Name: fabricating high-viscosity droplets using microfluidic capillary device with phase-inversion co-flow structure
Uploaded: 2018-04-17T14:00:00.000+00:00
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이 작품은 국립 자연 과학 재단의 중국 (No. 51420105006와 51322501)에 의해 지원 되었다. 우리는 높은 점도 아이디어에 도움이 그의 토론을 위한 다니엘을 감사합니다.

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저자는 공개 없다.

위상 반전 공동 흐름 장치 단 분산 높은 점도 물방울을 생성 하는 간단 하 고 똑 바른 앞으로 방법을 제공 합니다. 이 장치 기본 공동 흐름 구조는 출구 출구 배관에 연결 되어 중간 튜브에 삽입 된 튜브의 구성으로 일반적인 공동 흐름 장치에 유사한 구조를가지고 있습니다. 그러나, η > 1 Pa·s의 점도와 높은 점도 방울의 생성에 대 한 위상 반전 공동 흐름 장치 및 일반적인 공동 흐름 장치 사...

방울의 생성 응용 프로그램, 약물 전달, 재료 합성, 3D bioprinting, 세포 분석 실험, 식품 공학1,2,,34 등의 다양 한 핵심 기술 되고있다 , 5 , 6. t-교차점7,8, 미세 장치 공동1,9, 흐름 또는 흐름 초점10,11 구조는 널리 단 분산을 생성 하는 데 사용 됩니다 단일 에멀젼 방울입니다. 선택 더 점성 연속 위상의 방울12의 형성을 촉진 한다 그리고 연속 및 이산 체액의 점도 일반적으로 0.1 Pa 드롭릿 마이크로13아래. 그러나, 많은 응용 프로그램에서 분산된 단계 할 수 있습니다는 점도 몇 백 번 이상 물, 글리세롤14, 등의 나노 입자15,16단백질 또는 고분자17 를 포함 하는 솔루션 , 18 , 19, 단 분산 방울 떨어지는 정권11 미세 장치, 특히 η > 1 Pa·s14 의 점성 유체에에서 안정에서 높은 점도 유체에서 직접 달성 하기 어려운 반면 17,,1819. 또한, 그것은 보고13,18 방울 형성에 대 한 일반적인 미세 방법을 상대적으로 낮은 점도 및 안정적인 떨어지는에서 균일 한 방울을 형성 하기 위하여 적당 한 계면 장력 체액 요구 되었습니다. 정권입니다.
0.1 Pa 보다 약간 큰 점도와 분산된 단계에 대 한 일반적인 t-교차점, 공동 흐름 또는 미세 장치 흐름 초점 작은 물방울 형성을 촉진 하기 위하여 몇 가지 가능한 방법 있다: (1) 감소는 분산의 점도 휘발성 용 매11,20;에 그것을 diluting 하 여 위상 (2) 연속 단계1,11;의 점도 증가 시켜 분산-하-연속 점도 비율 감소 (3) 높은 분산 연속 흐름 속도 비율 14,19를 유지 하면서 매우 낮은 값으로 분산 단계의 흐름 속도 감소. 그러나로 그들은 상당히 극적으로 휘발성 용 매 또는 연속 위상의 소비를 올리는 동안 생산 속도 낮출 것 이다,이 접근 훨씬 높은 점도, 유체에 대 한 실용적 되지 않습니다. 이외, 그것은 그 일부 고 점도 폴리머 솔루션 η > 1 Pa·s 여전히 않았다 하지 헤어 방울으로17,19위에서 언급 한 방법으로 보고 되었습니다.
또한 높은 점도 방울의 생성을 용이 하 게 시스템에 액체의 세 번째 단계를 소개 하는 미세 장치의 몇몇 향상 된 디자인 있다. 혁신을 포함: 거품 방울21, dipsersed 단계 및 지속적인 단계18사이 중간 단계로 서 도입 적당 한 점도와 혼합할 수 없는 chaperoning 액체에 잘라 처리 스레드를 도입 하 고 microreactors 두 낮은 점도 선구자21,,2223에서 높은 점도 방울을 생성 하기 위해 도입. 그러나, 한 더 많은 액체는 과정에 참여는, 시스템은 더 복잡 하 고, 고 장치는 일반적으로 단일 에멀젼 방울의 생성에 대 한 전형적인 장치 보다 훨씬 좁은 흐름 정권에서 작동.
단 분산 η > 1 Pa·s, 표면 제어 위상 반전 방법 높은 점성 액체에서 직접 방울 되었습니다 생성 하24조사. 낮은 점도 방울의 생성은 높은 점도 방울12, 높은 점도 연속 단계에 길쭉한 낮은 점도 방울 먼저 일반적인 공동 흐름 구조를 사용 하 여 생성 되 고 나누어진다 면 보다 훨씬 더 쉽게 공동 흐름 구조의 표면 습윤 다운스트림의 변화. 출시 된 저 점도 액체 반비례 캡슐화 다운스트림 높은 점성 액체 방울으로 위상 반전 완료 되도록 합니다. 위상 반전 메커니즘에 따라 단 분산 고 점도 물방울 생성 될 수 있습니다 일반적인 공동 흐름 장치를 기반으로 공동 흐름 장치 출구 낮은 점성 유체에 의해 젖는 취급 고 다음 더 넓은 관24에 연결 ,25.

