PDMS의 중합 억제와 Polyvinyl Chloride 패턴을 이용한 약물 전달 기기 공정 방법 제안

학위논문 (박사)-- 서울대학교 대학원 : 공과대학 전기·정보공학부, 2019. 2. 서종모.Effective drug therapy requires an adequate dosage control that can control the plasma concentration to be in between Maximum Tolerated Concentration (MTC) and Minimum Effective Concentration (MEC). The conventional drug administration methods fail to achieve effective drug therapy. Therefore, localized drug delivery devices have been devised to overcome the shortcomings of systemic drug administration, oral gavage and intravenous injection. Localized drug delivery devices realize spatial control simply by installing it on desired sites. Challenges of drug delivery devices are precise control of dosage, exact time of release, and low power consumption. All of these can be achieved by controlling the actuation components of the device: microvalves and pumps. The proposed device utilizes a balloon-like inflatable and deflatable drug reservoir, which eliminates the use of a pump. Moreover, a normally closed magnetically actuated microvalve that requires power consumption only when it opens was constructed. Consequently, the device was designed to release drug substances driven by the tension and stress formed by the inflated drug chamber only upon the actuation of the microvalve. Conventional PDMS patterning methods introduced in Micro Electromechanical Systems (MEMS) include photolithography and etching. Previous methods, however, require several steps and long processing time. A novel PDMS patterning method that only employs vapor deposition, oxygen plasma treatment, and stencil screen-printing was devised for simpler and faster procedure. Vapor deposition of trichlorosilane is a commonly used method to coat a barrier between PDMS layers from bonding. In the contrary, oxygen plasma treatment is a method used to bond layers of polymerized PDMS. Coordinating the two methods, along with a polyvinyl chloride (PVC) stencil patterned using a cutting plotter or a diode pumped solid-state laser, selective bonding was implemented. Selective bonding of PDMS accounted for the formation of the drug reservoir and the pump. Moreover, inhibition of PDMS polymerization was exploited over PVC substrates to acquire results similar to PDMS etching. This new etching alternative was used to construct microchannels with widths ranging from approximately 200 to 1000 micrometers. These microchannels with varying cross-sectional area served as a secondary drug release rate regulator. A magnetically actuated microvalve consist of two components. The opening mechanism of this normally closed valve was driven by an external magnet that produces magnetic field and a circular magnetic membrane with a neodymium magnet bonded on the surface with PDMS that deflects towards the external magnetic source. All