Single Substrate Electromagnetic Actuator

A microvalve which utilizes a low temperature ( <300° C.) fabrication process on a single substrate. The valve uses buckling and an electromagnetic actuator to provide a relatively large closing force and lower power consumption. A buckling technique of the membrane is used to provide two stable positions for the membrane, and to reduce the power consumption and the overall size of the microvalve. The use of a permanent magnet is an alternative to the buckled membrane, or it can be used in combination with the buckled membrane, or two sets of micro-coils can be used in order to open and close the valve, providing the capability for the valve to operate under normally opened or normally closed conditions. Magnetic analysis using ANSYS 5.7 shows that the addition of Orthonol between the coils increases the electromagnetic force by more than 1.5 times. At a flow rate of 1 mL/m, the pressure drop is < 100 Pa. The maximum pressure tested was 57 kPa and the time to open or close the valve in air is under 100 ms. This results in an estimated power consumption of 0.1 mW.Georgia Tech Research Corp

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

Development of a PDMS Based Micro Total Analysis System for Rapid Biomolecule Detection

The emerging field of micro total analysis system powered by microfluidics is expected to revolutionize miniaturization and automation for point-of-care-testing systems which require quick, efficient and reproducible results. In the present study, a PDMS based micro total analysis system has been developed for rapid, multi-purpose, impedance based detection of biomolecules. The major components of the micro total analysis system include a micropump, micromixer, magnetic separator and interdigitated electrodes for impedance detection. Three designs of pneumatically actuated PDMS based micropumps were fabricated and tested. Based on the performance test results, one of the micropumps was selected for integration. The experimental results of the micropump performance were confirmed by a 2D COMSOL simulation combined with an equivalent circuit analysis of the micropump. Three designs of pneumatically actuated PDMS based active micromixers were fabricated and tested. The micromixer testing involved determination of mixing efficiency based on the streptavidin-biotin conjugation reaction between biotin comjugated fluorescent microbeads and streptavidin conjugated paramagnetic microbeads, followed by fluorescence measurements. Based on the performance test results, one of the micromixers was selected for integration. The selected micropump and micromixer were integrated into a single microfluidic system. The testing of the magnetic separation scheme involved comparison of three permanent magnets and three electromagnets of different sizes and magnetic strengths, for capturing magnetic microbeads at various flow rates. Based on the test results, one of the permanent magnets was selected. The interdigitated electrodes were fabricated on a glass substrate with gold as the electrode material. The selected micropumps, micromixer and interdigitated electrodes were integrated to achieve a fully integrated microfluidic system. The fully integrated microfluidic system was first applied towards biotin conjugated fluorescent microbeads detection based on streptavidin-biotin conjugation reaction which is followed by impedance spectrum measurements. The lower detection limit for biotin conjugated fluorescent microbeads was experimentally determined to be 1.9 x 106 microbeads. The fully integrated microfluidic system was then applied towards immuno microbead based insulin detection. The lower detection limit for insulin was determined to be 10-5M. The total detection time was 20 min. An equivalent circuit analysis was performed to explain the impedance spectrum results

Design of a Micropump

A micropump which can be produced using conventional production techniques and materials is presented. The micropump is capable of pumping both liquid and gas and is self-priming, which means that it can start pumping gas in a dry state and automatically fills with liquid. Basically, the micropump consists of two parts, a flat valve assembly with two passive membrane valves and an actuator placed on top. Two types of actuators have been applied to drive the pump; an electromagnetic actuator consisting of a magnet placed in a coil and secondly a disk. A disadvantage of the electromagnetic actuator was the relatively large volume occupied by the coil giving the micropump final dimensions of 10×10×8 mm3. Application of the piezoelectric actuator reduced these dimensions down to 12×12×2 mm3 with comparable performance

