The definition of what could be considered an artificial cell is quite broad due to the immense range of complexity that these micromachines can possess. When talking about artificial cells, names like synthetic cells, minimal cells or protocells are sometimes used interchangeably. One commonly used definition of ACs is that they are structures that are equipped with cellular machinery and can perform biomimetic functions such as in vitro transcription-translation, DNA amplification, energy generation or motility.

ACs can take the forms of bioactive molecules/complexes that are compartmentalized by membranes composed of natural^1,2 or synthetic³ surfactants, particles or polymers. ACs can also take form as membrane-less structures formed due to the physical properties of their components⁴. Synthetic building blocks have been used to create novel biomimetic structures capable of mimicking communication via signaling⁵, phagocytosis⁶ and “predator-prey” behavior³. Liposomes composed of phospholipids are the most commonly used chassis for ACs due to their close resemblance to biological membranes, and for this reason, they are the focus of this article.

State-of-the-art advances in liposome-based AC functionalization have enabled ACs to mimic cellular processes such as communication⁷, growth⁸, division⁹, ability to change morphology¹⁰, the equipment of purified⁴ and synthetic organelles¹¹. Artificial cells have been engineered to utilize biological cells as organelles in biohybrid systems¹² and to generate controlled multivesicular compartments that can mimic signalling pathways¹³. ACs possessing crucial cellular components such as a cytoskeleton¹⁴, ATP¹⁵ or phospholipid¹⁶ synthesis apparatus have also been developed. Further customization of ACs could potentially lead to the development of robust life-like cells for applications in drug delivery/therapeutics¹⁷, biosensor development¹⁸ and generation of artificial tissues¹⁹. Illustrations summarizing the described achievements using liposomes as AC precursors are shown in figure 1.

Figure 1. Scheme displaying the biomimetic abilities of artificial cells (illustration made using Biorender).

Even though significant progress has been made in AC generation there are still prevailing issues that involve, but are not limited to, the uniformity and viability of AC populations. Uniformity of AC populations will be taken into consideration first. Bulk liposome production methods such as electroformation, inverted emulsion transfer and extrusion have enabled researchers to produce high yields of polydisperse liposomes that are very useful for testing different AC design concepts. In order to develop and optimize ACs to fit the standards (such as stability, robust functionality, size) required for their applications, the AC populations should be homogeneous in their bulk properties. This is necessary for predicting and quantifying the behaviour of AC populations, e.g. what fraction of ACs express the desired protein or respond to stimuli from the environment. AC monodispersity could also be an important parameter in monitoring proliferation and the effects of AC volume on their engineered processes’ e.g. protein signalling in designed complex pathways.

Generating ACs using microfluidic techniques can provide high levels of production control. Microfluidic devices used for AC generation include chips made form glass²⁰ and PDMS²¹. One of the techniques for producing highly monodisperse liposomes as precursors for ACs involves liposome generation using double emulsion droplets with octanol and phospholipids as the middle phase. Due to the nature of chemicals used in this method, excess solvent droplets pinch off the double emulsion droplets and are separated, leaving a liposome-pure population ^21,22 (shown in figure 2.A). Another microfluidics-based method involves a gravity-driven transfer of water-in-oil phospholipid monolayer-stabilized droplets from an oil phase to an aqueous phase through another lipid monolayer separating the two phases¹². Crossing this phospholipid separated interphase, the phospholipid monolayer-stabilized droplet develops a bilayer (shown in figure 2.B). There have also been efforts to develop a microfluidics-based method of producing droplet networks, where all droplets have a lipid bilayer at their contact area²³. These cell-like droplet arrays can exchange compounds by diffusion through the lipid bilayer and act like microreactors (shown in figure 2.C).

Figure 2. Microfluidic techniques used to generate liposomes: A) octanol-assisted liposome assembly; B) liposome assembly using the phase transfer method; C) droplet network production using microfluidics. Illustration made using Biorender.

Another fundamental aspect of generating robust ACs is the manipulation of their viability. This is an important factor for their applicability as the ACs lifetime can direct what kind of application they can be used for. Taking ACs able to communicate with the local bacteria population that inhabit a polluted water source as an example, the amount of time an AC can survive in such conditions is dependent on its designed function. Will the AC monitor the pollution levels long-term or would the AC send a signal to the local microorganism population to perform a specific task and after the task is complete it can biodegrade? Environmental factors can also affect the applicability of ACs. Consider a therapeutic AC, that can transfer drug molecules to a medical target. The drug-loaded AC would circulate in the patient’s blood undetected by the immune system, reach the target and respond to stimuli (e.g. biomarker, pH) by slowly releasing the drug cargo. In this example, the therapeutic AC must sustain stability when different environmental factors such as pH changes or macrophages are present.

