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We report a cell recognition chromatography approach for blood cancer cell separation from healthy peripheral blood mononuclear cells (PBMCs) based on size-matched functionalized particle imprints. Negative imprints were prepared from layers of 15 μm polymeric microbeads closely matching the size of cultured human leukemic cells (HL60). We replicated these imprints on a large scale with UV curable polyurethane resin using nanoimprinting lithography. The imprints were functionalized with branched polyethylene imine (bPEI) and passivated by Poloxamer 407 to promote a weak attraction toward cells. When a matching cell fits into an imprint cavity, its contact area with the imprint is maximized, which amplifies the attraction and the binding selectivity. We tested these imprints specificity for depleting myeloblasts from a mixture with healthy human PBMCs in a cell recognition chromatography setup hosting the imprint. The mixture of fixed HL60/PBMCs ratio was circulated over the imprint and at each step the selectivity toward HL60 was assessed by flow cytometry. The role of the imprint length, flow rate, channel depth, and the bPEI coating concentration were examined. The results show that HL60 cells, closely matching the imprint cavities, get trapped on the imprint, while the smaller PBMCs are carried away by the drag force of the flow. Lower flow rates, longer imprints, and interim channel depth favor HL60 specific retention. The bPEI concentration higher than 1 wt % on the imprint made it less selective toward the HL60 because of indiscriminate attraction with all cells. Particle imprint based cell recognition chromatography was able to achieve selective myeloblast depletion from initial 11.7% HL60 (88.3% PBMC) to less than 1.3% HL60 for 3 h of circulation. The cell recognition chromatography with size-matched microbead imprints can be employed as an efficient cell separation technique and potentially lead to alternative therapies for myeloblasts removal from peripheral blood of patients with acute myeloid leukemia.

We report a new approach for separation of blood cancer cells from healthy white blood cells based on cell recognition by surface functionalised particle imprints. We prepared polymeric particle imprints from a layer of suspension of monodisperse PMMA microbeads which closely match the size of in vitro cultured human leukaemia cells (HL60). The imprints were replicated on a large scale with UV curable polyurethane resin using nanoimprinting lithography and surface functionalized with a cationic polymer, a branched polyethylene imine (bPEI), and a Pluronic surfactant, Poloxamer 407, to engineer a weak attraction towards the cells. The latter is amplified several orders of magnitude when a cell of a closely matching size and shape fits into the imprint cavity which multiplies the contact area between the cell surface and the imprint. The particle imprints were optimised for their specificity toward blood cancer cells by treatment with oxygen plasma and then subsequent coatings with bPEI and Poloxamer 407 with various functionalisation concentrations. We tested the surface functionalised imprints for their specificity in retaining in vitro cultured human leukaemic cells (HL60) over healthy human peripheral blood mononuclear cells (PBMCs) in a flow through chamber. The effect of the flushing flow rate of the mixed cell suspension over the particle imprint and the imprint length were also investigated. At each step the selectivity towards HL60 was assessed. Selective isolation of an increased amount of HL60 tumour cells over PBMC was ultimately achieved as a function of the cell seeding ratio on the particle imprint. The effect is attributed to the substantial size difference between the HL60 cell and the PBMCs. The data presented show that relatively inexpensive PMMA microbeads imprints can be utilised as a cell separation technique which could ultimately lead to novel therapies for removal of neoplastic cells from the peripheral blood of acute myeloid leukaemia patients.

The nanoimprint replication of biomimetic nanostructures can be interesting for a wide range of applications. We demonstrate the process chain for Morpho-blue-inspired nanostructures, which are especially challenging for the nanoimprint process, since they consist of multilayer undercut structures, which typically cannot be replicated using nanoimprint lithography. To achieve this, we used a specially made, proprietary imprint material to firstly allow successful stamp fabrication from an undercut master structure, and secondly to enable UV-based nanoimprinting using the same material. Nanoimprinting was performed on polymer substrates with stamps on polymer backplanes to be compatible with roller-based imprinting processes. We started with single layer undercut structures to finally show that it is possible to successfully replicate a multilayer undercut stamp from a multilayer undercut master and use this stamp to obtain multilayer undercut nanoimprinted samples.

We report a large scale preparation of bioimprints of layers of cultured human leukemic HL60 cells which can perform cell shape and size recognition from a mixture with peripheral blood mononuclear cells (PBMCs). We demonstrate that the bioimprint-cell attraction combined with surface modification and flow rate control allows depletion of the HL60 cells from peripheral blood which can be used for development of alternative therapies of acute myeloid leukaemia (AML).

