Rapid Prototyping of Organ-on-a-Chip Devices Using Maskless Photolithography

Organ-on-a-chip (OoC) and microfluidic devices are conventionally produced using microfabrication procedures that require cleanrooms, silicon wafers, and photomasks. The prototyping stage often requires multiple iterations of design steps. A simplified prototyping process could therefore offer major advantages. Here, we describe a rapid and cleanroom-free microfabrication method using maskless photolithography. The approach utilizes a commercial digital micromirror device (DMD)-based setup using 375 nm UV light for backside exposure of an epoxy-based negative photoresist (SU-8) on glass coverslips. We show that microstructures of various geometries and dimensions, microgrooves, and microchannels of different heights can be fabricated. New SU-8 molds and soft lithography-based polydimethylsiloxane (PDMS) chips can thus be produced within hours. We further show that backside UV exposure and grayscale photolithography allow structures of different heights or structures with height gradients to be developed using a single-step fabrication process. Using this approach: (1) digital photomasks can be designed, projected, and quickly adjusted if needed; and (2) SU-8 molds can be fabricated without cleanroom availability, which in turn (3) reduces microfabrication time and costs and (4) expedites prototyping of new OoC devices.

A rapid-prototyped moulding system towards optimised scalable fabrication of elastomeric microfluidic devices

3D printing and makerspace technologies are increasingly explored as alternative techniques to soft lithography for making microfluidic devices, and for their potential to segue towards scalable commercial fabrication. Here we considered the optimal application of current benchtop 3D printing for microfluidic device fabrication through the lens of lean manufacturing and present a straightforward but robust rapid prototyped moulding system that enables easy estimation of more precise quantities of polydimethylsiloxane (PDMS) required per device to reduce waste and importantly, making devices with better defined depths and volumes for (i) modelling gas exchange and (ii) fabrication consistency as required for quality-controlled production. We demonstrate that this low-cost moulding step can enable a 40 – 300% reduction in the amount of PDMS required for making individual devices compared to the established method of curing approximately 30 grams of PDMS prepolymer overlaid on a 4” silicon wafer master in a standard plastic petri dish. Other process optimisation techniques were also investigated and are recommended as readily implementable changes to current laboratory and foundry-level microfluidic device fabrication protocols for making devices either out of PDMS or other elastomers. Simple calculators are provided as a step towards more streamlined, software controlled and automated design-to-fabrication workflows for both custom and scalable lean manufacturing of microfluidic devices.

A rapid-prototyped moulding system towards optimised scalable fabrication of elastomeric microfluidic devices

3D printing and makerspace technologies are increasingly explored as alternative techniques to soft lithography for making microfluidic devices, and for their potential to segue towards scalable commercial fabrication. Here we considered the optimal application of current benchtop 3D printing for microfluidic device fabrication through the lens of lean manufacturing and present a straightforward but robust rapid prototyped moulding system that enables easy estimation of more precise quantities of polydimethylsiloxane (PDMS) required per device to reduce waste and importantly, making devices with better defined depths and volumes for (i) modelling gas exchange and (ii) fabrication consistency as required for quality-controlled production. We demonstrate that this low-cost moulding step can enable a 40 – 300% reduction in the amount of PDMS required for making individual devices compared to the established method of curing approximately 30 grams of PDMS prepolymer overlaid on a 4” silicon wafer master in a standard plastic petri dish. Other process optimisation techniques were also investigated and are recommended as readily implementable changes to current laboratory and foundry-level microfluidic device fabrication protocols for making devices either out of PDMS or other elastomers. Simple calculators are provided as a step towards more streamlined, software controlled and automated design-to-fabrication workflows for both custom and scalable lean manufacturing of microfluidic devices.