Conditions that can affect the AC viability require optimization and close monitoring. Microfluidic chips can be used to trap²⁴ and monitor ACs²⁵. The viability of AC populations could be tested under controlled conditions, where nutrients are being pumped into the trapped AC population and different chemical compositions of surrounding media and its changes could be evaluated. These microfluidic chips would function as micro-incubators and could be used to predict how ACs would behave in natural environments. Further customization of described micro-incubators would evolve into lab-on-chip devices that could be used to mechanically manipulate the AC shape²⁶, size²⁷ and sort them by size²⁸. The foundation for these microreactors has been designed by numerous research groups. Joint collaborations from researchers of different disciplines are needed to make these ideas a reality.

The ACs research field is garnering more and more attention and research groups form large collaborations, such as the Bristol and Max Planck institute project MaxSynBio, the USA collaborative project Build-a-Cell or the London-based Imperial College London and Kings College London joint research project fabriCELL. Synthetic biology is not regarded as science fiction but is considered a great investment opportunity. Just this year synthetic biology commercialization was vastly discussed in the synthetic biology conference SynbiTECH2019 in London where key stakeholders from different industrial and academic backgrounds gathered to discuss how to create a multibillion-dollar synthetic industry. Robust ACs are going to be the next innovation that will be crucial not only for fundamental studies, but also for numerous applications that require programmed structures that can perform complex tasks such as interactions with pathogens, pollutants, cancer cells, damaged cells or to act as microreactors, biosensors, constituents of artificial tissues/organs. The utilization of microfluidic techniques is essential for accelerating the AC field growth and as a tool for quality control of ACs as a product.

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Greta Zubaite

I am a Leverhulme Trust funded PhD student at Imperial College London working on artificial/biohybrid cell generation and application. I finished my Biochemistry Bachelor's and Master's degrees at Vilnius University, Lithuania. During this time, I used droplet microfluidics to work on cell-free protein expression using DNA microparticles. I had an internship at the Max Planck Institute for Biochemistry, where I studied Huntington disease yeast model morphology using CryO EM. I also had the chance to do an internship at the University of Cambridge, where I explored double emulsion and liposome generation using droplet microfluidics. In my free time, I enjoy painting and drawing.

Elani Soft Microsystems Group

The Membrane Biophysics Group

• g.zubaite18@imperial.ac.uk
• https://www.imperial.ac.uk/people/g.zubaite18

The post How Could Microfluidic Techniques Be Used to Improve Artificial Cell Development? appeared first on The MicroFluidic Circle.

Figure 1. Example of a pneumatic gripper, grabbing an egg⁵,⁶.

In recent years, the advances in micro and nanotechnology and stimuli-responsive materials allowed the development of micro and nanoscale soft-robots. Why is so important to have a soft and relatively small robot? If we think about a tool to maneuver biological samples, being it for medical applications or simply for biological research, its mechanical properties (stiffness and elasticity, i.e., being soft or stiff and elastic or brittle) and overall dimensions should be comparable to properties of their targets. These miniaturized soft robots could potentially be used for medical operations, therapeutic or diagnostic, and drug delivery in a non-invasively way if they fulfill some important and challenging requirements.

To be able to access and navigate in certain areas of the human body these robots should be soft and small enough to avoid damaging tissues. Ideally, they would have a programmable shape, which would allow them to adapt continuously to the environment encountered. At the same time, these robots need to be soft enough to prevent failure when reaching the target areas and/or doing some in situ manipulation in medical treatments, if it is the case. The materials used should be biocompatible and easy to integrate functional materials, i.e., materials with a function of diagnostics or therapeutics⁷. As potential functionalities are thermal action for localized cancer treatment, hyperthermia, or cauterization of wounds; micro-gripping for non-invasive micro-biopsies and drug loading, for targeted drug delivery. In the case of microscale grippers/tweezers, if the stiffness of the microgripper could be reversibly and actively tuned would be a plus. It would be soft until reaching the target area, stiffened for actuation and return to its initial soft properties to be removed from the body⁷.

Figure 2. Left: Microgripper in the relaxed and actuated state. Right: Inverted microgripper mechanism in the relaxed and actuated state. Scale bars: 100μm⁸.

In this line of thinking, a group at EPFL, in Switzerland, developed different prototypes of microgrippers (Figure 2) that can be wirelessly actuated with light (see live actuation in the following video). These microgrippers could be potentially integrated with catheters for micro-biopsies, or simply used in the laboratory for microscale manipulation and transport of soft samples, such as cells, tissues, organoids or soft materials as is the case of hydrogels⁸,⁹.

