molecular diagnostics, geoscience Wet processing in 3 articles Plasma processing in 8 articles Laser processing in 2 articles Other adv. technologies in 3 articles- 11 μm high micro- nanocolumns led to capillary velocity of 200 μm/s- Micro-nanocolumnar structures, 100–1,000 nm high, led to passive valving with Pth = 48–84 mbar- Hierarchical SH hills, 2–3 μm high, led to 20% pressure drop reduction- Micro (0.72 μm) and nano-roughness (73.6 nm) was used for droplet transport (inclination 0° < α ≤ 180°)- Hydrophobized nanoneedles (200 nm-thick) were used for droplet self-propulsion
Biomolecule bindingTsougeni et al. (2012), 2016; 2019, 2024; Gianneli et al. (2016), Kastania et al. (2016), 2020; Goya et al. (2017), Arshavsky-Graham et al. (2021a), Vorvi et al. (2024)Protein, enzyme and bacteria detection, DNA purification Wet processing in 1 article Plasma processing in 8 articles Laser processing in 1 article- Surface roughness enhanced active surface area up to 500%–1,000% and led to sensitive detection of biomolecules by 2 orders of magnitude- 5 μm high hierarchical hills, 5 μm apart, captured bacteria with 10–100 times enhanced efficiencies (depending on bacteria concentration)
Cell-surface adhesion/ProliferationWang et al. (2008), Tsougeni et al. (2014), Islam et al. (2015a), 2016; Kastania et al. (2017), Hasan et al. (2018), Kanioura et al. (2020), Babaliari et al. (2025)Selective cell attachment, bacteria-based microsensors, separation, enrichment and detection of tumor cells Plasma processing in 5 articles Laser processing in 1 article Other adv. technologies in 2 articles- Nanoparticles (30 nm in height, 0.66 μm in diam., and 5% surface coverage) led to enhanced (by > 2 times) bacteria-to-surface adhesion- Micro nanostructured (ultrafast laser processed) surfaces (roughness ratio of 1.6) were shown to inhibit differentiation of Neuro-2a cells- Hierarchical topography of mean height ∼800 nm was found appropriate for selective proliferation and enrichment (25–80x) of cancer cells- Antibody functionalized nanotextured surfaces (Rq∼680 nm) enhanced capturing (by 71% ± 19%) of cancer cells
Biocidal actionGabardo et al. (2015b), Wang et al. (2016), Xesfyngi et al. (2023)Cell lysis, DNA release Wet processing in 1 article Plasma processing in 1 article Other adv. technologies in 1 article- Black-Si nanospikes ∼500 nm high and 95 nm in diam. and ZnO nanospikes several μm in length and 130–400 nm in diam. were used for bacterial cell lysis- Micro-nanotextured electrodes lower the voltage (from 8 to 4 V) needed for electrical bacterial lysis and enhance the lysis efficiency to 100%
Representative examples of microfluidic devices with incorporated micro-nanotextured surfaces, imparting unique properties and their applications. **(A)** Schematic of a modular droplet chip (MDC) fabricated by laser processing, a superhydrophobic overpass embossed after laser modification and a SEM image of the nanotextured surface. Source: Wang et al., *PhotoniX* 2022, DOI: 10.1186/s43074-021-00033-1. Reproduced under the Creative Commons Attribution 4.0 International License (CC BY 4.0). **(B) i)** Inlet and outlet of patterned shrunken PS substrate and PDMS microchannel bonded to PS substrate and SEM image of the resulting wrinkled electrode structure. Adapted from (Gabardo et al., 2015a) with permission from the Royal Society of Chemistry, **ii)** Electrofluidic device with micro-nanotextured electrodes fabricated by polymer-induced wrinkling of Au and electrodeposition achieves efficient reagent-free bacterial lysis (higher than 95% at an applied potential of 4 V). Reproduced from (Gabardo et al., 2015b) with permission from the Royal Society of Chemistry. **(C)** Hierarchical nanotextured piezoelectric films (CYTOP/ZnO/Al) achieved acoustofluidics-based droplet transport on arbitrarily shaped surfaces. Source: Tao et al., Nano Lett. 2020, DOI: 10.1021/acs.nanolett.0c00005. Reproduced under the Creative Commons Attribution 4.0 International License. **(D)** Top-view and cross section HRSEM micrographs of oxidized PSi nanostructure and the resulting integrated 3D-printed microfluidic device with the Psi. Adapted from *Microchimica Acta*, Vol 188, *Arshavsky-Graham et al.