Roll-to-roll UV nanoimprint lithography has superior advantages for high-throughput manufacturing of micro- or nano-structures on flexible polymer foils with various geometries and configurations. Our pilot line provides large-scale structure imprinting for cost-effective polymer biochips (4500 biochips/hour), enabling rapid and multiplexed detections. A complete high-volume process chain of the technology for producing structures like μ-sized, triangular optical out-couplers or capillary channels (width: from 1 μm to 2 mm, height: from 200 nm up to 100 μm) to obtain biochips (width: 25 mm, length: 75 mm, height: 100 μm to 1.5 mm) was described. The imprinting process was performed with custom-developed resins on polymer foils with resin thicknesses ranging between 125–190 μm. The produced chips were tested in a commercial point-of-care diagnostic system for multiplexed DNA analysis of methicillin resistant Staphylococcus aureus (e.g., mecA, mecC gene detections). Specific target DNA capturing was based on hybridisation between surface bound DNA probes and biotinylated targets from the sample. The immobilised biotinylated targets subsequently bind streptavidin–horseradish peroxidase conjugates, which in turn generate light upon incubation with a chemiluminescent substrate. To enhance the light out-coupling thus to improve the system performance, optical structures were integrated into the design. The limits-of-detection of mecA (25 bp) for chips with and without structures were calculated as 0.06 and 0.07 μM, respectively. Further, foil-based chips with fluidic channels were DNA functionalised in our roll-to-roll micro-array spotter following the imprinting. This straightforward approach of sequential imprinting and multiplexed DNA functionalisation on a single foil was also realised for the first time. The corresponding foil-based chips were able to detect mecA gene DNA sequences down to a 0.25 μM concentration. This research was supported by R2R BIOFLUIDICS project (http://www.r2r-biofluidics.eu/) under Horizon 2020 European Union (EU) Research and Innovation Programme with grant agreement no 646260. The research was also partially supported by NextGenMicrofluidics project (https:// www. nextgenmicrofluidics.eu/) under HORIZON2020 with grant agreement no 862092. The authors cordially thank Gerburg Schider & Gerhard Mohr, Markus Postl, Paul Patter and Alexander Wheeldon (JOANNEUM RESEARCH – Materials, Weiz, Austria) for revising the manuscript, preparing all the chip and R2R pilot line illustrations, taking the photographs and providing technical support, respectively. The authors are also grateful to Christian Wolf and Johannes Götz (JOANNEUM RESEARCH – Materials, Weiz, Austria) for their supports in the fluidic design and R2R UV-NIL structuring, respectively. We further kindly thank Alba Simon Munoz and Robert Fay (SCIENION AG, Berlin, Germany) for providing the illustration of the R2R micro-spotting line. PT specially thanks Ege Ozgun (NANOTAM, Bilkent University, Ankara, Turkey) for critically reading the manuscript.

Top-down fabrication of nanostructures with high throughput is still a challenge. We demonstrate the fast (10 m/min) and continuous fabrication of multilength scale structures by roll-to-roll UV-nanoimprint lithography on a 250 mm wide web. The large-area nanopatterning is enabled by a multicomponent UV-curable resist system (JRcure) with viscous, mechanical, and surface properties that are tunable over a wide range to either allow for usage as polymer stamp material or as imprint resist. The adjustable elasticity and surface chemistry of the resist system enable multistep self-replication of structured resist layers. Decisive for defect-free UV-nanoimprinting in roll-to-roll is the minimization of the surface energies of stamp and resist, and the stepwise reduction of the stiffness from one layer to the next is essential for optimizing the reproduction fidelity especially for nanoscale features. Accordingly, we demonstrate the continuous replication of 3D nanostructures and the high-throughput fabrication of multilength scale resist structures resulting in flexible polyethylenetherephtalate film rolls with superhydrophobic properties. Moreover, a water-soluble UV-imprint resist (JRlift) is introduced that enables residue-free nanoimprinting in roll-to-roll. Thereby we could demonstrate high-throughput fabrication of metallic patterns with only 200 nm line width.