the component of the microvalve were fabricated using only PVC stencils and PDMS-metal powder composites. Nickel powder-PDMS composite was used for the deflection membrane. The completed device was evaluated on biocompatibility for implantation and durability for reusability. PDMS may be biocompatible, PDMS-metal powder may show different results. In the device, even though PDMS-metal powder composites were encapsulated with pure PDMS, long-term use may increase cytotoxicity. Moreover, surface modification using trichlorosilane and oxygen plasma may also have an adverse effect on biocompatibility. Therefore, the device was tested for biocompatibility using elution and cell growth evaluation. Furthermore, the device was intended to be refillable and reusable. Thus, the durability of the microvalve and the inflatable chamber was evaluated by actuating the valve multiple times and whether or not the mechanical characteristic changed over the experiment.의료 분야의 발전에 따라 수많은 약들이 개발되어 왔지만 아직까지 투여 방법은 경구 투여 방법과 정맥에 바로 주입하는 주사기를 통한 방법으로만 지속되고 있다. 경구 투여와 정맥 주사는 투여 방법이 쉽다는 이유 때문에 아직도 주로 쓰이지만 특정 부위 또는 목표 세포에만 약물을 전달하는 것은 어렵다. 효율적인 약물 전달은 최소독성혈중농도 (MTC) 와 최소유효혈중농도 (MEC) 사이를 유지하도록 약물을 적정량 그리고 적정 기간을 두고 전달해야 한다. 현재에도 흔히 쓰이는 약물 전달 방식은 이러한 효율적인 약물 요법의 조건들을 만족하지 못한다. 그러므로 경구 투약이나 주사에 의한 투여 방법의 단점들을 보완할 수 있는 약물 전달 기기들이 활발히 연구되고 있다. 국소 부위에 설치하는 약물 전달 기기들은 약물 전달이 필요한 부위에 설치되는 방법으로 공간적인 제어를 실현한다. 이러한 전달 기기들이 만족해야 하는 조건들은 적정량의 약물, 정확한 시간에 그리고 저전력으로 구동이 가능해야 한다는 것이다. 이 모든 조건들은 대부분의 약물 전달 기기들이 가지고 있는 밸브와 펌프를 통해 달성할 수 있다. 본 논문에서 제안하는 약물 전달 기기는 풍선과 같이 부풀고 수축이 가능한 약물 저장소 구조를 제작하는 방법을 제안하여 전력이 필요한 펌프가 없이도 약물 전달이 가능하게 하였다. 이 펌프는 자기장 혹은 전자기장의 유무에 따라 구동되는 밸브를 만들어 약물 전달은 이 밸브를 열고 닫는 것만으로 가능하게 하였다. 이 밸브는 평상시에 닫혀 있는 형태로 열릴 때만 전력을 사용하여 전력 사용량을 최소화 하였다. 이 약물 전달 기기의 제작은 Polydimethylsiloxane (PDMS) 와 PDMS 와 금속 기반의 마이크로 입자의 합성물로만 이루어지도록 하였다. PDMS 패터닝은 일반적으로 Micro Electromechanical Systems (MEMS) 의 포토리소그래피 (photolithography) 와 식각 (etching) 방식을 통해 이루어진다. 하지만 이런 방식은 여러층과 복잡한 구조를 만들려면 여러 단계 그리고 긴 시간 동안의 공정 시간이 필요하다. 본 논문에서는 사진석판술이나 식각과 같은 결과를 낳을 수 있는 새로운 PDMS 공정 방법을 산소 플라즈마 표면처리 (oxygen plasma treatment), 자기조립분자막 (self-assembled monolayer) 그리고 폴리염화 비닐 시트지 패터닝을 사용해 약물 전달 기기 제작법을 제안한다. 자기조립분자막은 PDMS 와 PDMS 간의 접착이 이루어지지 않게 하기 위한 막을 분자 단위의 두께로 제작하는 방법이다. 반대로 산소 플라즈마 표면처리는 PDMS 간의 접착이 더 효과적으로 이루어지게 하는 방식이다. 자기조립분자막과 산소 플라즈마 표면처리를 조합하여 폴리염화비닐 패턴을 통해 선택적 표면 접착을 실행하였다. 폴리염화비닐 패턴은 칼로 잘라내는 자동 플로터 (blade plotter) 와 레이저로 잘라내는 다이오드 펌핑 고체 레이저 (diode pumped solid state laser) 두 기기로 제작하였다. 선택적 표면 접착 방법은 약물 저장소를 만드는데 사용하였다. 더 나아가, 폴리염화비닐과 PDMS 의 중합 억제 관련성을 조사하여 PDMS 식각을 실현하였다. PDMS 식각은 약물 저장소와 밸브를 연결하는 마이크로 채널을 만드는데 사용하였다. 이 약물 전달 기기의 약물 전달량은 기기의 약물 저장소의 크기, 막 두께, 저장소를 빠져나가는 마이크로 채널의 단면적 크기 등 복합적인 요소에 따라 달라진다. 약물 전달 시기를 제어하는 것은 자기장 또는 전자기장을 통해 구동되는 마이크로 밸브이다. 이 밸브는 저전력 구동이 가능하도록 평상시에는 닫혀 있도록 설계되었다. 약물의 전달 시기를 조절하는 밸브는 외부 자기장으로 구동 될 수 있도록 제작되었다. 