*,67, 2021, with permission from Springer Nature. **(E)** Plasma micro-nanotextured PMMA surfaces, functionalized with polyclonal antibodies, captured bacteria with enhanced efficiencies from 10X to 100X depending on the bacteria concentration. Adapted from (Tsougeni et al., 2016), with permission from the Royal Society of Chemistry. **(F) i)** Schematic of a plasma micro-nanotextured microfluidic device and SEM images of the device and surface roughness. Adapted from *Biomed. Microdevices,* Vol. 22, Kastania et al., 44, 2020, with permission from Springer Nature, and **ii)** Plasma micro-nanotextured microchannels with superhydrophobic patch that acts as passive microvalve with controllable opening pressure. Reprinted from *Microfluid. Nanofluidics,* Vol. 17, Ellinas et al., 489–498, 2014, with permission from Springer Nature.
Figure 2. Representative examples of microfluidic devices with incorporated micro-nanotextured surfaces, imparting unique properties and their applications. (A) Schematic of a modular droplet chip (MDC) fabricated by laser processing, a superhydrophobic overpass embossed after laser modification and a SEM image of the nanotextured surface. Source: Wang et al., PhotoniX 2022, DOI: 10.1186/s43074-021-00033-1. Reproduced under the Creative Commons Attribution 4.0 International License (CC BY 4.0). (B) i) Inlet and outlet of patterned shrunken PS substrate and PDMS microchannel bonded to PS substrate and SEM image of the resulting wrinkled electrode structure. Adapted from (Gabardo et al., 2015a) with permission from the Royal Society of Chemistry, ii) Electrofluidic device with micro-nanotextured electrodes fabricated by polymer-induced wrinkling of Au and electrodeposition achieves efficient reagent-free bacterial lysis (higher than 95% at an applied potential of 4 V). Reproduced from (Gabardo et al., 2015b) with permission from the Royal Society of Chemistry. (C) Hierarchical nanotextured piezoelectric films (CYTOP/ZnO/Al) achieved acoustofluidics-based droplet transport on arbitrarily shaped surfaces. Source: Tao et al., Nano Lett. 2020, DOI: 10.1021/acs.nanolett.0c00005. Reproduced under the Creative Commons Attribution 4.0 International License. (D) Top-view and cross section HRSEM micrographs of oxidized PSi nanostructure and the resulting integrated 3D-printed microfluidic device with the Psi. Adapted from Microchimica Acta, Vol 188, Arshavsky-Graham et al.,67, 2021, with permission from Springer Nature. (E) Plasma micro-nanotextured PMMA surfaces, functionalized with polyclonal antibodies, captured bacteria with enhanced efficiencies from 10X to 100X depending on the bacteria concentration. Adapted from (Tsougeni et al., 2016), with permission from the Royal Society of Chemistry. (F) i) Schematic of a plasma micro-nanotextured microfluidic device and SEM images of the device and surface roughness. Adapted from Biomed. Microdevices, Vol. 22, Kastania et al., 44, 2020, with permission from Springer Nature, and ii) Plasma micro-nanotextured microchannels with superhydrophobic patch that acts as passive microvalve with controllable opening pressure. Reprinted from Microfluid. Nanofluidics, Vol. 17, Ellinas et al., 489–498, 2014, with permission from Springer Nature.