<table><tbody><tr><td>VitroTubes Glass Tubing</td><td>VitroCom</td><td>8240</td><td>Square - Miniature Hollow Glass Tubing, I.D.=0.4mm, OD=0.8mm</td></tr><tr><td>VitroTubes Glass Tubing</td><td>VitroCom</td><td>CV2033</td><td>Round - Miniature Hollow Glass Tubing, I.D.=0.2mm, O.D.=0.33mm</td></tr><tr><td>VitroTubes Glass Tubing</td><td>VitroCom</td><td>CV1017</td><td>Round - Miniature Hollow Glass Tubing, I.D.=0.1mm, O.D.=0.17mm</td></tr><tr><td>VitroTubes Glass Tubing</td><td>VitroCom</td><td>Q14606</td><td>Square - Miniature Hollow Glass Tubing, I.D.=1.05mm+0.1/-0, OD=1.5mm</td></tr><tr><td>Standard Glass Capillaries</td><td>WPI</td><td>1B100-6</td><td>Round - Glass Tubing, I.D.=0.58mm, O.D.=1.00mm</td></tr><tr><td>Glycerol</td><td>Sinopharm Chemical Reagent Beijing</td><td>10010618</td><td></td></tr><tr><td>Paraffin Liquid</td><td>Sinopharm Chemical Reagent Beijing</td><td>30139828</td><td></td></tr><tr><td>Poly(vinyl alcohol), PVA-124</td><td>Sinopharm Chemical Reagent Beijing</td><td>30153084</td><td></td></tr><tr><td>Span 80</td><td>Sigma-Aldrich</td><td>85548</td><td></td></tr><tr><td>Starch</td><td>Sigma-Aldrich</td><td>S9765</td><td></td></tr><tr><td>Trichloro(octadecyl)silane</td><td>Sigma-Aldrich</td><td>104817</td><td></td></tr><tr><td>Toluidine Blue O</td><td>Sigma-Aldrich</td><td>T3260</td><td></td></tr><tr><td>Honey</td><td></td><td></td><td>Chaste tree honey, common food product purchased from supermarket</td></tr><tr><td>DEVCON 5 Minute Epoxy</td><td>ITW&amp;nbsp;</td><td></td><td>Epoxy glue</td></tr><tr><td>Blunt Tip Stainless Steel Dispensing Needles (Luer Lock)</td><td>Suzhou Lanbo Needle, China</td><td>LTA820050</td><td>20G x 1/2&quot;&amp;nbsp;</td></tr><tr><td>Tungsten/Carbide Scriber</td><td>Ullman</td><td>1830</td><td>For cutting glass tubing</td></tr><tr><td>Microscope Slides</td><td>Sail Brand</td><td>7101</td><td>76.2 mm x 25.4 mm, Thickness 1 - 1.2 mm</td></tr><tr><td>Polyethylene Tubing</td><td>Scientific Commodities</td><td>BB31695-PE/5</td><td>I.D. = 0.86 mm, O.D. = 1.32 mm</td></tr><tr><td>Syringe Pumps</td><td>Longer Pump, China</td><td>LSP01-1A</td><td>3 pumps needed for the experiments</td></tr></tbody></table>

fabricating high-viscosity droplets using microfluidic capillary device with phase-inversion co-flow structure

