Microsystems create new opportunities for the spatial and temporal control of cell growth and stimuli by combining surfaces that mimic complex biochemistries and geometries of the extracellular matrix with microfluidic channels that regulate transport of fluids and soluble factors. Further integration with bioanalytic microsystems results in multifunctional platforms for basic biological insights into cells and tissues, as well as for cell-based sensors with biochemical, biomedical and environmental functions. Highly integrated microdevices show great promise for basic biomedical and pharmaceutical research, and robust and portable point-of-care devices could be used in clinical settings, in both the developed and the developing world.

Cells on chips

Fundamental and applied research in chemistry and biology benefits from opportunities provided by droplet-based microfluidic systems. These systems enable the miniaturization of reactions by compartmentalizing reactions in droplets of femoliter to microliter volumes. Compartmentalization in droplets provides rapid mixing of reagents, control of the timing of reactions on timescales from milliseconds to months, control of interfacial properties, and the ability to synthesize and transport solid reagents and products. Droplet-based microfluidics can help to enhance and accelerate chemical and biochemical screening, protein crystallization, enzymatic kinetics, and assays. Moreover, the control provided by droplets in microfluidic devices can lead to new scientific methods and insights.

/pdf/reactions-in-droplets-in-microfluidic-channels-22iig0bcxm.pdf

Reactions in Droplets in Microfluidic Channels

Polymer surface modification for the attachment of bioactive compounds

Introduction A Why POC Diagnostics? B Time B Patient Responsibility and Compliance B Cost B Diagnostic Targets C Proteins C Metabolites and Other Small Molecules C Nucleic Acids C Human Cells D Microbes/Pathogens D Drugs and Food Safety D Current Context of POC Assays E POC Glucose Assays E Lateral Flow Assays E Limitations of “Traditional” POC Approaches F Enabling Technologies G Printing and Laminating G Microfluidic Technologies and Approaches: “Unit Operations” for POC Devices G Pumping and Valving H Mixing I Separation I Reagent Storage J Sample Preparation K Surface Chemistry and Device Substrates L Physical Adsorption L Bioaffinity Attachment L Covalent Attachment M Substrate Materials M Detection M Electrochemical Detection N Optical Detection N Magnetic Detection N Label-Free Methods O Enabling Multiplexed Assays O Recent Innovation O Lateral Flow Assay Technologies O Proteins P Antibodies P Protein Expression and Purification Q Nucleic Acids Q Aptamers R Infectious Diseases and Food/Water Safety R Blood Chemistry S Coagulation Markers S Whole Cells S Trends, Unmet Needs, Perspectives T Glucose T Global Health and the Developing World T Personalized Medicine and Home Testing U Technology Trends U Multiplexing V Author Information V Biographies V Acknowledgment W References W

/pdf/point-of-care-diagnostics-status-and-future-5c7xkio6mh.pdf

Point of care diagnostics: Status and future

Micro total analysis systems. Latest advancements and trends.

The use of direct-write laser micromachining on poly(methyl methacrylate) (PMMA) to fabricate microfluidic chip has the potential for fast prototyping and production. However, the advantage has been diminished by the rugged surface and the limited surface chemistry modification available. To overcome this problem, we have developed a flexible and economic pipeline including PMMA micromachining, surface smoothness improvement, and a universal surface modification for introduction of various functional groups. The micromachining is accomplished by a commercial laser scriber, to which a user designed computer drawing is sent directly for grooving. The typical trench width is 140m while the aspect ratio up to more than 7 is easily achieved. Smooth surface is obtained after a one-step thermal annealing treatment after machining. The chemical modification is performed by a simple reduction reaction followed by the widely used organosilane chemistry to introduce diverse functional groups such as perfluoroalkyl (–C nF2n+2), amino (–NH2), and sulfhydryl (–SH) for surface passivation or further biomolecule immobilization. The surface smoothness after thermal annealing has been examined by scanning electron microscopy (SEM) and atomic force microscopy (AFM) to be comparable to pristine surface. The surface chemistry modification has been confirmed by attenuated total reflectance–Fourier transform infrared spectroscopy (ATR–FTIR) and X-ray photoelectron spectroscopy (XPS). The whole procedure provides a very efficient micromachining platform to fabricate PMMA microfluidic chip for both prototyping and production. © 2003 Elsevier B.V. All rights reserved.