Properties and Applications of PDMS for Biomedical Engineering: A Review

Polydimethylsiloxane (PDMS) is an elastomer with excellent optical, electrical and mechanical properties, which makes it well-suited for several engineering applications. Due to its biocompatibility, PDMS is widely used for biomedical purposes. This widespread use has also led to the massification of the soft-lithography technique, introduced for facilitating the rapid prototyping of micro and nanostructures using elastomeric materials, most notably PDMS. This technique has allowed advances in microfluidic, electronic and biomedical fields. In this review, an overview of the properties of PDMS and some of its commonly used treatments, aiming at the suitability to those fields’ needs, are presented. Applications such as microchips in the biomedical field, replication of cardiovascular flow and medical implants are also reviewed.

Conductive Bioimprint Using Soft Lithography Technique Based on PEDOT:PSS for Biosensing

Culture platform surface topography plays an important role in the regulation of biological cell behaviour. Understanding the mechanisms behind the roles of surface topography in cell response are central to many developments in a Lab on a Chip, medical implants and biosensors. In this work, we report on a novel development of a biocompatible conductive hydrogel (CH) made of poly (3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) and gelatin with bioimprinted surface features. The bioimprinted CH offers high conductivity, biocompatibility and high replication fidelity suitable for cell culture applications. The bioimprinted conductive hydrogel is developed to investigate biological cells’ response to their morphological footprint and study their growth, adhesion, cell–cell interactions and proliferation as a function of conductivity. Moreover, optimization of the conductive hydrogel mixture plays an important role in achieving high imprinting resolution and conductivity. The reason behind choosing a conducive hydrogel with high resolution surface bioimprints is to improve cell monitoring while mimicking cells’ natural physical environment. Bioimprints which are a 3D replication of cellular morphology have previously been shown to promote cell attachment, proliferation, differentiation and even cell response to drugs. The conductive substrate, on the other hand, enables cell impedance to be measured and monitored, which is indicative of cell viability and spread. Two dimensional profiles of the cross section of a single cell taken via Atomic Force Microscopy (AFM) from the fixed cell on glass, and its replicas on polydimethylsiloxane (PDMS) and conductive hydrogel (CH) show unprecedented replication of cellular features with an average replication fidelity of more than 90%. Furthermore, crosslinking CH films demonstrated a significant increase in electrical conductivity from 10−6 S/cm to 1 S/cm. Conductive bioimprints can provide a suitable platform for biosensing applications and potentially for monitoring implant-tissue reactions in medical devices.

Fabrication of Perforated PDMS Microchannel by Successive Laser Pyrolysis

Poly(dimethylsiloxane) has attracted much attention in soft lithography and has also been preferred as a platform for a photochemical reaction, thanks to its outstanding characteristics including ease of use, nontoxicity, and high optical transmittance. However, the low stiffness of PDMS, an obvious advantage for soft lithography, is often treated as an obstacle in conducting precise handling or maintaining its structural integrity. For these reasons, a Glass-PDMS-Glass structure has emerged as a straightforward alternative. Nevertheless, several challenges are remaining in fabricating Glass-PDMS-Glass structure through the conventional PDMS patterning techniques such as photolithography and etching processes for master mold. The complicated techniques are not suitable for frequent design modifications in research-oriented fields, and fabrication of perforated PDMS is hard to achieve using mold replication. Herein, we utilize the successive laser pyrolysis technique to pattern thin-film PDMS for microfluidic applications. The direct use of thin film at the glass surface prevents the difficulties of thin-film handling. Through the precise control of photothermal pyrolysis phenomena, we provide a facile fabrication process for perforated PDMS microchannels. In the final demonstration, the laminar flow has been successfully created owing to the smooth surface profile. We envision further applications using rapid prototyping of the perforated PDMS microchannel.

Micromachined Tactile Sensor Array for RTSA

This work presents a polymer-based tactile capacitive sensor capable of measuring joint reaction forces of reverse total shoulder arthroplasty (RTSA). The capacitive sensor contains a polydimethylsiloxane (PDMS) dielectric layer with an array of electrodes. The sensor was designed in such a way that four components of glenohumeral contact forces can be quantified to help ensure proper soft tissue tensioning during the procedure. Fabricated using soft lithography, the sensor has a loading time of approximately 400 ms when a 14.13 kPa load is applied and has a sensitivity of 1.24 × 10−3 pF/kPa at a load of 1649 kPa. A replica RTSA prothesis was 3D printed, and the sensor was mounted inside the humeral cap. Four static right shoulder positions were tested, and the results provided an intuitive graphical description of the pressure distribution across four quadrants of the glenohumeral joint contact surface. It may help clinicians choose a right implant size and offset that best fit a patient’s anatomy and reduce postoperative biomechanical complications such as dislocation and stress fracture of the scapula.