단 분산 고 점도와 방울의 생성 항상 물방울 마이크로에 도전 하고있다. 여기, 낮은 점성 액체에 균일 한 높은 점도 물방울을 생성 하는 위상 반전 공동 흐름 장치를 설명 합니다. 미세 모 세관 장치 넓은 튜브에 연결 하는 그것의 출구와 일반적인 공동 흐름 구조를가지고 있습니다. 저 점도 액체의 길쭉한 방울 먼저 공동 흐름 구조에 높은 점성 액체에 의해 캡슐화 됩니다. 위상 반전 다음 다음 역에서 출구의 끝에 저 점도 방울의 접착에 의해 유도 된 길쭉한 낮은 점도 방울 낮은 점성 유체에 의해 젖는 취급은, 출구를 통해 흐름 높은 점도 유체 캡슐화 높은 점성 액체에 낮은 점성 액체의 흐름 속도 비율을 변경 하 여 결과 높은 점도 방울의 크기를 조정할 수 있습니다. 높은 점도 11.9 우선권, 글리세롤, 꿀, 녹말, 및 폴리머 솔루션 등까지 점도와 방울의 생성의 몇 가지 전형적인 예를 보여 줍니다. 단 분산 높은 점도 방울 방울-기반 응용 프로그램을, 재료 합성, 약물 전달, 세포 분석 실험, 생명 공학, 그리고 음식 등의 다양 한에서 사용할 수 있는 생성 하는 간단 하 고 간단 접근 방식을 제공 합니다. 공학.

그림 1A와 같이 위상 반전, 공동 흐름 구조와 미세 모 세관 장치 단 분산 수성 높은 점도 작은 물방울을 생성 하도록 설계 되었습니다. 그림 1에서 높은 점도 수성 단계는 ηw 의 점도 글리세롤 = 1.4 파; 저 점도 오일 단계는 ηo 의 점성 있는 액체 파라핀 = 0.029 파; 두 단계 사이 표면 장력은 γ = 27.7 mN/m. ...

Watch this Scientific Journal Video about Fabricating High-viscosity Droplets using Microfluidic Capillary Device with Phase-inversion Co-flow Structure at JoVE.com

Fabricating High-viscosity Droplets using Microfluidic Capillary Device with Phase-inversion Co-flow Structure

위상 반전 공동 흐름 구조와 미세 모 세관 장치를 사용 하 여 조작 높은 점도 방울

위상 반전 공동 흐름 장치는 단 분산 높은 점도 방울 방울 마이크로에서 실현 하기 어려운 1 파 위 생성을 보여 줍니다.

The generation of monodisperse droplets with high viscosity has always been a challenge in droplet microfluidics. Here, we demonstrate a phase-inversion ...

fabricating-high-viscosity-droplets-using-microfluidic-capillary

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10.3K 조회수.  University of Science and Technology Beijing. 위상 반전 공동 흐름 장치는 단 분산 높은 점도 방울 방울 마이크로에서 실현 하기 어려운 1 파 위 생성을 보여 줍니다.

비디오: Fabricating High-viscosity Droplets using Microfluidic Capillary Device with Phase-inversion Co-flow Structure

Fluorescence detection methods for microfluidic droplet platforms

The development of microfluidic platforms for performing chemistry and biology has in large part been driven by a range of potential benefits that accompany system miniaturisation. Advantages include the ability to efficiently process nano- to femoto- liter volumes of sample, facile integration of functional components, an intrinsic predisposition towards large-scale multiplexing, enhanced analytical throughput, improved control and reduced instrumental footprints.1
In recent years much interest has focussed on the development of droplet-based (or segmented flow) microfluidic systems and their potential as platforms in high-throughput experimentation.2-4 Here water-in-oil emulsions are made to spontaneously form in microfluidic channels as a result of capillary instabilities between the two immiscible phases. Importantly, microdroplets of precisely defined volumes and compositions can be generated at frequencies of several kHz. Furthermore, by encapsulating reagents of interest within isolated compartments separated by a continuous immiscible phase, both sample cross-talk and dispersion (diffusion- and Taylor-based) can be eliminated, which leads to minimal cross-contamination and the ability to time analytical processes with great accuracy. Additionally, since there is no contact between the contents of the droplets and the channel walls (which are wetted by the continuous phase) absorption and loss of reagents on the channel walls is prevented.
Once droplets of this kind have been generated and processed, it is necessary to extract the required analytical information. In this respect the detection method of choice should be rapid, provide high-sensitivity and low limits of detection, be applicable to a range of molecular species, be non-destructive and be able to be integrated with microfluidic devices in a facile manner. To address this need we have developed a suite of experimental tools and protocols that enable the extraction of large amounts of photophysical information from small-volume environments, and are applicable to the analysis of a wide range of physical, chemical and biological parameters. Herein two examples of these methods are presented and applied to the detection of single cells and the mapping of mixing processes inside picoliter-volume droplets. We report the entire experimental process including microfluidic chip fabrication, the optical setup and the process of droplet generation and detection.