Direct-write laser micromachining and universal surface modification of PMMA for device development

Glass is an excellent material for use as a microfluidic chip substrate because it has great chemical and thermal stability. This work describes a flexible platform for the rapid prototyping of microfluidic chips fabricated from glass. A debris-free laser direct-writing technology that requires no photomask generation is developed. A 266 nm laser with a high repetition rate is employed in laser-induced backside wet etching (LIBWE) for glass machining. A microfluidic pattern is designed using computer drawing software and then automatically translated into computer numerical control motion so that the microtrench is directly fabricated on the glass chip. The overall machining speed can be increased by increasing the repetition rate to ~6 kHz. Without a clean room facility or the highly corrosive acid, HF, the overall development time is within hours. Trenches with complex structures that are hard to fabricate by photolithography were easily produced by laser direct-writing. An integrated microreactor/concentrator is demonstrated. The crack-free and debris-free surface was characterized by SEM and a surface profiler. Various effective etching chemicals for the LIBWE process were investigated to understand the etching mechanism. The minimal laser power used for glass etching was approximately 20 mW for a 6 µm wide microtrench. Several new compounds have been demonstrated to be effective in ablation. The etch threshold is minimum and does not decrease further as the unit length absorbance increases above 8000 in acetone solution.

https://iopscience.iop.org/article/10.1088/0960-1317/15/6/005/pdf

Crack-free direct-writing on glass using a low-power UV laser in the manufacture of a microfluidic chip

This work describes a novel and simple modification of the current microarray format. It reduces the sample/reagent volume to 1 microl and the hybridization time to 500 s. Both 20mer and 80mer oligonucleotide probes and singly labeled 20mer and 80mer targets, representative of the T-cell acute lymphocytic leukemia 1 (TAL1) gene, have been used to elucidate the performance of this hybridization approach. In this format, called shuttle hybridization, a conventional flat glass DNA microarray is integrated with a PMMA microfluidic chip to reduce the sample and reagent consumption to 1/100 of that associated with the conventional format. A serpentine microtrench is designed and fabricated on a PMMA chip using a widely available CO2 laser scriber. The trench spacing is compatible with the inter-spot distance in standard microarrays. The microtrench chip and microarray chip are easily aligned and assembled manually so that the microarray is integrated with a microfluidic channel. Discrete sample plugs are employed in the microchannel for hybridization. Flowing through the microchannel with alternating depths and widths scrambles continuous sample plug into discrete short plugs. These plugs are shuttled back and forth along the channel, sweeping over microarray probes while re-circulation mixing occurs inside the plugs. Integrating the microarrays into the microfluidic channel reduces the DNA-DNA hybridization time from 18 h to 500 s. Additionally, the enhancement of DNA hybridization reaction by the microfluidic device is investigated by determining the coefficient of variation (CV), the growth rate of the hybridization signal and the ability to discriminate single-base mismatch. Detection limit of 19 amol was obtained for shuttle hybridization. A 1 mul target was used to hybridize with an array that can hold 5000 probes.

/pdf/using-a-microfluidic-device-for-1-ml-dna-microarray-viwg7h4t6f.pdf

Using a microfluidic device for 1 μl DNA microarray hybridization in 500 s

This work presents a novel microfluidic coculture system that improves the accuracy of evaluating the interaction between cocultured cell types. A microfluidic coculture chip, fabricated by CO2 laser direct-writing on polymethyl methacrylate (PMMA), was designed to separate two cell types using a microchannel, while permitting transfer of cellular media. The system has two up-stream wells and five down-stream wells. As an example, released inflammatory cytokines (e.g., interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), activated in up-stream macrophages, flow through a microfluidic mixing system, generating linear concentration gradients in down-stream wells and inducing down-stream osteoblasts to release prostaglandin E2 (PGE2), a well-known bone resorption marker. Osteoblast viability was assessed by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. This novel coculture system can be applied to evaluate cell-cell interaction while physically separating interacting cells.

Elucidating in vitro cell-cell interaction using a microfluidic coculture system.

This paper uses a widely available CO2 laser scriber (λ = 10.6 µm) to perform the direct-writing ablation of quartz, borofloat and pyrex substrates for the development of microfluidic chips and cell chips. The surface quality of the ablated microchannels and the presence of debris and distortion are examined by scanning electron microscopy, atomic force microscopy and surface profile measurement techniques. The developed laser ablation system provides a versatile and economic approach for the fabrication of glass microfluidic chips with crack-free structures. In the laser writing process, the desired microfluidic patterns are designed using commercial computer software and are then transferred to the laser scriber to ablate the trenches. This process eliminates the requirement for corrosive chemicals and photomasks, and hence the overall microchip development time is limited to less than 24 h. Additionally, since the laser writing process is not limited by the dimensions of a photomask, the microchannels can be written over a large substrate area. The machining capability and versatility of the laser writing system are demonstrated through its application to the fabrication of a borofloat microfluidic chip and the writing of a series of asymmetric trenches in a microwell array. It is shown that the minimum attainable trench width is 95 µm and that the maximum trench depth is 225 µm. The system provides an economic and powerful means of rapid glass microfluidic chip development. A rapid cell-patterning method based on this method is also demonstrated.

https://iopscience.iop.org/article/10.1088/0960-1317/16/7/006/pdf

Cheng-Wey Wei

Papers

Direct-write laser micromachining and universal surface modification of PMMA for device development

Crack-free direct-writing on glass using a low-power UV laser in the manufacture of a microfluidic chip

Using a microfluidic device for 1 μl DNA microarray hybridization in 500 s

Elucidating in vitro cell-cell interaction using a microfluidic coculture system.

Rapid cell-patterning and microfluidic chip fabrication by crack-free CO2 laser ablation on glass