2.2.1 Roughness and effective surface area

Αn obvious consequence of micro-nanotexturing of surfaces is the enhancement of their surface roughness and consequently of their effective surface area. In some cases, an effective surface area increase by as much as 500% has been reported, for (1 h) plasma-etched polymeric surfaces with simultaneous co-deposition of etch inhibitors from the reactor walls (Tsougeni et al., 2010b) that forms micro- and nanocolumns 25 μm in height.

Increased surface roughness affects both fluid flow and heat transfer in microfluidics (Mohamed Rijal et al., 2024), finding application in diagnostic microdevices and heat micro-exchangers. Regarding the latter, it was determined that surface roughness had a significant effect on mixed convective heat transfer and microchannel roughness Ra =3 μm (in a 300 μm deep microchannel) led to an increase of about 40% in convective heat transfer relative to conduction (Mandev and Manay, 2022). Regarding the former, generally speaking, the microchannel roughness affects liquid transport in microfluidics, as it contributes to increased slip length over channel height ratio and thus to pressure drop reduction, facilitating liquid flow inside rough microchannels (Mall et al., 2011). In fact, a 20% of pressure drop reduction was predicted in microchannels of depth similar to the roughness height (90 μm).

However, the effect of increased roughness of microchannel surfaces on electroosmotic flow velocity is controversial in the literature; slightly lower (<15%) electroosmotic flow velocity has been reported for rough (Rq = 1.28 μm), laser-ablated microchannels, compared to their smooth (Rq = 0.02 μm) wet-etched counterparts (Baker et al., 2011). On the contrary, rough (2 μm roughness height) and hydrophilized plasma-etched microchannels have been reported to exhibit higher (by 40%) electroosmotic flow velocity compared to their smooth counterparts (Vourdas et al., 2008), attributed not only to the surface roughness but also to the chemical and wettability changes, induced by plasma processing. In addition, in rough microchannels (Ra = 0.4–0.6 μm) (Ghobeity et al., 2012), a reduction in separation efficiency (∼4–5x) has been reported compared to smooth microchannels, probably as a result of enhanced mixing in rough microchannels. In cases where textured surfaces, with Rq ∼ 250–1,200 nm, are implemented as electrode surfaces after metal (e.g., gold) deposition, electroactive surface area enhancement in excess of 1,000% was observed when compared to flat electrodes (Gabardo et al., 2013), thus leading to sensitive electrochemical analysis (Gabardo et al., 2015a).

Summarizing, increased surface roughness in the micro and nanoscale was shown to favor heat transfer by convection by as much as 40% (for Ra = 3 μm), pressure-driven fluid flow with as much as 20% pressure drop reduction (for roughness height = 90 μm), sensitive electrochemical analysis thanks to an enhanced electrode surface area by 1,000% (for Rq ∼ 250–1,200 nm), and control of the electroosmotic flow (lower or higher, depending on the surface hydrophilicity, for roughness height in the range 1–2 μm).

2.2.2 Wettability control/superhydrophobicity

Roughness affects the surface wettability, which constitutes the most widespread functional property of textured surfaces in microfluidics. Wettability control, mainly at its extremes (superhydrophobicity/superhydrophilicity), affects bulk and droplet liquid transport, as it has been demonstrated in numerous articles. Specifically, it has been shown that superhydrophilicity favors capillarity and pumpless liquid transport in closed and open microchannels (Tsougeni et al., 2010a; Cunaj et al., 2018; Sinha Mahapatra et al., 2022), while superhydrophobicity (SH) when applied in selected spots in microchannels serves as passive on-off valving (Tsougeni et al., 2010a) with tailored opening pressure (Ellinas et al., 2014), depending on the processing conditions of the SH spots. Such SH on-off valves have been applied in microfluidic devices performing bead-based immunoassays for protein detection (Ellinas et al., 2017b).

The effect of superhydrophobicity on liquid transport in microfluidics is discussed in general terms in (Vinogradova and Dubov, 2012) as superhydrophobic surfaces are predicted to induce novel hydrodynamic properties such as giant effective slip, superfluidity and mixing, and affect electrokinetic phenomena, that can all be exploited in microfluidics and lab-on-a-chip devices. Indeed, a pressure drop reduction by as much as 22% has been demonstrated in SH microfluidic channels bearing 2–3 μm high, hierarchical SH hills (Papageorgiou et al., 2013), while flow enhancement and hydrodynamic drag reduction leading to minimization of pumping power requirements has been demonstrated in (Gaddam et al., 2021).

The topographical and chemical modification of flexible piezoelectric films (Al sheet coated with nanostructured ZnO) exhibiting micro (0.72 ± 0.05 μm) and nanoroughness (73.6 nm) has been also used for droplet transportation in digital microfluidics at wide range of inclination angles (0° < α ≤ 180°) (Tao et al., 2020). Nanoneedles (200 nm-thick) formed by chemical reactions on copper tracks which were hydrophobized were also used for droplet self-propulsion, making needless the implementation of external, active droplet actuation (Stamatopoulos et al., 2020). Droplet transport (Li et al., 2015; Wang et al., 2020), self-propulsion (Wang et al., 2021), and liquid electrophoresis (Prakash et al., 2013) have been demonstrated in nanotextured digital microfluidics (Ghosh et al., 2014; Kaler and Prakash, 2014) in which real-time polymerase chain reaction (PCR) for DNA amplification has been also demonstrated (Prakash et al., 2014). Finally, asymmetric orientation of nanotextured surfaces has found application in droplet manipulation (merging and sorting (Sekeroglu and Demirel, 2015), while patterned wettability of surfaces has found application in geoscience (Rahali et al., 2025), as microchannel roughness mimics roughness observed on natural rock minerals.