2-photon-fabricated nano-fluidic traps for extended detection of single macromolecules and colloids in solution

The analysis of nanoscopic species, such as proteins and colloidal assemblies, at the single-molecule level has become vital in many areas of fundamental and applied research. Approaches to increase the detection timescales for single molecules in solution without immobilising them onto a substrate surface and applying external fields are much sought after. Here we present an easy-to-implement and versatile nanofluidics-based approach that enables increased observational-timescale analysis of single biomacromolecules and nanoscale colloids in solution. We use two-photon-based hybrid lithography in conjunction with soft lithography to fabricate nanofluidic devices with nano-trapping geometries down to 100 nm in height. We provide a rigorous description and characterisation of the fabrication route that enables the writing of nanoscopic 3D structures directly in photoresist and allows for the integration of nano-trapping and nano-channel geometries within micro-channel devices. Using confocal fluorescence burst detection, we validated the functionality of particle confinement in our nano-trap geometries through measurement of particle residence times. All species under study, including nanoscale colloids, α-synuclein oligomers, and double-stranded DNA, showed a three to five-fold increase in average residence time in the detection volume of nano-traps, due to the additional local steric confinement, in comparison to free space diffusion in a nearby micro-channel. Our approach thus opens-up the possibility for single-molecule studies at prolonged observational timescales to analyse and detect nanoparticles and protein assemblies in solution without the need for surface immobilisation.

Polycarbonate Masters for Soft Lithography

Fabrication of microfluidic devices by soft lithography is by far the most popular approach due to its simplicity and low cost. The approach relies on casting of elastomers, such as polydimethylsiloxane (PDMS), on masters fabricated from photoresists on silicon substrates. These masters, however, can be expensive, complicated to fabricate, and fragile. Here we describe an optimized replica molding approach to preserve the original masters by heat molding of polycarbonate (PC) sheets on PDMS molds. The process is faster and simpler than previously reported methods and does not result in a loss of resolution or aspect ratio for the features. The generated PC masters were used to successfully replicate a wide range of microfluidic devices, including rectangular channels with aspect ratios from 0.025 to 7.3, large area spiral channels, and micropost arrays with 5 µm spacing. Moreover, fabrication of rounded features, such as semi-spherical microwells, was possible and easy. Quantitative analysis of the replicated features showed variability of <2%. The approach is low cost, does not require cleanroom setting or hazardous chemicals, and is rapid and simple. The fabricated masters are rigid and survive numerous replication cycles. Moreover, damaged or missing masters can be easily replaced by reproduction from previously cast PDMS replicas. All of these advantages make the PC masters highly desirable for long-term preservation of soft lithography masters for microfluidic devices.

A Novel Fabricating Method of Micro Lens-on-Lens Arrays with Two Focal Lengths

Micro lens-on-lens array (MLLA) is a novel 3D structure with unique optical properties that cannot be fabricated accurately and quickly by existing processing methods. In this paper, a new fabricating method of MLLAs with two focal lengths is proposed. By introducing the soft lithography technology, nano-imprint technology and mask alignment exposure technology, MLLAs with high precisions can be obtained. A MLLA is successfully fabricated with two focal lengths of 58 μm and 344 μm, and an experiment is carried out. The results show that the MLLA has excellent two-level focusing and imaging abilities. Furthermore, the fabricated profiles of the MLLA agree well with the designed profiles, and the morphology deviation of the MLLA is better than 2%, satisfying the application requirements. The results verify the feasibility and validity of the novel fabricating method. By adjusting mask patterns and processing parameters, MLLAs with both changeable sizes and focal lengths can be obtained.