이 밸브는 얇은 니켈 마이크로 입자와 PDMS로 섞은 얇은 막에 네오디뮴 자석이 접합되어 있어 평소에는 닫혀있는 상태를 유지하다 자기장으로 구동되어 당겨지는 힘에 의해 열리는 구조를 가지고 있다. 자기 구동은 막이 당겨지는 방향으로 자석을 위치시켜 밸브가 열리게 할 수 있다. 마지막으로, 제작된 약물 전달 기기는 생체 적합성을 분석하기 위해 용출물 실험과 세포 독성 실험을 진행하였다. PDMS는 높은 생체적합성을 가지는 물질로 판명된 물질이다. 하지만 PDMS만 쓰지 않고 금속 마이크로 입자를 섞은 PDMS와 네오디뮴 자석도 사용하였기에, 또 이 기기는 피부에 접합하여 사용하거나 약물이 전달되어야 하는 체내에 설치하는 방식으로 사용 되기 때문에 생체 적합성 실험을 진행하였다. 더 나아가, 이 기기의 중요한 구성 요소인 밸브와 펌프의 내구성도 조사되었다. 반복적인 실험으로 약물 전달량의 변화가 없는지 또는 밸브에서 누출이 이루어지지 않는지도 실험하였다.Table of Contents Abstract i Table of Contents iv List of Figures vii List of Tables x Chapter 1. Introduction 1 1.1 Drug Delivery Device in Microfluidics 2 1.2 Localized Drug Delivery Device 3 1.3 Microvalves and Pumps in Microfluidic Devices 5 1.4 Polydimethylsiloxane (PDMS) Etching 8 1.5 PDMS Surface Modification: Hydrophilic Alteration 10 1.6 Circular Cross-sectional Microchannels 12 1.7 Flexible Conductive PDMS 15 1.8 PDMS Adhesion 17 1.9 Previously Developed Drug Delivery Devices 19 1.9.1 Electro-actively Controlled Thin Film 19 1.9.2 Drug Release through Microchannel Configuration 20 1.9.3 Frequency Controlled Hydrogel Microvalve 21 1.9.4 Magentically Controlled MEMS Device 22 1.9.5 Electrochemical Intraocular Drug Delivery Device 23 1.9.6 Electrostatic Valve with Thermal Actuation 25 1.9.7 Transdermal Delivery through Microneedles 27 1.9.8 Osmotic Drug Delivery Devices 28 1.10 Summary 35 Chapter 2. Materials and Procedure 39 2.1 System Overview 39 2.2 Materials 41 2.2.1 Polydimethylsiloxane (PDMS) 41 2.2.2 Polyvinyl Chloride (PVC) Adhesive Sheets 42 2.2.3 Magnetic Microparticles and Neodymium Magnet 45 2.2.4 Silver Microparticles 46 2.3 Procedures 48 2.3.1 Spin Coating 48 2.3.2 Oxygen Plasma Treatment 49 2.3.3 Silanization (Self-Assembled Monolayer) 51 2.3.4 Plasma Bonding 53 2.4 Fabrication 54 2.4.1 PDMS Etching via PVC Stencils 54 2.4.2 Inflatable Chamber Fabrication 59 2.4.3 Full Fabrication of the Drug Delivery Device 63 2.4.3.1 Primary and Secondary Drug Chamber 64 2.4.3.2 Microvalve 67 2.4.3.3 Magnetic Actuation 71 Chapter 3. Results 74 3.1 PVC Stencil Preparation 74 3.2 Surface Modification and Selective Bonding 76 3.3 PDMS Polymerization Inhibition 83 3.4 PDMS Etching 86 3.5 Three Dimensional Microchannel Fabrication 91 3.6 Circular Cross-sectional Microchannel 94 3.7 Inflatable Chamber Fabrication 97 3.8 Conductive PDMS Fabrication 99 3.9 Drug Delivery Device 104 3.9.1 Dimensions and Profile of the Device 105 3.9.2 Fluid Release Amount of the Device 105 3.8.2.1 Case 1 105 3.9.2.2 Case 2 106 3.9.2.3 Case 3 107 3.10 In Vitro Cytotoxicity of the Device 110 Chapter 4. Discussion 116 4.1 Electromagnetic Actuation 116 4.2 Drug Substance Delivery 118 4.3 Comparison with Similar Drug Delivery Devices 119 4.4 Integration of the Device with PDMS Electrodes 121 Bibliography 123 Abstract in Korean 143Docto