Droplet-based microfluidic platforms are promising candidates for high throughput experimentation since they are able to generate picoliter, self-compartmentalized vessels inexpensively at kHz rates. Through integration with fast, sensitive and high resolution fluorescence spectroscopic methods, the large amounts of information generated within these systems can be efficiently extracted, harnessed and utilized.

microfluidic 비말 플랫폼 형광 검출 방법

The development of microfluidic platforms for performing chemistry and biology has in large part been driven by a range of potential benefits that ...

연구

생체공학

High Throughput Single-cell and Multiple-cell Micro-encapsulation

Microfluidic encapsulation methods have been previously utilized to capture cells in picoliter-scale aqueous, monodisperse drops, providing confinement from a bulk fluid environment with applications in high throughput screening, cytometry, and mass spectrometry. We describe a method to not only encapsulate single cells, but to repeatedly capture a set number of cells (here we demonstrate one- and two-cell encapsulation) to study both isolation and the interactions between cells in groups of controlled sizes. By combining drop generation techniques with cell and particle ordering, we demonstrate controlled encapsulation of cell-sized particles for efficient, continuous encapsulation. Using an aqueous particle suspension and immiscible fluorocarbon oil, we generate aqueous drops in oil with a flow focusing nozzle. The aqueous flow rate is sufficiently high to create ordering of particles which reach the nozzle at integer multiple frequencies of the drop generation frequency, encapsulating a controlled number of cells in each drop. For representative results, 9.9 &mu;m polystyrene particles are used as cell surrogates. This study shows a single-particle encapsulation efficiency Pk=1 of 83.7% and a double-particle encapsulation efficiency Pk=2 of 79.5% as compared to their respective Poisson efficiencies of 39.3% and 33.3%, respectively. The effect of consistent cell and particle concentration is demonstrated to be of major importance for efficient encapsulation, and dripping to jetting transitions are also addressed. 
Introduction 
Continuous media aqueous cell suspensions share a common fluid environment which allows cells to interact in parallel and also homogenizes the effects of specific cells in measurements from the media. High-throughput encapsulation of cells into picoliter-scale drops confines the samples to protect drops from cross-contamination, enable a measure of cellular diversity within samples, prevent dilution of reagents and expressed biomarkers, and amplify signals from bioreactor products. Drops also provide the ability to re-merge drops into larger aqueous samples or with other drops for intercellular signaling studies.1,2 The reduction in dilution implies stronger detection signals for higher accuracy measurements as well as the ability to reduce potentially costly sample and reagent volumes.3 Encapsulation of cells in drops has been utilized to improve detection of protein expression,4 antibodies,5,6 enzymes,7 and metabolic activity8 for high throughput screening, and could be used to improve high throughput cytometry.9 Additional studies present applications in bio-electrospraying of cell containing drops for mass spectrometry10 and targeted surface cell coatings.11 Some applications, however, have been limited by the lack of ability to control the number of cells encapsulated in drops. Here we present a method of ordered encapsulation12 which increases the demonstrated encapsulation efficiencies for one and two cells and may be extrapolated for encapsulation of a larger number of cells.
To achieve monodisperse drop generation, microfluidic "flow focusing" enables the creation of controllable-size drops of one fluid (an aqueous cell mixture) within another (a continuous oil phase) by using a nozzle at which the streams converge.13 For a given nozzle geometry, the drop generation frequency f and drop size can be altered by adjusting oil and aqueous flow rates Qoil and Qaq. As the flow rates increase, the flows may transition from drop generation to unstable jetting of aqueous fluid from the nozzle.14 
When the aqueous solution contains suspended particles, particles become encapsulated and isolated from one another at the nozzle. For drop generation using a randomly distributed aqueous cell suspension, the average fraction of drops Dk containing k cells is dictated by Poisson statistics, where Dk = &lambda;k exp(-&lambda;)/(k!) and &lambda; is the average number of cells per drop. The fraction of cells which end up in the "correctly" encapsulated drops is calculated using Pk = (k x Dk)/&Sigma;(k' x Dk'). The subtle difference between the two metrics is that Dk relates to the utilization of aqueous fluid and the amount of drop sorting that must be completed following encapsulation, and Pk relates to the utilization of the cell sample. As an example, one could use a dilute cell suspension (low &lambda;) to encapsulate drops where most drops containing cells would contain just one cell. While the efficiency metric Pk would be high, the majority of drops would be empty (low Dk), thus requiring a sorting mechanism to remove empty drops, also reducing throughput.15
Combining drop generation with inertial ordering provides the ability to encapsulate drops with more predictable numbers of cells per drop and higher throughputs than random encapsulation. Inertial focusing was first discovered by Segre and Silberberg16 and refers to the tendency of finite-sized particles to migrate to lateral equilibrium positions in channel flow. Inertial ordering refers to the tendency of the particles and cells to passively organize into equally spaced, staggered, constant velocity trains. Both focusing and ordering require sufficiently high flow rates (high Reynolds number) and particle sizes (high Particle Reynolds number).17,18 Here, the Reynolds number Re =uDh/&nu; and particle Reynolds number Rep =Re(a/Dh)2, where u is a characteristic flow velocity, Dh [=2wh/(w+h)] is the hydraulic diameter, &nu; is the kinematic viscosity, a is the particle diameter, w is the channel width, and h is the channel height. Empirically, the length required to achieve fully ordered trains decreases as Re and Rep increase. Note that the high Re and Rep requirements (for this study on the order of 5 and 0.5, respectively) may conflict with the need to keep aqueous flow rates low to avoid jetting at the drop generation nozzle. Additionally, high flow rates lead to higher shear stresses on cells, which are not addressed in this protocol. The previous ordered encapsulation study demonstrated that over 90% of singly encapsulated HL60 cells under similar flow conditions to those in this study maintained cell membrane integrity.12 However, the effect of the magnitude and time scales of shear stresses will need to be carefully considered when extrapolating to different cell types and flow parameters. The overlapping of the cell ordering, drop generation, and cell viability aqueous flow rate constraints provides an ideal operational regime for controlled encapsulation of single and multiple cells.
Because very few studies address inter-particle train spacing,19,20 determining the spacing is most easily done empirically and will depend on channel geometry, flow rate, particle size, and particle concentration. Nonetheless, the equal lateral spacing between trains implies that cells arrive at predictable, consistent time intervals. When drop generation occurs at the same rate at which ordered cells arrive at the nozzle, the cells become encapsulated within the drop in a controlled manner. This technique has been utilized to encapsulate single cells with throughputs on the order of 15 kHz,12 a significant improvement over previous studies reporting encapsulation rates on the order of 60-160 Hz.4,15 In the controlled encapsulation work, over 80% of drops contained one and only one cell, a significant efficiency improvement over Poisson (random) statistics, which predicts less than 40% efficiency on average.12
In previous controlled encapsulation work,12 the average number of particles per drop &lambda; was tuned to provide single-cell encapsulation. We hypothesize that through tuning of flow rates, we can efficiently encapsulate any number of cells per drop when &lambda; is equal or close to the number of desired cells per drop. While single-cell encapsulation is valuable in determining individual cell responses from stimuli, multiple-cell encapsulation provides information relating to the interaction of controlled numbers and types of cells. Here we present a protocol, representative results using polystyrene microspheres, and discussion for controlled encapsulation of multiple cells using a passive inertial ordering channel and drop generation nozzle.