In summary, controlled surface roughness easily leads to wettability control at its extremes (superhydrophobicity/superhydrophilicity), exploited in pump-less liquid transport, passive valving, flow enhancement, and droplet manipulation in microfluidics and LoC devices.

2.2.3 Biomolecule adsorption/binding

The high effective surface area (enhanced by surface roughness up to 500%–1,000%, as discussed in 2.2.1), often combined with the chemical modification of nanotextured surfaces, favors enhanced capacity for biomolecules immobilized on such surfaces (Vlachopoulou et al., 2008). This capacity of micro-nanotextured surfaces was quickly exploited in microfluidic channels (Tsougeni et al., 2012) and relevant devices (sensors (Gianneli et al., 2016), bioassay chips (Goya et al., 2017) (with microgrooves 8 μm apart) and microfluidics (Tsougeni et al., 2016) (with 12 μm high hierarchical posts, 5 μm apart)). Indeed, extremely sensitive detection of proteins higher by two orders of magnitude was demonstrated in rough microchannels compared to smooth ones (Tsougeni et al., 2012).

This remarkable sensitivity was leveraged in microfluidic devices functionalized with polyclonal antibodies for efficient bacteria capture in food-borne (e.g., Salmonella) and environmental (e.g., Legionella) pathogen detection (Tsougeni et al., 2016; 2019; 2024). Indeed, bacteria were captured on plasma micro-nanotextured surfaces (bearing 5 μm high hierarchical hills, 5 μm apart) with highly enhanced efficiencies, from 10 to 100 times higher compared to flat microfluidic surfaces, depending on the bacteria concentration (100% for bacteria concentrations up to 105 cells/mL, decreasing to 10% for bacteria concentrations 108 cells/mL).

In addition to antibodies, other biomolecules, such as aptamers, were immobilized on rough surfaces for sensitive detection of target proteins (Arshavsky-Graham et al., 2021a) and enzymes (such as HRP) in an enzymatic microreactor for biocatalytic oxidation of phenols (Vorvi et al., 2024). Furthermore, the enhanced effective surface area (6-fold surface area increase for 20 min plasma treatment (Tsougeni et al., 2009; 2010b) of microchannel walls can provide highly dense surface chemical groups that have been exploited for the binding of biomolecules, such as DNA (Kastania et al., 2016; 2020) in devices for DNA purification, before its downstream amplification and sensitive detection in microfluidics for molecular diagnostics.

Overall, the high effective surface area of textured microfluidics and relevant devices (sensors, bioassays), enhanced by surface roughness up to 500%–1,000%, has been exploited in enhanced immobilization of antibodies, aptamers, DNA, and enzymes for highly sensitive detection of target biomolecules and bacteria, by two orders of magnitude, in properly designed microfluidics, LoC devices, and biomicroreactors.

2.2.4 Controlled cell adhesion/proliferation

Control of cell-to-surface adhesion is important to many biological and bioanalytical applications such as tissue engineering, diagnostics, and biosensors. It is generally accepted that cellular adhesion to a surface is controlled by the chemical and physical characteristics of the surface, such as hydrophobicity and hydrophilicity, surface charge, and mainly surface roughness. The enhanced surface area of micro-nanotextured surfaces formed by nanoparticles (30 nm in height, 0.66 μm in diam., and 5% surface coverage fraction) is found to lead to enhanced (by > 2 times) cell-to-surface adhesion over smooth surfaces, with application in the realization of bacteria-based sensors (Wang et al., 2008). In addition to the high surface roughness, wettability patterning results in superhydrophilic and superhydrophobic micro-nanotextured areas inside the channel (Tsougeni et al., 2014). Cells attach selectively on superhydrophilic micro-nanotextured channel surfaces with no attachment on SH ones, which can be applied to cell patterning and cell arrays. Enhanced adhesion of bacteria on micro-nanotextured surfaces (of ∼12 μm roughness height) can be exploited in efficient bacteria capturing on such surfaces before their detection (Kastania et al., 2017).