Flexible composite stamps are commonly used in low pressure and low temperature processes, e.g., UV-assisted nanoimprint, as they provide a good conformal contact between stamp and substrate. The composite stamps investigated here consist of two layers, a thin hard top layer to enable stable nanometre-scaled structures with high aspect ratio and a soft backplane to ensure conformal contact. Stamps with two different material combinations were investigated, OrmoStamp /PDMS (polydimethylsiloxane) and h-PUA/s-PUA (polyurethane acrylate). The stability of both composite stamps was tested under harsh imprint conditions in a process at elevated temperature and pressure. Temperature and pressure loading results in strain in the top layer and may lead to break when the tensile strength is exceeded. To vary the stress level in the top layer, two different stamp designs were investigated, one with a thin backplane and one with a thicker backplane. The experimental results clearly show that a thin stamp (low stress level) is more stable than a thick stamp. Moreover, composite stamps are also suitable for a thermal imprint process when temperature and pressure remain limited.

Roll-to-roll UV nanoimprint lithography (R2R-UV-NIL) gains increasing industrial interest for large-area nano- and microstructuring of flexible substrates. It combines the possibility of multi length scale and 2.5D patterning of a functional resist with a square meter per minute productivity. The fabrication of micro- and nanooptic elements and systems nowadays can be named a classical application of batch NIL. However, large-area application fields like display, photovoltaics or solar cell markets ask for upscaling possibilities with respect to active area and throughput. The combination of direct laser lithography, step+repeat imprinting for shim fabrication and R2R reproduction even offers a much higher diversity of application fields. Free form lenses and mirrors, waveguiding units or complex light manipulating systems add new possibilities for customized photonic systems, security features or large area high-end decoration. Within this talk we will present the possibilities of combining greyscale laser lithography and roller-based imprinting with functionalized high-k imprint resins and see how to produce meters-per-minute 2.5D optical features on flexible substrates.

Roll-to-Roll-UV-nanoimprint lithography (R2R-UV-NIL) enables high resolution large area patterning of flexible substrates and is therefore of increasing industrial interest. We have set up a custom-made R2R-UV-NIL pilot machine which is able to convert 10 inch wide web with velocities of up to 30 m/min. In addition, we have developed self-replicable UV-curable resins with tunable surface energy and Young’s modulus for UV-imprint material as well as for polymer working stamp/shim manufacturing. Now we have designed test patterns for the evaluation of the impact of structure shape, critical dimension, pitch, depth, side wall angle and orientation relative to the web movement onto the imprint fidelity and working shim life time. We have used female (recessed structures) silicon masters of that design with critical dimensions between CD = 200 nm and 1600 nm, and structure depths of d = 500 nm and 1000 nm - all with vertical as well as inclined side walls. These entire master patterns have been transferred onto single male (protruding structures) R2R polymer working shims. The polymer working shims have been used for R2R-UV-NIL runs of several hundred meters and the imprint fidelity and process stability of the various test patterns have been compared. This study is intended as a first step towards establishing of design rules and developing of nanoimprint proximity correction strategies for industrial R2R-UV-NIL processes using polymer working shims.

The high throughput and large area nanostructuring of flexible substrates by continuous roller processes has great potential for future custom applications like wire grid polarizers, antireflection films, or super-hydrophobic surfaces. For each application different material characteristics have to be considered, e.g. refractive index, hydrophobicity, or dry etch stability. Herein, we show experimental results of nanoimprint lithography resist developments focused on inkjetable and photo-curable resists suitable for high throughput production, especially roll-to-roll NIL. The inkjet deposition of the novel materials is demonstrated by the use of different state-of-the-art inkjet printheads at room temperature. A plate-to-plate process on silicon substrates was successfully implemented on a NPS300 nano patterning stepper with previously inkjet dispensed NIL resist. Furthermore, we demonstrate a throughput of 30 m min-1 in a roller NIL process on PET. Dry etching of unstructured thin films on Si wafers was performed, and it was demonstrated that the etch stability in Si is tunable to a value of 3.5:1 by a concise selection of the resist components. The surface roughness of the etched films was measured to be < 2 nm, after etching of around 100 nm of the resist films what is an essential factor for a low line edge roughness. All resists reported herein can be deposited via inkjet dispensing at room temperature, are suitable for continuous high throughput imprinting on flexible substrates, and are applicable in step-wise NIL processes with good etch resistance in dry etch processes.