Combining monodisperse drop generation with inertial ordering of cells and particles, we describe a method to encapsulate a desired number of cells or particles in a single drop at kHz rates. We demonstrate efficiencies twice exceeding those of unordered encapsulation for single- and double-particle drops.

높은 처리량 마이크로 캡슐 단일 셀 및 다중 셀

Microfluidic encapsulation methods have been previously utilized to capture cells in picoliter-scale aqueous, monodisperse drops, providing confinement ...

Capillary-based Centrifugal Microfluidic Device for Size-controllable Formation of Monodisperse Microdroplets

Here, we demonstrate a simple method for the rapid production of size-controllable, monodisperse, W/O microdroplets using a capillary-based centrifugal microfluidic device. W/O microdroplets have recently been used in powerful methods that enable miniaturized chemical experiments. Therefore, developing a versatile method to yield monodisperse W/O microdroplets is needed. We have developed a method for generating monodisperse W/O microdroplets based on a capillary-based centrifugal axisymmetric co-flowing microfluidic device. We succeeded in controlling the size of microdroplets by adjusting the capillary orifice. Our method requires equipment that is easier-to-use than with other microfluidic techniques, requires only a small volume (0.1-1 &#181;l) of sample solution for encapsulation, and enables the production of hundreds of thousands number of W/O microdroplets per second. We expect this method will assist biological studies that require precious biological samples by conserving the volume of the samples for rapid quantitative analysis biochemical and biological studies.