Micro nanostructured (via ultrafast laser processing) surfaces (roughness ratio of 1.6) have been of interest also in tissue engineering, where the flow-induced shear stress in combination with surface topography have been shown to inhibit differentiation of Neuro-2a cells (Babaliari et al., 2025). Micro-nanotextured surfaces (with hierarchical topography of mean height ∼800 nm) were also found appropriate for selective proliferation and enrichment (25–80x) of cancer cells with respect to normal ones (Kanioura et al., 2020). The enhanced cell-surface interaction of cancer cells combined with the slower translocation of such cells (240 μs on surfaces with Ra = 519 nm) vs. smooth ones (149 μs, Ra = 20 nm) was applied to the detection of circulating cancer cells in blood (Islam et al., 2015a). Cancer cells were also captured on aptamer functionalized nanotextured surfaces (roughness of 500 nm) for their efficient detection (83%) from blood (Islam et al., 2016). In addition, enhanced capturing (by 71% ± 19%) of cancer cells on antibody functionalized nanotextured surfaces (Rq∼680 nm) with respect to flat surfaces was used for the assessment of cells in post-capture analysis and efficient nucleic acid isolation process (Hasan et al., 2018).

In summary, the enhanced surface area of micro-nanotextured microfluidics has been exploited in enhanced adhesion of bacteria, normal and cancer cells for applications in bacteria detection, tissue engineering, enrichment and detection of cancer cells.

2.2.5 Biocidal action

In many applications, such as point-of-care diagnostics for rapid detection of pathogens, bacterial lysis is required as an important on-chip step, followed by nucleic acid amplification and detection. For this reason, bactericidal action demonstrated for a variety of surfaces was also implemented in microfluidics to allow reagent-free bacterial lysis and on-chip integration of all processing steps for DNA-based detection of bacteria. To this end, black-Si nanospikes ∼500 nm high and 95 nm in diameter (Wang et al., 2016) as well as ZnO nanospikes several μm in length and 130–400 nm in diameter (Xesfyngi et al., 2023) have been used for bacterial cell lysis and DNA release for subsequent processing and analysis, as well as for rapid disinfection of bacteria-containing solutions. In addition, electrical lysis devices have been implemented, where multi-scale (micro-nanotextured) electrodes lower the voltage (from 8 to 4 V) needed for electrical bacterial lysis and enhance the lysis efficiency to 100% (Gabardo et al., 2015b). Successful extraction of nucleic acids from bacterial samples processed in devices bearing biocidal action demonstrates the potential for these devices to be integrated within practical lab-on-a-chip systems.

Summarizing, textured surfaces of proper (usually nanospike) geometry (few 100’s nm in diameter and few μm in length) have been implemented in microfluidics and LoC devices for their biocidal action, for application in reagent-free bacterial cell lysis and DNA release for subsequent analysis, as well as in rapid decontamination of liquid samples from bacteria.

3 Commercialization potential

Despite the tremendous progress achieved during the last 35 years in microfluidics and LoC technology and the numerous prototypes realized for improvements in research and applications, the commercialization of microfluidics still faces significant challenges, primarily driven by the lack of high-volume manufacturing and standardization (e.g., interfaces), the high manufacturing costs (e.g., molding), and the hurdles in system integration (e.g., external, bulky equipment). The same is undeniable for micro-nanotextured microfluidics; despite that they can be utilized in a plethora of fields from the biomedical and life science industry to environmental monitoring, food-safety, and microfluidics-based wearables and microheat-exchangers, the utilization of the micro-nanotexturing effect and its broader commercialization is so far limited, probably due to the difficulty of bridging the gap between laboratory prototypes and mass production.

It is the authors’ opinion that especially plasma micro-nanotexturing addresses the main hurdle of high-volume manufacturing, due to the wide implementation of plasma processing in the semiconductor and electronics industries. In addition, plasma micro-nanotexturing is rather generic in a great variety of polymeric substrates implemented for microfluidics fabrication, and is more environmentally friendly compared to wet processing due to less waste disposal. Nanoplasmas P.C. (https://www.nanoplasmas.com/en/), a specialized spin-off of NCSR “Demokritos”, commercializes plasma nanotextured microfluidics for passive SH valving, as well as rapid and sensitive bacteria detection in water (Tsougeni et al., 2024).

However, there are still many technological problems to be overcome concerning plasma micro-nanotexturing. Plasma reactors, which produce fast, uniform, and reproducible texturing over large areas, need to be commercialized. In addition, a major challenge is to make all walls of a microfluidic device possess the same functionality, if crucial for the device operation. The ability to bond a rough microfluidic channel and a rough lid with the same topography and chemical functionality might solve the problem. However, no reliable bonding technologies exist, which would make this feasible. Therefore, bonding technologies for sealing microfluidics need to be further developed, to avoid destroying chemical functionality or micro-nanostructures.