Very briefly, the group used a microfluidic system to generate droplets with active nanoparticles, that subsequently will be cross-linked, resulting in a microsphere that can be actuated with light, i.e., upon light activation, these spheres can shrink, and swell when the light is switched off. This contracting/swelling property was used in analogy to the muscle contraction as a source of force. When connected to a skeleton, in this case, photopolymerizable hydrogel PEGDA, one can fabricate various tools that will be controlled with light, hence wirelessly.

Figure 3. Compression of a spheroid of cells. Scale bar: 100μm⁸.

Besides the microgripper, the group also fabricated a soft-robotic compression device, Figure 3, to apply mechanical forces to 3D biological samples, being those, cell clusters, tissues or organoids; or even to measure their mechanical properties if a flexible probe is incorporated in the system⁸.

The fact that the skeleton of these structures is photopolymerizable, permits their fabrication directly inside lab-on-a-chip devices. This opens up the potential for the commercialization of new microfluidic devices for biomechanical studies and mechanical characterization of in vitro or ex-vivo biological samples⁸.

Final and briefly, the potential use of soft robots for drug delivery as an alternative to conventional systems is a very discussed topic. Target specific drug delivery still has a long way ahead before its commercial use, since: “Conventional drug delivery systems face several issues in medical applications, such as cyto/genotoxicity and off-targeting.”(Lucie Reinisová and colleagues)¹⁰ The use of soft-micro/nanorobots that can self-propel and navigate autonomously in fluids have a lot of potential. These small robots can hypothetically convert any external energy (chemical, ultrasounds, photo-electromagnetic fields) into motion. They can potentially have a higher cargo loading; precise targeting and on-demand release of the drugs, hence, reducing systemic side effects of highly toxic drugs¹⁰,¹¹.

Featured image credit: Nebahat Yenihayat

<sup>1. Development of Miniaturized Walking Biological Machines; Vincent Chan, et.al; Scientific reports, 857, 2012

2. Phototactic guidance of a tissue-engineered soft-robotic ray; Sung-Jin Park, et.al; Science, vol 353, July 2016

3. An integrated design and fabrication strategy for entirely soft, autonomous robots; Michael Wehner et.al., Nature Letter, vol 536, Agust 2016

4. Programmable soft robotics based on nano- textured thermos-responsive actuators. Dong Jin Kang, et. Al., Nanoscale, 11, 2019

5. Soft Robotic grippers; Jun Shintake, et.al.; Advanced Materials Review; 30, 2018

6. Soft Robotics for Chemists; Filip Ilievski, et.al; Angew. Chem.; 50; 2011.

7. Miniature soft robots-road to the clinic; Metin Sitti; Nature reviews; 2018

8. Modular soft robotic microdevices for dexterous biomanipulation; Berna Özkale, et.al.; Lab on a Chip; 2019

9. Universal Soft Robotic Microgripper; Haiyan Jia, et.al; Small; 2018

10. Micro/nanomachines: what is needed for them to become real force in cancer therapy; Lucie Reinisová, et.al.; Nanosacle; 2019

11. Micro/Nanorobots at Work in Active Drug Delivery; Ming Luo; Advanced functional materials, 28, 2018</sup>

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Raquel Parreira

Raquel Parreira is currently doing a Ph.D. in Bioengineering and Biotechnology at EPFL in Lausanne, Switzerland and she did her studies in the field of Biological Engineering at IST in Lisbon, Portugal. Her main focus is developing a variety of mechanically actuated systems for mechanobiology studies, for example, engineered biopolymers for in situ local mechanical stimulation and micro-soft robotic tools as the microgrippers and compressors recently published in Lab-on-a-Chip journal.

• raquelfparreira@hotmail.com

The post Micro-Soft-Robots are Already Here: Future Commercial Prospect appeared first on The MicroFluidic Circle.

From the economic perspective, the adoption of new technologies must be easily adaptable and cost-effective, unfortunately, these two requirements have not been properly met. Most publications regarding microfluidics are found mostly in engineering journals¹ or in patent form², thus limiting an immediate adoption due to their complexity. However, it’s not to say that microfluidics adoption is not on its way as applications range from chemical synthesis of organics, inorganics polymer particle as well as in emulsions, microencapsulation, steam reforming³ and biochemistry in high-throughput formats². Additionally, part of the easy adoption of microfluidics by industry is to address the technical problem of the complexity of scalability in which complex flow distribution and intricate reaction detection methods are required³,⁴. This latter issue mostly affects large-scale applications of microfluidic reaction technology.