Here, we demonstrate a simple production method for size-controllable, monodisperse, water-in-oil (W/O) microdroplets using a capillary-based centrifugal microfluidic device. This method requires only a small sample volume and enables high-yield production. We expect this method will be useful for rapid biochemical and cellular analyses.

단 분산 미세 방울의 크기가 제어 형성을위한 모세관 기반 원심 미세 유체 장치

Here, we demonstrate a simple method for the rapid production of size-controllable, monodisperse, W/O microdroplets using a capillary-based centrifugal ...

공학

Generation of Size-controlled Poly (ethylene Glycol) Diacrylate Droplets via Semi-3-Dimensional Flow Focusing Microfluidic Devices

Uniform and size-controllable poly (ethylene glycol) diacrylate (PEGDA) droplets could be produced via the flow focusing process in a microfluidic device. This paper proposes a semi-three-dimensional (semi-3D) flow-focusing microfluidic chip for droplet formation. The polydimethylsiloxane (PDMS) chip was fabricated using the multi-layer soft lithography method. Hexadecane containing surfactant was used as the continuous phase, and PEGDA with the ultraviolet (UV) photo-initiator was the dispersed phase. Surfactants allowed the local surface tension to drop and formed a more cusped tip which promoted breaking into tiny micro-droplets. As the pressure of dispersed phase was constant, the size of droplets became smaller with increasing continuous phase pressure before dispersed phase flow was broken off. As a result, droplets with size variation from 1 &#181;m to 80 &#181;m in diameter could be selectively achieved by changing the pressure ratio in two inlet channels, and the average coefficient of variation was estimated to be below 7%. Furthermore, droplets could turn into micro-beads by UV exposure for photo-polymerization. Conjugating biomolecules on such micro-beads surface have many potential applications in the fields of biology and chemistry.

Generation of Size-controlled Poly ethylene Glycol Diacrylate Droplets via Semi-3-Dimensional Flow Focusing Microfluidic Devices

Here, we present a protocol to illustrate the fabrication processes and verifying experiments of a semi-three-dimensional (semi-3D) flow-focusing microfluidic chip for droplet formation.

크기 제어 폴 리 (에틸렌 글리콜) 빛 방울 장치를 통해 세미 3 차원 흐름 초점 미세의 세대

Uniform and size-controllable poly (ethylene glycol) diacrylate (PEGDA) droplets could be produced via the flow focusing process in a microfluidic device. ...

High Speed Droplet-based Delivery System for Passive Pumping in Microfluidic Devices

A novel microfluidic system has been developed that uses the phenomenon of passive pumping along with a user controlled droplet based fluid delivery system. Passive pumping is the phenomenon by which surface tension induced pressure differences drive fluid movement in closed channels. The automated fluid delivery system consists of a set of voltage controlled valves with micro-nozzles connected to a fluid reservoir and a control system. These voltage controlled valves offer a volumetrically precise way to deliver fluid droplets to the inlet of a microfluidic device in a high frequency manner. Based on the  dimensions demonstrated in the current study example, the system is capable of flowing 4 milliliters per minute (through a 2.2mm by 260um cross-sectional channel). Based on these same channel dimensions, fluid exchange of a point inside the channel can be achieved in as little as eight milliseconds. It is observed that there is interplay between momentum of the system (imparted by a combination of the droplets created by the valves and the fluid velocity in the channel), and the surface tension of the liquid. Where momentum provides velocity to the fluid flow (or vice-versa), equilibration of surface tension at the inlet provides a sudden stop to any flow. This sudden stop allows the user to control the flow characteristics of the channel and opens the door for a variety of biological applications, ranging anywhere from reagent delivery to drug-cell studies. It is also observed that when nozzles are aimed at the inlet at shallow angles, the droplet momentum can cause additional interesting fluid phenomena, such as mixing of multiple droplets in the inlet.

A novel microfluidic system has been developed using the phenomenon of passive pumping and a user controlled fluid delivery system. This microfluidic system has the potential to be used in a wide variety of biological applications given its low cost, ease of use, volumetric precision, high speed, repeatability and automation.