Development of micropump for microfluidic applications

This dissertation covers the research work on two types of micropumps, one is based on magnetohydrodynamic (MHD) principle that utilizes Lorentz force for actuation, and the other is based on electrochemical actuation. The AC-type MHD micropump was designed and analyzed as a solution to the bubble formation problem encountered in DC-type MHD micropump. A UV-LIGA process using thick layer of SU-8 negative photoresist was successfully developed to microfabricate the AC MHD micropump. Preliminary studies and tests of the AC MHD micropumps demonstrate that bubble formation was significantly reduced to permit the proper function of the micropump. A continuous flow was also successfully demonstrated with no moving mechanical parts needed. To develop the mathematical model for flow of conductive fluids between the electrodes was a challenging issue. To overcome this problem, the impedance of conductive fluids between two electrodes was measured by Electrochemical Impedance Spectroscopy, which then helped to obtain a relatively accurate mathematical model for the system. The design, simulation, fabrication, and test results of the AC MHD micropump are presented in this dissertation. Electrochemical actuator was investigated for micropumping applications. In our research efforts to develop DC-type MHD micropump, bubble formation problem caused by electrolysis proved to be one of the most difficult issues. However, microactuation based on expanding bubbles from electrolysis effect has scale advantages compared with other commonly used microactuation mechanisms. It can therefore be used as a very efficient actuation source for micropumping applications. We have designed, analyzed, and fabricated a microactuator based on the electrochemical principle. Preliminary experiments have proved that the bubbles generated in electrolysis can be manipulated by carefully controlling the direction and amplitude of the input signal. This has demonstrated that efficient pumping at micro volume of fluid can be realized by addition of required valves. The microfluidic system with micropump and integrated active microvalve has been successfully demonstrated. The working principle, design, simulation, and preliminary results of the electrochemical actuator have also been presented in the dissertation

Fabrication and Characterization of Magnetic Nanoparticle Composite Membranes

To effectively and accurately deliver drugs within the human body, both new designs and components for implantable micropumps are being studied. Designs must ensure high biocompatibility, drug compatibility, accuracy and small power consumption. The focus of this thesis was to fabricate a prototype magnetic nanoparticle membrane for eventual incorporation into a biomedical pump and then determine the relationship between this membrane deflection and applied pneumatic or magnetic force. The magnetic nanoparticle polymer composite (MNPC) membranes in this study were composed of crosslinked polydimethylsiloxane (PDMS) and iron oxide nanoparticles (IONPs). An optimal iron oxide fabrication route was identified and particle size in each batch was approximately 24.6 nm. Once these nanoparticles were incorporated into a membrane (5 wt. %), the nanoparticle formed agglomerates with an average diameter of 2.26 ±1.23 µm. Comparisons between the 0 and 5 wt. % loading of particles into the membranes indicated that the elastic modulus of the composite decreased with increasing particle concentration. The pressure- central deflection of the membranes could not be predicated by prior models and variation between magnetic and pneumatic pressure-deflection curves was quantified. Attempts to fabricate membranes with above 5 wt. % nanoparticles were not successful (no gelation). Fourier Transform Infrared (FTIR) spectroscopy results suggest that excess oleic acid on the nanoparticles prior to mixing might have prevented crosslinking

Characterization of Electromagnetic Valveless Micropump

This paper presents an electromagnetically-actuated micropump for microfluidic application. The system comprises two modules; an electromagnetic actuator module and a diffuser module. Fabrication of the diffuser module can be achieved using photolithography process with a master template and a PDMS prepolymer as the structural material. The actuator module consists of two power inductors and two NdFeB permanent magnets placed between the diffuser elements. The choice of this actuation principle merits from low operating voltage (1.5 Vdc) and the flow direction can be controlled by changing the orientation of the magnet vibration. Maximum volumetric flow rate of the fabricated device at zero backpressure is 0.9756 µLs-1 and 0.4659 µLs-1 at the hydrostatic backpressure of 10 mmH2O at 9 Hz of switching speed

Characteristic of Thin Sheet Membrane for a Mechanical Driven Micropump System

This paper demonstrates the characteristic of thin sheet membrane for a mechanical driven micropump system by using a spin coater machine. The moving diaphragm material is made from a PDMS prepolymer material. A 100 mm diameter petri dish is used as the mold template for the membrane fabrication. There are three variables that influence the membrane thickness formation during the spin coating process, which are the prepolymer weight, spin coater spinning rate speed and the spinning time. Based on the study, the optimum parameters to fabricate a 300 µm thin sheet membrane by using a 100 mm diameter of petri dish are 2.5 g of prepolymer, 500 rpm of spin coater speed and 180 s of spin time. These parameters yield a thin sheet membrane for the micropump application with 314.82 ± 3.6556 µm thickness

Magnetically actuated micropumps using an Fe-PDMS composite membrane

Proceedings SPIE International Society for Optical Engineering 6172 (2006). Retrieved April 2006 from http://mems.mem.drexel.edu/actuator.pdfIn this paper we describe a novel Fe-PDMS composite that can be used to create magnetically actuated polymeric microstructures. The composite is formed by suspending <10μm iron particles in polydimethylsiloxane (PDMS) at concentrations ranging from 25-75% by weight. Material properties and processing capabilities have been examined, and to demonstrate the usefulness of this material we have designed, fabricated and tested two prototypical micropumps that utilize an Fe-PDMS actuator membrane