As mentioned before, microfluidic technology must be cost-effective to be feasible, and this must be straightforwardly met when costly and delicate reagents are involved. The obvious advantages provided by microfluidics of small-volumes and precise liquid handling² can provide cost-effective high throughput biochemical assays and diagnostics³. However, to widely implement these technologies, portability, miniaturized and stand-alone lab-on-a-chip devices are still needed². Nevertheless, this remains a largely an unfulfilled vision of the microfluidics community.

Fig. 1. An analogy of the technological development to the modern computer. The blue colour indicates the current transition in technology progress.

To understand the current technological state of microfluidics, I can make an analogy to the history of the digital computer. In my opinion, we are seeing a transition in the technological development of microfluidics where advanced microfluidic chips are now being incorporated into laboratory equipment (Fig. 1). And as mentioned before, such applications are finding their niche in biochemical assays and diagnostics. Once, such device integration is widely adopted, we can expect a fast improvement of multifunctional and high-throughput microfluidics platforms.

Indeed, microfluidics has a large potential to be integrated into powerful platforms. However, the exact timeline of microfluidics fully reaching the consumer market is still hard to predict as it will depend on the demand of small volume handling, cost feasibility based on the application and the technical aspects of the scalability.

<sup>1. Caicedo, H. H.; Brady, S. T. Microfluidics: The Challenge Is to Bridge the Gap Instead of Looking for a ‘Killer App.’ Trends Biotechnol.2016, 34 (1), 1–3.

2. Chiu, D. T.; deMello, A. J.; Di Carlo, D.; Doyle, P. S.; Hansen, C.; Maceiczyk, R. M.; Wootton, R. C. R. Small but Perfectly Formed? Successes, Challenges, and Opportunities for Microfluidics in the Chemical and Biological Sciences. Chem2017, 2 (2), 201–223.

3. Elvira, K. S.; i Solvas, X. C.; Wootton, R. C. R.; deMello, A. J. The Past, Present and Potential for Microfluidic Reactor Technology in Chemical Synthesis. Nat. Chem.2013, 5 (11), 905–915.

4. Amador, C.; Gavriilidis, A.; Angeli, P. Flow Distribution in Different Microreactor Scale-out Geometries and the Effect of Manufacturing Tolerances and Channel Blockage. Chem. Eng. J.2004, 101 (1–3), 379–390.</sup>

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Adrian Zambrano

Adrian Zambrano is a scientist at the Max Planck Institute of Molecular Cell Biology and Genetics in Germany where he synthesizes protein/polymer scaffolds for micro-droplets and utilizes microfluidics for the encapsulation of enzymatic DNA replicators and other DNA-based assays. He holds a Ph.D. in physics from the University of Paris-Saclay/CNRS and B.Sc. in chemical engineering from the University of Nevada, Reno. His personal interests lie in the commercialization and development of high-throughput assays based on microfluidic technology.

• adrianzamphd@gmail.com
• https://sites.google.com/view/adrianzambrano/

The post Why Hasn’t Microfluidics Reached Consumer Market Despite a Huge Number of Academic Inventions and Publications During the Past 15 Years? appeared first on The MicroFluidic Circle.

In Japan, cancer researchers are building microfluidic chip cell sorters for capture and analysis of Circulating Tumor Cells (CTC), an endeavor that historically has ranged from challenging to impossible. Their “On‐chip Sort” detected and captured rare CTCs from patients with lung adenocarcinoma, which have typically been undetectable. Mutation detection using isolated CTCs is their next goal.

Austrian scientists at Vienna’s Institute of Molecular Biotechnology are creating lab-grown brain organoids. Brain tumors’ thickly tentacled structure makes them hard to remove surgically. Molecular characteristics make it difficult to map the winding journey that cancers travel. Glioblastoma in particular links up with blood vessels, feeding cancer cells to grow and spread quickly.

IMBA researchers report that their organoids-in-a-dish allow them to replicate carcinogenesis. They can observe onset at early stages, and monitor the tumor growing, in ways previously not possible. Their neoplastic organoids reproduce unique neural aspects, such as an array of cell types and development stages. This provides a way to see how tumors arise. The Vienna researchers can also test different therapies in the dish.

At Griffith University in Queensland, Australia, scientists are investigating micro-optofluidics and micro-magnetofluidics. Micro-optofluidics engineers explore the interaction between fluid flow and light, for new applications. The combination of magnetism and fluid flow reveals the path toward research into micro-magnetofluidics.

In the U.S., researchers at Texas Technology are growing artificial corneas-on-chips to measure how much eye medication reaches its target. This is commonly tested utilizing rabbit eyes. The Texas scientists’ aim to reduce the use of animal testing for eye medication.