RAPID-PROTOTYPING OF PDMS-BASED MICROFLUIDIC DEVICES

Microfluidics uses the manipulation of fluids in microchannels to accomplish innumerous goals, and is attractive to analytical chemistry because it can reduce the scale of larger analytical processes. The benefits of the use of microfluidic systems, in comparison with conventional processes, include efficient sample and reagent consumption, low power usage and portability. Most microfluidic applications require a development process based on iterative design and testing of multiple prototype microdevices. Typical microfabrication protocols, however, can require over a week of specialist time in high-maintenance cleanroom facilities, making the iterative process resource-intensive and prohibitive in many locations. Rapid prototyping techniques can alleviate these issues, enabling faster development of microfluidic structures at lower costs. Print-and-peel techniques (PAP), including wax printing and xurography, are low-cost fast-prototyping tools used to create master molds for polydimethylsiloxane (PDMS) miniaturized systems. In this work, three different methods were created to improve the rapid-prototyping of PDMS-based microfluidic devices. Using the wax printing method, PDMS microdevices can now be fabricated from design to testing in less than 1 hour, at the cost of $0.01 per mold, being one of the fastest and cheapest methods to date. If extensive fluidic manipulation is required, xurography becomes the method of choice. The xurography technique presented here is the most rapid tool to fabricate PDMS-based microdevices to date, presenting turnaround times as fast as 5 minutes. The first hybrid technique that can be used either as a PAP or a scaffolding method is also presented here, using the same materials and fabrication process. The green, low-cost, user-friendly elastomeric (GLUE) rapid prototyping method to fabricate PDMS-based devices uses white glue as the patterning material, and is capable of fabricating multi-height molds in a single step, improving even further the development of PDMS microfluidic devices. Device fabrication is only one of the steps in the iterative process of designing a fully-functional microfluidic tool. The design of the microdevice itself plays a crucial role in its performance, which directly impacts processes conducted in miniaturized devices. In this work, the influence of hydrodynamic resistance in sample dispersion on a microfluidic multiplexer was studied using paper-based analytical microfluidic devices (µPADs) as the testbed. When microfluidic devices are not rationally designed, and when the influence of fluidic resistance is not taken into account, sample dispersion can be biased. A bias can influence the output of colorimetric enzymatic assays supported on these microstructures, which are the most common applications of µPADs, demonstrating the need for rational design of microdevices. The third essential component of developing microfluidic devices is their effective testing, especially when incorporating active pumping elements on-chip. To overcome issues in the manual operation or coding for operation of microvalves, a program that can automatically generate sequences for fluidic manipulation in microfluidic processors was written in Python, with the only inputs required from the user being reservoir positions, mixing ratio and the desired input and output reservoirs. To further improve testing and avoid the use of fixed mounts, a modular system was created to aid the testing of devices with different designs, another advance in the area. This research enables better design and testing of microfluidic devices in shorter times and at lower costs, enabling improvements in the interfacing between different unit operations on-chip, a challenge in the microfluidics area. More than that, it also makes this area, traditionally confined into expensive cleanroom facilities, available to more research groups worldwide.Ph.D