Microfluidic 장치에 수동 펌핑을위한 고속 비말 기반 전달 시스템

A novel microfluidic system has been developed that uses the phenomenon of passive pumping along with a user controlled droplet based fluid delivery ...

생물학

Double Emulsion Generation Using a Polydimethylsiloxane (PDMS) Co-axial Flow Focus Device

Double emulsions are useful in a number of biological and industrial applications in which it is important to have an aqueous carrier fluid. This paper presents a polydimethylsiloxane (PDMS) microfluidic device capable of generating water/oil/water double emulsions using a coaxial flow focusing geometry that can be fabricated entirely using soft lithography. Similar to emulsion devices using glass capillaries, double emulsions can be formed in channels with uniform wettability and with dimensions much smaller than the channel sizes. Three dimensional flow focusing geometry is achieved by casting a pair of PDMS slabs using two layer soft lithography, then mating the slabs together in a clamshell configuration. Complementary locking features molded into the PDMS slabs enable the accurate registration of features on each of the slab surfaces. Device testing demonstrates formation of double emulsions from 14 &#181;m to 50 &#181;m in diameter while using large channels that are robust against fouling and clogging.

Double Emulsion Generation Using a Polydimethylsiloxane PDMS Co-axial Flow Focus Device

Microfluidic double emulsions generation typically involves devices with patterned wettability or custom-fabricated glass components. Here we describe the fabrication and testing of an all polydimethylsiloxane (PDMS) double emulsion generator that does not require surface treatment or complicated fabrication processes, and is capable of producing double emulsions down to 14 &#181;m.

폴리 디메틸 실록산 (PDMS) 공동 축류 초점 장치를 사용하여 이중 에멀젼 생성

Double emulsions are useful in a number of biological and industrial applications in which it is important to have an aqueous carrier fluid. This paper ...

Fabricating Degradable Thermoresponsive Hydrogels on Multiple Length Scales via Reactive Extrusion, Microfluidics, Self-assembly, and Electrospinning

While various smart materials have been explored for a variety of biomedical applications (e.g., drug delivery, tissue engineering, bioimaging, etc.), their ultimate clinical use has been hampered by the lack of biologically-relevant degradation observed for most smart materials. This is particularly true for temperature-responsive hydrogels, which are almost uniformly based on polymers that are functionally non-degradable (e.g., poly(N-isopropylacrylamide) (PNIPAM) or poly(oligoethylene glycol methacrylate) (POEGMA)). As such, to effectively translate the potential of thermoresponsive hydrogels to the challenges of remote-controlled or metabolism-regulated drug delivery, cell scaffolds with tunable cell-material interactions, theranostic materials with the potential for both imaging and drug delivery, and other such applications, a method is required to render the hydrogels (if not fully degradable) at least capable of renal clearance following the required lifetime of the material. To that end, this protocol describes the preparation of hydrolytically-degradable hydrazone-crosslinked hydrogels on multiple length scales based on the reaction between hydrazide and aldehyde-functionalized PNIPAM or POEGMA oligomers with molecular weights below the renal filtration limit. Specifically, methods to fabricate degradable thermoresponsive bulk hydrogels (using a double barrel syringe technique), hydrogel particles (on both the microscale through the use of a microfluidics platform facilitating simultaneous mixing and emulsification of the precursor polymers and the nanoscale through the use of a thermally-driven self-assembly and cross-linking method), and hydrogel nanofibers (using a reactive electrospinning strategy) are described. In each case, hydrogels with temperature-responsive properties similar to those achieved via conventional free radical cross-linking processes can be achieved, but the hydrazone cross-linked network can be degraded over time to re-form the oligomeric precursor polymers and enable clearance. As such, we anticipate these methods (which may be generically applied to any synthetic water-soluble polymer, not just smart materials) will enable easier translation of synthetic smart materials to clinical applications.

Protocols are described for the fabrication of degradable thermoresponsive hydrogels based on hydrazone cross-linking of polymeric oligomers on the bulk scale, microscale, and nanoscale, the latter for preparation of both gel nanoparticles and nanofibers.

자기 조립, 분해 Thermoresponsive Hydrogels 반응 압출, 마이크로, 통해 여러 길이 가늠 자에를 조작 하 고 전기

While various smart materials have been explored for a variety of biomedical applications (e.g., drug delivery, tissue engineering, bioimaging, etc.), ...