“Nobody knows how much eye medicine is really released into the eye because of certain barriers,” one of the researchers explained. “The first barrier is the cornea. The cornea itself is made up of five layers of cells. Companies usually use rabbit eyes because of structural similarity with slow blinking speed.” However, such tests don’t replicate the process inside the of the human cornea. The corneas-on-chips mimic corneal constraints, enabling realistic analyses of permeability.

Researchers in Massachusetts developed a microfluidic assay that detected sepsis infection from just one drop of blood. Sepsis is potentially fatal. Sepsis develops from lesser infections, when infection-fighting processes trigger inflammation that can damage organs, causing them to fail. Prompt diagnoses and early treatment increase the survival rate. The mortality rate for septic shock is nearly 50 percent.

Quick diagnosis is crucial because sepsis symptoms are typical of other disorders. Multiple assessments are sometimes needed, including heart rate and respiration rate; blood tests; X-rays, ultrasound, MRIs or CT scans; liver/kidney function tests and electrolyte imbalances. The assessment might mean obtaining data from multiple unconnected sources. Electronic systems that link data together, and automatically analyze and monitor information, facilitate quick treatment. But they can fail, resulting in false positive or false negative indications.

So an uncomplicated method of diagnosis, with one drop of blood, would be not only striking but life-altering. The researchers’ “assay identified sepsis patients with 97 percent sensitivity and 98 percent specificity,” they reported.

And then there’s deep space. Minus the constraints of gravity, astronauts learn the limits of physiology in space, as well as the limits of the earthly-made equipment. In case they need tools customizable for unanticipated tasks, 3D printing technology is now onboard the International Space Station, or ISS.No need to return all the way back to Earth for that special wrench. In addition to 3D printing of tools, research is underway into the possibility of biofabrication in space. Investigation of cellular function in space shows organoids may have a role in 3D bioprinting, for organ replacement during deep space travel.

So there might be no need to return all the way back to Earth for that wrench — or that medical treatment either.

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Kathy Jean Schultz

Kathy Jean Schultz is a freelance medical science writer who focuses on medical innovations. She earned a Master’s Degree in Research Methodology from Hofstra University, and a Master’s Degree in Psychology from Long Island University. She is a member of the National Association of Science Writers, and the Association of Health Care Journalists. Her articles about organoids include "Would you trust a 3-D printed mini organ to test your drugs?" and "Stem cells not only slow disease, they come with their own safety test".

• http://kathyjeanschultz.pressfolios.com/

The post Recent Microfluidics Advances, on Earth and Above It appeared first on The MicroFluidic Circle.

Microfluidics in Biology

Microfluidics is one such technology that has demonstrated great potential in reducing the time and cost of conventional laboratory assays. Briefly, microfluidics is the control of fluids in channels at the scale of tens to hundreds of micrometer. As a result of the small scale at which the fluids are processed, the flow is typically laminar (Reynolds number <100) and can be controlled very precisely. Given that most biological samples contain thousands to millions of cells to be analyzed and can be relatively hard to collect, microfluidics is especially suited for biological work as it allows for high throughput processing with only a small amount of sample.

The idea of Lab-On-a-Chip (LOC) using microfluidic technology is to integrate current and novel research principles into a single miniaturized device in the nano- to micro-scale. However, it is noteworthy that the idea of microfluidics is not entirely recent. Fluid manipulation in microchannels has been around since the 1950s. However, the field centered around devices fabricated using integrated circuit technology limited to silicon substrates, while taking advantage of the electroosmotic flow to manipulate their targets. With the emergence of softer materials and advanced fabrication techniques in the 1990s, microfluidics gained widespread popularity amongst biologists and engineers¹. From cell-based assays², genomics³, proteomics⁴,⁵, transcriptomics⁵ and even drug discovery⁶, microfluidics have branched out in many disciplines of biological sciences. Microfluidic technology can be further categorized into two classes, employing either active sorting or passive (label-free) sorting methods to control targets. With the advancement in microfluidics, the analyses of individual cells are now a possibility.

1. The Need for Single Cells
In many scientific studies, bulk data are often used as a representation to interpret results. However, the major drawback of this technique is the possible heterogeneity within populations. One well-researched example is circulating tumour cells (CTCs) present in the blood of metastatic cancer patients.  CTCs are tumor cells that disseminate into the bloodstream from the primary tumor to begin the metastasis process. Although most tumour cells in circulation do not survive the hostile immune environment and high shear experienced in blood vessels, some CTCs do successfully travel and establish at a distant site to form a metastatic lesion. While whole blood can be obtained using liquid biopsy, a non-invasive technique, the extremely low numbers of CTCs (1-10/mL) would mean taking the average from whole blood would likely arrive at results biased towards wild-type readings such as white blood cells. Moreover, due to the low numbers of these cells, the genetic information may also be masked. Microfluidics has enabled the fractionation and isolation of CTCs. Through this, genomic analysis can be conducted at the individual cell level which can reveal critical information about the mutational status of the cancer patient. This would then allow clinicians to personalize treatment and improve the survival in these patients.