We report a study of the compression of monolayers of monodisperse spherical polystyrene particles at the interface between aqueous surfactant solutions and octane. The particle size (2.6 μm diameter) was selected so that direct in situ microscopic observation of the monolayer structure could be made during lateral compression and “collapse”. Monolayers have been formed on a miniature Langmuir trough placed on a microscope stage. Our study has focused on (a) the relationship between the monolayer collapse pressure, Πcol, and the interfacial tension, γ*, of the oil/water interface in the absence of a particle monolayer and (b) the mode of monolayer “collapse” at high surface pressure. Interfacial tensions γ* have been adjusted (in the range 50−4 mN m-1) by addition of surfactants over a range of concentration. We find that the monolayer collapses by buckling (folding) when the surface pressure is equal to the surface tension of the oil/water interface. Particle promotion out of the interface is not observe...

We have studied the compression and structure of compressed monolayers of sulfate polystyrene latex particles on air/water and octane/water interfaces. If compressed sufficiently (on a Langmuir trough) the monolayers at air/water surfaces give rafts of hexagonally packed particles, while those at oil/water interfaces undergo a transition from the originally hexagonal to a rhombohedral structure. We have found that beyond collapse the particle monolayers on both air/water and octane/water interfaces fold and corrugate, and there is no expulsion of individual particles or particle aggregates from the interface. In the case of air/water interfaces, the structuring of particle monolayers (below collapse) was found to be very sensitive to the electrolyte concentration in the aqueous phase. At low electrolyte concentration, a fairly ordered structure resulting from the interparticle repulsion was observed, while at high electrolyte concentration, the particles form 2D clusters. In marked contrast, particle mono...

Line tension is the excess energy associated with unit length of a three-phase contact line and it has long been of interest, in part because if sufficiently large, it can affect various processes of industrial and biological importance. Most recently, interest has centred on the magnitude and sign of experimentally determined values. Reported line tensions in systems with liquid alkanes in contact with aqueous phases include values from about +10−10 to 10−9 N on the one hand, and −10−6 N on the other. If the actual values of line tension lie close to the lower end of the spectrum quoted above, the influence on many systems of interest will be negligible. The higher values, however, could lead to pronounced effects. A study to determine line tension in the three-phase contact line around lenses of dodecane resting on a water subphase is presented. The method involves measuring, by interferometry, the variation of lens angle with the contact line radius. In order to bring the angles into a convenient range for measurement (around 2°), small amounts of dodecanol (ca. 2 mmol dm−3) have been added to the dodecane. The line tension is found to be +1.6±0.3×10−11 N. The magnitude and sign of the line tension is discussed in terms of surface forces.

Graphical abstractDisplay Omitted R2R-NIL is presented with high throughput roller speeds of 30mmin-1 and good pattern fidelity.The viscosity of the novel materials is below 20mPas, enabling inkjet dispensing at room temperature.Throughput variation from 1mmin-1 to 20mmin-1 decreased double bond conversion less than 5%. We report two newly developed photo-curable resists specifically engineered for inkjet dispensing facilitating nanoimprint lithography (NIL) in a high-throughput environment. The viscosity of the novel NIL resists was adjusted especially to enable inkjet dispensing at room temperature. The novel resists can be applied either in NIL batch processes or in high throughput processes like roll-to-roll NIL (R2R-NIL). Batch-wise imprints were performed on various substrates as Si or plastics demonstrating the distinctive application versatility of the novel materials. The very fast curing speed of these materials is discussed in detail with the aid of FT-IR and photo-DSC measurements. The experiments demonstrate a high degree of double bond conversion of about 80% after curing and a fast curing in a few seconds even at a low radiation intensity of 0.2mWcm-2. The novel materials show excellent adhesion on different substrates and high optical transparency. The high throughput capability of the novel materials is demonstrated by R2R-NIL processes performed at a web speed of up to 30mmin-1.

We report on our development strategy of photo-curable resists for nanoimprint lithography (NIL) based on modularity. Starting with a basic formulation, we address two topics: the integration of fluorinated additives and the enhancement of the dry etching stability. We prove both concepts by the introduction of two different resists derived from the same basic formulation. The viscosity of the novel resist materials was optimized for inkjet dispensing at room temperature (RT). The novel resist materials can be applied either in NIL batch processes or in high-throughput roller processes. Batch-wise imprints were performed on various substrates such as Si or plastics, demonstrating the distinctive application versatility of the novel materials. Dry etching of spincoated thin films on Si wafers was performed, demonstrating an etch stability versus Si of 3.5:1 by using the resist formulation with improved etching stability. Roll-to-roll NIL at high throughput on large areas was performed with web speeds of up to 30 mmin−1 with different stamp materials. We conclude that all resists reported herein can be deposited via inkjet dispensing at RT, are suitable for continuous high-throughput imprinting on flexible substrates, and are applicable in step-wise NIL processes with good etch resistance in dry etch processes.