Glass-Based Devices to Generate Drops and Emulsions

In this manuscript, three different step-by-step protocols to generate highly monodisperse emulsion drops using glass-based microfluidics are described. The first device is built for the generation of simple drops driven by gravity. The second device is designed to generate emulsion drops in a coflowing scheme. The third device is an extension of the coflowing device with the addition of a third liquid that acts as an electric ground, allowing the formation of electrified drops that subsequently discharge. In this setup, two of the three liquids have an appreciable electrical conductivity. The third liquid mediates between these two and is a dielectric. A&#160;voltage difference applied between the two conducting liquids creates an electric field that couples with hydrodynamic stresses of the coflowing liquids, affecting the jet and drop formation process. The addition of the electric field provides a path to generate smaller drops than in simple coflow devices and for generating particles and fibers with a wide range of sizes.

Here, a protocol to manufacture glass-based microfluidic devices used for generating highly monodisperse emulsions with controlled drop size is presented.

방울과 에멀젼을 생성하는 유리 기반 장치

In this manuscript, three different step-by-step protocols to generate highly monodisperse emulsion drops using glass-based microfluidics are described. ...

Multi-step Variable Height Photolithography for Valved Multilayer Microfluidic Devices

Microfluidic systems have enabled powerful new approaches to high-throughput biochemical and biological analysis. However, there remains a barrier to entry for non-specialists who would benefit greatly from the ability to develop their own microfluidic devices to address research questions. Particularly lacking has been the open dissemination of protocols related to photolithography, a key step in the development of a replica mold for the manufacture of polydimethylsiloxane (PDMS) devices. While the fabrication of single height silicon masters has been explored extensively in literature, fabrication steps for more complicated photolithography features necessary for many interesting device functionalities (such as feature rounding to make valve structures, multi-height single-mold patterning, or high aspect ratio definition) are often not explicitly outlined. 
Here, we provide a complete protocol for making multilayer microfluidic devices with valves and complex multi-height geometries, tunable for any application. These fabrication procedures are presented in the context of a microfluidic hydrogel bead synthesizer and demonstrate the production of droplets containing polyethylene glycol (PEG diacrylate) and a photoinitiator that can be polymerized into solid beads. This protocol and accompanying discussion provide a foundation of design principles and fabrication methods that enables development of a wide variety of microfluidic devices. The details included here should allow non-specialists to design and fabricate novel devices, thereby bringing a host of recently developed technologies to their most exciting applications in biological laboratories.

Multilayer microfluidic devices often involve the fabrication of master molds with complex geometries for functionality. This article presents a complete protocol for multi-step photolithography with valves and variable height features tunable to any application. As a demonstration, we fabricate a microfluidic droplet generator capable of producing hydrogel beads.

판막 다층 미세 유체 장치에 대한 여러 단계의 변수 높이 포토 리소그래피

Microfluidic systems have enabled powerful new approaches to high-throughput biochemical and biological analysis. However, there remains a barrier to ...

조합 플러그 생산을 위한 미세유체 장치 설정

Bilayer Microfluidic Device for Combinatorial Plug Production

Droplet microfluidics is a versatile tool that allows the execution of a large number of reactions in chemically distinct nanoliter compartments. Such systems have been used to encapsulate a variety of biochemical reactions - from incubation of single cells to implementation of PCR reactions, from genomics to chemical synthesis. Coupling the microfluidic channels with regulatory valves allows control over their opening and closing, thereby enabling the rapid production of large-scale combinatorial libraries consisting of a population of droplets with unique compositions. In this paper, protocols for the fabrication and operation of a pressure-driven, PDMS-based bilayer microfluidic device that can be utilized to generate combinatorial libraries of water-in-oil emulsions called plugs are presented. By incorporating software programs and microfluidic hardware, the flow of desired fluids in the device can be controlled and manipulated to generate combinatorial plug libraries and to control the composition and quantity of constituent plug populations. These protocols will expedite the process of generating combinatorial screens, particularly to study drug response in cells from cancer patient biopsies.

저자 스포트라이트: Integrating Computational and Experimental Approaches in Precision Oncology

The fabrication of a polydimethylsiloxane (PDMS)-based bilayer device for the production of combinatorial libraries in water-in-oil emulsions (plugs) is presented here. The necessary hardware and software required to automate plug production are detailed in the protocol, and the production of a quantitative library of fluorescent plugs is also demonstrated.

조합 플러그 생산을 위한 이중층 미세유체 장치

Droplet microfluidics is a versatile tool that allows the execution of a large number of reactions in chemically distinct nanoliter compartments. Such ...