Figure 1. A microfluidic single cell isolation device. Image adapted and reproduced with permission from Yeo et al., Sci. Rep. 6, 22076 (2016). Copyright Nature Publishing Group.

2. Portability
In developing countries, infectious diseases are a widespread problem for people and economic development. This situation is worsened by a lack of well-equipped diagnostic laboratories. The usual detection by molecular assays such as the enzyme-linked immunosorbent assay, western blotting and PCR requires skilled technicians and several hours of processing.  Therefore, a potential solution is to have a portable point-of-care (POC) device providing rapid detection. Particularly, one emerging technique, involving the use of paper microfluidics, has shown promise in the detection of pathogens such as HIV with minimal steps⁷. Paper microfluidics have also been deployed successfully in the field to detect Ebola⁸. The low fabrication cost, diverse capabilities and small size of microfluidic devices make them suitable for POC diagnostics. In particular, paper microfluidics eliminates the need for a laboratory and its bulky equipment in order to perform these tests.

Outlook

Globally, labs are pushing the boundaries of engineering and biology. Aside from its apparent portable size, additional advantages of microfluidics are as follows:

• Flexibility in manipulation
• Lower reagent
• Affordability
• Real-time monitoring

There are other numerous physical phenomena used in fluid dynamics. Aside from paper-based methods, there are also the following methods which are commonly used,

• Droplet microfluidics
• Digital microfluidics
• Sensor microfluidics
• Optofluidics

With countries transitioning from basic to translational research, the integration and collaborations across different expertise are pivotal. Nevertheless, despite the increasing numbers of microfluidic-related publications, few devices end up being commercialized. One barrier to this is the automation of microfluidic devices requires shrinking of concomitant components. Another pressing issue is a need to prevent ephemeral graduate projects by encouraging aspiring scientists to collaborate with industries and clinicians and identify a market need and to go further by developing the device for commercial use. The pressure of looking for a novel method for publication means students spending years working on a design from conception instead of developing and optimizing a pre-existing one.

That being said, the diversity of research in microfluidics can also generate better ideas and competition may drive breakthrough projects. As compared to conventional lab-bench equipment, the higher throughput seen in microfluidics means obtaining results in a shorter time coupled with higher spatial and temporal resolution. Already, with the advancement in microfluidics, we are moving towards a minimally invasive tool for cancer assessment and detecting pathogens in resource-limited areas. Hopefully, in the near future, we will develop a POC device which can provide a rapid health analysis from the comfort of our homes without the need for long waits at the hospital. Microfluidics is revolutionizing the way experiments are performed by transferring the diagnostic capabilities from lab bench to consumer’s hands, and it may continue to complement research in science in unprecedented ways.

<sup>1. Duffy, D.C., et al., Rapid Prototyping of Microfluidic Systems in Poly(dimethylsiloxane). Anal Chem, 1998. 70(23): p. 4974-84.

2. Tumarkin, E., et al., High-throughput combinatorial cell co-culture using microfluidics. Integr Biol (Camb), 2011. 3(6): p. 653-62.

3. Kim, S., et al., High-throughput automated microfluidic sample preparation for accurate microbial genomics. Nature Communications, 2017. 8: p. 13919.

4. Abdel-Sayed, P., et al., Fabrication of an Open Microfluidic Device for Immunoblotting. Analytical Chemistry, 2017. 89(18): p. 9643-9648.

5. Genshaft, A.S., et al., Multiplexed, targeted profiling of single-cell proteomes and transcriptomes in a single reaction. Genome Biology, 2016. 17(1): p. 188.

6. Tsui, J.H., et al., Microfluidics-assisted in vitro drug screening and carrier production. Advanced Drug Delivery Reviews, 2013. 65(11): p. 1575-1588.

7. Rohrman, B.A. and R.R. Richards-Kortum, A paper and plastic device for performing recombinase polymerase amplification of HIV DNA. Lab on a Chip, 2012. 12(17): p. 3082-3088.