Doctor of Philosophy

dissertationMicrofluidics is an emerging field that deals with the technology and science of manipulation of fluid in microchannels. Since its birth in the 1990s, it has now gradually matured into an enabling technology, like microelectronics and software engineering. A majority of current applications of microfluidics are in life sciences. Polydimethylsiloxane (PDMS) is a soft elastomer and a popular material for fabricating microfluidic devices. This is due to PDMS's unique set of material properties and low cost. Furthermore, the unique mechanical properties of thin PDMS layers/membranes (< 200 µm) can be used to increase the functionality of PDMS-based microfluidic systems. In this presentation, three unique neuroscience applications of PDMS-based microfluidic devices are presented. The working principle behind each of these devices depends on the unique properties of thin PDMS layers. In the first project a fabrication protocol was developed to stack 30 patterned 10-um thick PDMS layers on top of each other without any trapped air bubbles or wrinkles. Each PDMS layer was patterned by spin-coating uncured PDMS on a photolithographic micromold at very high spin speeds and thermally curing the layer later. The layer stacking procedure was done manually using no specialized tools and did not cause any layer deformation to inhibit functionality. This fabrication protocol was used to develop the first ever microfluidic Magnetic Resonance Imaging Phantom to stimulate brain white matter. In the second project, laser ablation was used to rapidly prototype micromolds and by using these micromolds a unique fabrication protocol was developed and characterized to build microvalve arrays (consisting of 100s of microvalves) without access to any cleanroom facility. This was achieved by manipulating the stiffness of thin PDMS layers that are inherent part of pneumatic microvalves. These microvalve arrays were used to build a microfluidic platform for manipulation of C. elegans (a type of a small round worm), which are used extensively for neuronal behavioral analysis. In the last project using similar fabrication techniques (as described in the second project) microfluidic genotyping devices are developed for zebrafish embryos that are less than 2 days old. The unique advantage of the microfluidic zebrafish genotyping devices is that they enable researchers to collect genetic material (for genotyping) from a zebrafish embryo (1 to 2 days old) without causing any harm to its health. This capability is not possible with any other model multicellular organism to date. The working principle behind one of the presented genotyping devices depends on the controlled actuation of PDMS membranes

Lab-on-a-chip nucleic-acid analysis towards point-of-care applications

Recent infectious disease outbreaks, such as Ebola in 2013, highlight the need for fast and accurate diagnostic tools to combat the global spread of the disease. Detection and identification of the disease-causing viruses and bacteria at the genetic level is required for accurate diagnosis of the disease. Nucleic acid analysis systems have shown promise in identifying diseases such as HIV, anthrax, and Ebola in the past. Conventional nucleic acid analysis systems are still time consuming, and are not suitable for point-ofcare applications. Miniaturized nucleic acid systems has shown great promise for rapid analysis, but they have not been commercialized due to several factors such as footprint, complexity, portability, and power consumption. This dissertation presents the development of technologies and methods for a labon-a-chip nucleic acid analysis towards point-of-care applications. An oscillatory-flow PCR methodology in a thermal gradient is developed which provides real-time analysis of nucleic-acid samples. Oscillating flow PCR was performed in the microfluidic device under thermal gradient in 40 minutes. Reverse transcription PCR (RT-PCR) was achieved in the system without an additional heating element for incubation to perform reverse transcription step. A novel method is developed for the simultaneous pattering and bonding of all-glass microfluidic devices in a microwave oven. Glass microfluidic devices were fabricated in less than 4 minutes. Towards an integrated system for the detection of amplified products, a thermal sensing method is studied for the optimization of the sensor output. Calorimetric sensing method is characterized to identify design considerations and optimal parameters such as placement of the sensor, steady state response, and flow velocity for improved performance. An understanding of these developed technologies and methods will facilitate the development of lab-on-a-chip systems for point-of-care analysis

HIGH SPEED CONTINUOUS THERMAL CURING MICROFABRICATION SYSTEM

Rapid creation of devices with microscale features is a vital step in the commercialization of a wide variety of technologies, such as microfluidics, fuel cells and self-healing materials. The current standard for creating many of these microstructured devices utilizes the inexpensive, flexible material poly-dimethylsiloxane (PDMS) to replicate microstructured molds. This process is inexpensive and fast for small batches of devices, but lacks scalability and the ability to produce large surface-area materials. The novel fabrication process presented in this paper uses a cylindrical mold with microscale surface patterns to cure liquid PDMS prepolymer into continuous microstructured films. Results show that this process can create continuous sheets of micropatterned devices at a rate of 1.9 in2/sec (~1200 mm2/sec), almost an order of magnitude faster than soft lithography, while still retaining submicron patterning accuracy

Development of a Dual-Modal Microfluidic Paper-Based Analytical Device for the Quantitative and Qualitative Detection of The Total Hardness of Water.