The NILaustria research project cluster consists of 8 individual research projects and aims to improve nanoimprint lithography in an application driven approach. The cluster is presented as well as highlights from the projects, e.g. the replication of 12.5nm half pitch features using working stamp copies, topics from organic electronics, metamaterials and SiGe technology. An outlook on the new activities is given.

Light induced phase transitions were found in lyotropic liquid crystalline systems of aqueous cetyltrimethylammonium bromide (CTAB) and of Aerosol-OT (AOT)/decane/water: the isothermal transitions isotropic → nematic and isotropic → hexagonal in CTAB systems were triggered by the photocyclization of a solubilized naphthyl vinyl ether, the transition isotropic → inverse-hexagonal in the ternary AOT system was introduced by the trans-cis photoisomerization of a solubilized stilbazolium salt

There is currently considerable interest in the measurement of line tension. A method has been proposed involving capillary condensation of vapour around the contact (or near contact) of a solid sphere and a flat plate of the same material. This configuration is locally equivalent to that used in the conventional surface force apparatus (SFA), which employs (coated) mica surfaces that are molecularly smooth.

Generally, the potential impact of systematical overlay errors on 300mm wafers is much larger than on 200mm wafers. Process problems which are merely identified as minor edge yield detractors on 200mm wafers, can evolve as major roadblocks for 300mm lithography. Therefore, it is commonly believed that achieving product overlay specifications on 300mm wafers is much more difficult than on 200mm wafers. Based on recent results on high volume 300mm DRAM manufacturing, it is shown that in reality this assumption does not hold. By optimizing the process, overlay results can be achieved which are comparable to the 200mm reference process. However, the influence of non-lithographic processes on the overlay performance becomes much more critical. Based on examples for specific overlay signatures, the influence of several processes on the overlay characteristics of 300mm wafers is demonstrated. Thus, process setup and process changes need to be analyzed monitored much more carefully. Any process variations affecting wafer related overlay have to be observed carefully. Fast reaction times are critical to avoid major yield loss. As the semiconductor industry converts to 300mm technology, lithographers have to focus more than ever on process integration aspects.

Microemulsions composed of Aerosol OT (AOT), isooctane, and water in the mass ratio 1 :1.54 :0.75 exhibit percolation, i.e., transition from a w/o to an o/w microemulsion, at 33 °C as revealed by the appearance of conductivity. In the presence of 0.01 mol/dm 3 of acridizinium bromide the percolation temperature increases to 38 °C. Irradiation of this mixture with glass-filtered light leads to a further rise of the percolation temperature to 43 °C. Thus, the system can be switched from conducting to non-conducting upon irradiation at between 38 and 43 °C.

With the Covid-19-based global pandemic that started in the beginning of 2020, the vital importance of accelerated, reliable and affordable virus testing systems has once again become clearer. Besides, we all learned very well that the disposable biochips, to be used in these in vitro diagnostic (IVD) testing systems, supposed to be produced in large amounts in a very short time to be widely available for the use of humanity to save more and more lives. That is why; roll-to-roll (R2R) polymer structuring manners offer such large quantities for the production of in vitro biochips. Our technology, based on R2R UV nanoimprint lithography (UV-NIL), has superior features. Via our pilot line, robust 7500 biochip components per 100 meter of a flexible, polymer foil coated with a UV curable photo-resin (i.e., parts with capillary fluidic channels or optical structures for IVDs) can be generated. This study shows an example of a prototype of a R2R UV-NIL generated chip: a foil, capillary flow-based IVD biochip for multiplexed DNA detection purposes (i.e., a Lab-on-a-Foil device). The biochip performance was further increased dramatically by integrating UV-NIL produced retro-reflective microstructures, which reflects the light back, to its design to enhance optical signal detection in a commercial IVD device, detecting DNA on a chemiluminescent-reaction basis. Graphic Abstract

R2R-UV-nanoimprinting sets new benchmarks for the fabrication of miniaturized, low-cost and low-weight freeform micro-optical elements applicable in lighting, display, medical diagnostics, etc. We demonstrate the related process chain, combining optical design, direct laser lithography, step&repeat imprinting and R2R reproduction.