8. Magro, L., et al., Paper-based RNA detection and multiplexed analysis for Ebola virus diagnostics. Scientific Reports, 2017. 7(1): p. 1347.</sup>

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Trifanny Yeo

Trifanny Yeo is currently a research assistant at the Department of Biomedical Engineering, National University of Singapore. She received her BSc from the University of Queensland and has been working with microfluidics, developing devices for use in personalized medicine. Her research interest also includes transcriptomics, nanomaterials and wearable electronics.

The post How Did Microfluidics Change Biological Research? appeared first on The MicroFluidic Circle.

In one sense, organ on a chip devices are becoming more complex, as evidenced by the March 2018 announcement of an organ on a chip device that can model up to 10 organs and their interactions for a continuous 1 month run². In another sense, organ on a chip models are still very simplistic, as they don’t yet feature the multi-tissue structure that defines an organ. Most organ on a chip applications feature a channel or chamber in which cells are cultured, and interact with various factors, such as a liquid phase flowing adjacent to the cells, which simulates blood flow around the tissue³. However, the name “organ on a chip” paints a very different picture. A lay person who hears this term would never picture the relatively simple devices which are used today. This is where it may be worth examining organ on a chip as a PR case study for scientists.

With the increasing scientific use and commercialization of lab on a chip devices in general, it is likely that in a few years the terms “lab on a chip” and “organ on a chip” will become familiar to the general public. At that point, the name “organ on a chip” will present a problem because “organ on a chip” paints a vivid picture, but that picture is very inaccurate, and a little alarming. Many may think that these devices include full organs that are connected to some sort of chip, maybe an electronic one. Currently, the only people who have heard of this technology have read something about it. Once “organ on a chip” is a household term, it must be expected that there will be a portion of the public who have heard of the term but have no idea what it looks like, or what it does.

In that case, organ on a chip technology may face unnecessary opposition from the public, who do not want lab experiments that use human or animal organs. The myth that artificial organs are grown on chips may come about. Artificially making organs is a controversial idea that has faced ethical or religious objections, with 23% of Americans reported to oppose bioengineered organs for medical use in a 2015 report⁴. Of course, these objections have nothing to do with the actual organ on a chip technology, but it is possible that Organ on a chip researchers face them anyway from a public who is misled by the evocative name of the technology.

Cloning and stem cell technologies have faced similar problems before. Some of the objections to these technologies have come from myths about them, such as cloning technology being used to fully replicate an adult⁵. Could organ on a chip also face public opposition based on a misunderstanding of what it really is?

It is possible. First, organ on a chip would have to become a commonly recognized term. This is likely to happen as exciting breakthroughs continue to get news coverage. At that point, some people will likely associate the term with artificial organs and could oppose the idea. Whether such opposition would get any momentum may not be so much up to the scientific community. For example, if an influential TV personality started to denounce it, organ on a chip could be a hot topic. Unfortunately, some technologies are criticized or opposed based on perceived issues that are not in line with reality.

What about legislation and politics? In the US, stem cell research has been restricted or banned in many states, and federal funding for it has been restricted in the past. GMOs are heavily regulated around the world as well. However, major political resistance against organ on a chip devices are not likely, even if the public perceives the same problems with organ on a chip devices. This is because stem cell research and GMOs are very clearly defined in terms of the techniques involved. Stem cell legislation has usually defined its scope specifically based on whether embryos are involved, and how they are obtained⁶. In the case of an organ on a chip, there is not a specific technique or process step that could be targeted by legislation. It is simply a new configuration for in vitro models and microfluidic devices. This points to another reason serious opposition may never happen –would be leaders of activism against organ on a chip would first find out more about organs on a chip, and learning more about the technology could dissuade most from opposing it.

Where would this leave a potential controversy? There may or may not be a short time of 1-2 years where organs on a chip become well known, and then become a hotly debated technique. The vicissitudes of politics and media would be a big, unpredictable factor there. A lasting stigma is not likely; organs on a chip would be just another technology that some people really misunderstand. However, there is a takeaway for the scientific community. There is a lesson on managing the message and the image here, and the importance of names is obvious. By picking this very evocative, but misleading name, have we invited trouble? Will we later have to correct myths, be opposed by the public and spend our time answering nonsensical questions?

Should we have purposefully picked a different name? Should we look for an alternative now? Probably not, but it is good to think about the subject. What we should do in the future is to think from this marketing perspective every now and then, especially when coining a new term, or announcing a breakthrough. Scientists have the most control over the message when they are reporting their work – until they announce it, the world does not know about it. We should take advantage of that moment.

<sup>1. Funk, C., 2017. “Real Numbers: Mixed Messages about Public Trust in Science.” Issues in Science and Technology, 34(1), 86-88.