A dip-and-read microfluidic paper-based analytical device (μPAD) was developed for the qualitative and quantitative detection of the total hardness of water. To create well-defined hydrophobic barriers on filter paper, a regular office printer and a commercially available permanent marker pen were utilized as a quick and simple technique with easily accessible equipment/materials to fabricate μPAD in new or resource-limited laboratories without sophisticated equipment. After a wettability and barrier efficiency analysis on the permanent marker colors, the blue and green ink markers exhibited favorable hydrophobic properties and were utilized in the fabrication of the developed test devices. The device had five reaction and detection zones modeled after the classification given by the World Health Organization (WHO), so qualitatively it determined whether the water was ‘soft’, ‘moderately hard’, ‘hard’, or ‘very hard’ by changing color from blue to pink in about 3 min. The device was also used to introduce an alternative colorimetric reaction for quantitative analysis of the water hardness without the need for ethylenediaminetetraacetic acid (EDTA) and without compromising the simplicity and low cost of the device. The developed μPAD showed a calculated limit of detection (LOD) of 0.02 mM, which is at least 80% less than those of commercially available test strips and other reported μPADs, and the results of the real-world samples were consistent with those of the standard titration (with EDTA). In addition, the device exhibited stability for 2 months at room and frigid condition (4 °C) and at varying harsh temperatures from 25 to 100 °C. The results demonstrate that the developed paper-based device can be used for rapid, on-site analysis of water with no interferences and no need for a pipette for sample introduction during testing. A mathematical estimation of the flow of liquid water and blood serum on the fabricated paper device was computed using a geometrically modified version of the Lucas-Washburn equation to predict the signal time of the paper sensor during each test. The estimation correlated excellently with experimental data and observation, hence making the modification of the Lucas-Washburn equation valid specifically for the fabricated μPAD. Finally, all-inclusive pullulan tablets were fabricated as an alternative analytical platform to detect the total hardness of water. The assay was used to compute a calibration curve which can be used to quantify the total hardness of water in about five minutes by just dropping the required number of tablets in the water sample, and a limit of detection of 0.0140 mM was achieved

Doctor of Philosophy

dissertationMicrofluidic methods were applied to nucleic acid mutation identification and quantification. DNA melting analysis interrogation volumes were reduced 4 orders of magnitude (down to 1 nL volumes) from commercial instrumentation, allowing less reagent consumption while yielding adequate signal for genotyping and scanning of polymerase chain reaction (PCR) products. A microfluidic instrument was developed for digital PCR applications, using a spinning plastic disk patterned by xurography. Theplatform offers faster thermocycling times (30 cycles in ~12 min), simplified fluid partitioning, and a less expensive disposable when compared to currently available digital PCR platforms. PCR within the disk was validated by quantifying plasmid DNA sample using "on/off" fluorescence interrogation across 1000 wells (30 nL/well) at varying template concentration. A 94% PCR efficiency and product amplification specificity were determined by aggregate real-time PCR and melting analysis. The technique of quasi-digital PCR was also applied within this platform, wherein a single mutation copy was preferentially amplified from a large background of wild-type DNA, to detect and quantify low levels of rare mutations. This method demonstrated a sensitivity of 0.01% (detecting a mutant to wild-type DNA ratio of 43:450000), by mixing known concentrations of an oncogene mutation with thousands of wild-type template copies. Statistic analysis tools were constructed in order to interpret digital PCR data, with results comparing well to DNA absorption measurements

Passive micromixers and organic electrochemical transistors for biosensor applications