Another company, Achira Labs Ltd., (https://achiralabs.com/#page-about), faces the hurdle of high-volume microfluidics manufacturing by the utilization of porous, textile-based microfluidics combining the mimicry of capillary networks for the passive manipulation of liquids (Choudhary, 2017) with the inherent scalability of the textile manufacturing process, leading to significant cost savings.

To conclude, the microfluidics industry and specifically that of micro-nanotextured microfluidics needs to overcome significant engineering and logistical hurdles to achieve widespread commercial success.

4 Conclusion and outlook

Although surface roughness is traditionally undesirable in device fabrication, it has been shown to be useful and even advantageous in many cases in the field of microfluidics. In this review, a variety of fabrication methods for the creation of microchannel walls of tunable hierarchical roughness were presented and the enhanced functional properties imparted by roughness to such devices and their exploitation in a wide range of applications were discussed.

The intentional incorporation of micro-nanotextured surfaces in microfluidics and LoC devices provides several benefits stemming from their enhanced surface area which, in combination with appropriate surface chemistry, leads to tunable wettability and control over fluid behavior and transport, as well as on biological interactions in microfluidic channels. Exploiting wettability control, especially at its extremes, facilitates operation of microfluidics either by reducing the drug and pressure drop in the case of superhydrophobic microchannels, or by providing passive valves with tunable opening pressure within superhydrophilic channels. By its own, the enhanced surface area of microfluidic walls has been exploited in enhanced immobilization of biomolecules, allowing the creation of sensors and analytical devices with superior sensitivity to the detection of target molecules. In addition, the enhanced surface area of micro-nanotextured surfaces is found to lead to improved cell-to-surface adhesion over smooth surfaces, with application in the realization of sensitive bacteria-based sensors and bacteria capturing devices with increased capture efficiency, as well as in selective proliferation and enrichment of rare cells (e.g., cancer cells) with respect to normal ones. Last but not least, nanorough surfaces of spike-like geometry are shown to enable reagent-free bacterial cell lysis and rapid disinfection of bacteria-containing solutions.

It is believed that the above-mentioned unique enhanced properties of microfluidic and sensor devices, due to the incorporation of micro-nanotextured surfaces, may be combined in the future to create novel, “smart” (multifunctional) passive, and high performance, intelligent platforms that enable fluid manipulation with minimal external actuators. In addition, these surfaces may be moving towards organ-on-chip technologies, by improving 3D cell culture models by mimicking the physiological microenvironment and facilitating better cell adhesion and differentiation. However, as the industry is moving from laboratory-scale prototyping to industrial-scale manufacturing, a major focus of future research is improving the robustness of micro-nanotextured microfluidics to withstand high pressures, in addition to moving toward new, biocompatible materials, for more accurate on-chip biomedical diagnostics.

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Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/frlct.2026.1820279/full#supplementary-material

Supplementary material Supplementary material at the source

Footnotes

Edited by: Nan Zhang, University College Dublin, Ireland

Reviewed by: Tianyu Guan, University College Dublin, Ireland

Xinhui Wang, Southwest Jiaotong University, China

Statements

Conflict of interest

Authors EG and AT are co-founders of Nanoplasmas P.C. The remaining author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The author AT declared that they were an editorial board member of Frontiers at the time of submission. This had no impact on the peer review process and the final decision.

Funding

The author(s) declared that financial support was received for this work and/or its publication. This work was supported by the EU Horizon project VortexLC (“Vortex enhanced liquid chromatography for HbA1c monitoring based diabetes management in a globalized setting”, contract No 101047029, www.vortexlc.com).

Author contributions

AK: Conceptualization, Data curation, Formal Analysis, Writing – original draft, Writing – review and editing. EG: Funding acquisition, Resources, Writing – review and editing. AT: Conceptualization, Data curation, Formal Analysis, Writing – original draft, Writing – review and editing.

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Citation

Kastania, A. S., et al. (2026). The added value of micro-nanotextured surfaces integrated in microfluidics and lab-on-a-chip. Frontiers in Lab on a Chip Technologies, Volume 5. https://doi.org/
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Copyright © 2026 Kastania, Gogolides and Tserepi.

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*Correspondence: Angeliki Tserepi

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