Fluid handling at the microscale has greatly affected different fields such as biomedical, pharmaceutical, biochemical engineering and environmental monitoring due to its reduced reagent consumption, portability, high throughput, lower hardware cost and shorter analysis time compared to large devices. The challenges associated with mixing of fluids in microscale enabled us in designing, simulating, fabricating and characterizing various micromixers on silicon and flexible polyester substrates. The mixing efficiency was evaluated by injecting the fluids through the two inlets and collecting the sample at outlet. The images collected from the microscope were analyzed, and the absorbance of the color product at the outlet was measured to quantify the mixing efficacy. A mixing efficiency of 96% was achieved using a flexible disposable micromixer. The potential for low-cost processing and the device response tuning using chemical doping or synthesis opened doorways to use organic semiconductor devices as transducers in chemical and biological sensor applications. A simple, inexpensive organic electrochemical transistor (OECT) based on conducting polymer poly(3,4- ethyelenedioxythiphene) poly(styrene sulfonate) (PEDOT:PSS) was fabricated using a novel one step fabrication method. The developed transistor was used as a biosensor to detect glucose and glutamate. The developed glucose sensor showed a linear response for the glucose levels ranging from 1 μM-10 mM and showed a decent response for the glucose levels similar to those found in human saliva and to detect glutamate released from brain tumor cells. The developed glutamate sensor was used to detect the glutamate released from astrocytes and glioma cells after stimulation, and the results are compared with fluorescent spectrophotometer. The developed sensors employ simple fabrication, operate at low potentials, utilize lower enzyme concentrations, do not employ enzyme immobilization techniques, require only 5 μL of both enzyme and sample to be tested and show a stable response for a wide pH ranging from 4 to 9

Flexible stretchable electronics for sport and wellbeing applications

Wearable electronics are becoming increasingly widespread in modern society. Though these devices are intended to be worn, integrated into clothing and other everyday objects, the technologies and processes used to manufacture them is no different than those that manufacture laptops and mobile phones. Many of these devices are intended to monitor the user’s health, activity and general wellbeing, within clinical, recreational and assistive environments. Consequently, the inherent incompatibility of these rigid devices with the soft, elastic structure of the human body can in some cases can be uncomfortable and inconvenient for everyday life. For devices to take the step from a ‘wearable’ to an ‘invisible’, a drastic rethinking of electronics manufacturing is required.The fundamental aim of this research is to establish parameters of usefulness and an array of materials with complimentary processes that would assist in transitioning devices to long term almost invisible items that can assist in improving the health of the wearer. In order to approach this problem, a novel architecture was devised that utilised PDMS as a substrate and microfluid channels of Galinstan liquid alloy for interconnects. CO2 laser machining was investigated as a means of creating channels and vias on PDMS substrates. Trace speeds and laser power outputs were investigated in order to find an optimal combination. The results displayed upper limits for power densities; where surpassing this limit resulted in poor repeatability and surface finish. It was found that there was an optimal set of trace speeds that ranged from approximately 120mm/s to 190mm/s that resulted in the most reliable and repeatable performance. Due to the complex nature of a materials variable energy absorption properties, it is not possible to quantify a single optimal parameter set.To understand the performance of these devices in situ, finite element analysis was employed to model deformations that such a device could experience. The aims here were to investigate the bond strength required to prevent delamination, between the silicon-PDMS and PDMS-PDMS bonds, in addition to the stress applied to the silicone die during these deformations. Based upon the applied loads the required bond strengths would need to be at least ~65kPa to maintain PDMS-PDMS adhesion during these tests, while stress on the silicone-PDMS adhesion required an expected v higher ~160kPa, both of which are within the reach of existing bonding techniques that are capable of withstanding a pressure of ~600kPa before failure occurs. Stress on the silicon die did not exceed ~7.8 MPa during simulation, which is well below the fracture stress.By developing knowledge about how various components of such a system will respond during use and under stress, it allows future engineers to make informed design decisions and develop better more resilient products.</div