2. Hamzelou, J., 2018. “Miniature organs mimic human body.” New Scientist 27(3170), 1025-1031.

3. Bhatia, S. N., Ingber, D. E., 2014. “Microfluidic organs-on-chips.” Nature Biotechnology 32(8), 760-772.

4. Funk, C., Raine, L., Page, D., 2015. “Americans, politics and science issues.” Pew Research Center.

5. Miller, R. G., 2006. “Cloning: A critical analysis of myths and media.” Science Scope, 29(6), 70-74.

6. Pew Research Center, 2001. “Human Cloning: Religious Perspectives.” http://www.pewforum.org/2001/05/03/human-cloning-religious-perspectives/ (See Mr. Wasinger’s comments)</sup>

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Aytug Gencoglu

Aytug Gencoglu has a decade of microfluidics experience, primarily in academic labs. He has previously published articles on electrode deterioration, pH changes in microfluidic channels, and dielectrophoresis, and developed microfluidics components for dielectrophoretic cell characterization.

• aytuggencoglu@outlook.com

The post Scientists Should Think Like Marketers: The Organ on a Chip Case appeared first on The MicroFluidic Circle.

Scientific research was never meant to stay on papers. Just as Lab-on-a-Chip devices true destiny is in poor communities in developing countries. Academics all around the world have worked with a Lab-on-a-Chip concept, imagining that the power of a state-of-art laboratory could fit in their pocket. Contrary to popular belief, engineers and scientist are highly creative people, otherwise, they wouldn’t be able to imagine complex micro-manufacturing of chips to make health testing easier.

Jules Verne, a French author, image a vehicle that could go underwater in “Twenty Thousand Leagues Under the Sea.” Years later, visionary scientists were able to make a submarine made true. The military industry propelled this and other innovations, but after the war, they have been able to serve in deep oceans explorations. Today’s battles are not fought on fronts but with corruption and poverty.

Prof. Marc Madou from University of California, Irvine and Dario Mager from KIT university showing a lab-on-a-CD. Credit: Monica Arreola

Lab-on-a-Chip is both a device and a sensor. By being a device the size of a human palm, transportation is made easier. But in order to work as a laboratory, sensors need to be attached to the micro canals of the device. Inspiration à la Verne was what made Marc Madou build a Lab-on-a-Chip in the size of a CD-Rom. The professor of University of California, Irvine and of Tecnológico de Monterrey (Mexico) realized that while predecessors have managed to create the device and the sensors, there was still a need to analyze the results of the tests.

Madou, along with his graduate students and fellow researchers managed to send information from a Lab-on-a-Chip to a nearby health center using a portable CD player. The shape of the Chip and the rotation of the once-popular music device was ideal to test a human being for multiple diseases while using one drop of blood. Taking this device to villages in Mexico and India that do not have a health clinic, Wi-Fi or electricity could be the answer to reducing infant related deaths.

Why hasn’t Lab-on-a-Chip become available already? According to professor Madou and his team in KIT (Germany), Tec (Mexico) and UCI (USA) is because each prototype takes money. Funding research is not as sexy or popular as funding Start Ups, but maybe the solution to a lot of the society’s issues. A win-win tactic that young researchers have taken is to make the devices as cheap and ecological as they can.

Prof. Roberto Gallo from Tec de Monterrey university showing prototypes of a lab-on-a-chip to American visitors. The Microfluidics Laboratory is run by Prof. Gallo and his colleagues of the Sensors and Devices research group. Credit: Monica Arreola

Lab-on-a-Chip can be created using biodegradable materials, for instance, carbon, that can be disposed right after its use. Also, the scientific community is investing in advanced materials to reduce device weight. If the Lab-on-a-Chip is easy to carry, then it can reach remote villages and populations without roads. Another key factor is the cost, doing two to four tests with one chip can abruptly reduce the investment in health care. And if the device costs less than a dollar the possibilities of reducing death by diarrhea in India and by diabetes in Mexico grow exponentially.

With the multi-factors explained above it becomes evident that the task of making Lab-on-a-Chip an everyday device is not easy. However, putting an emphasis on universal health care can be a daily fight. The current administration in the United States has underestimated and underfunded several health care programs. The impact on American citizens and refugees has been dramatically evident. The indirect impact of this thinking trend has permeated in the neighboring countries.

Mexico has a universal health care system for all citizens. Most procedures and medicines are free of charge while the rest is subsidized by the central government. Such a system offers a safety net for the poorest populations and larger families. This system is not enough. Doctors are overworked, lines for medicines and appointments can take hours, and the aisles can be full of patients on their way to surgery. A way to ease these issues can be with the help of devices, sensors, and software that are cheap and effective.

Lab-on-a-Chip is a promise made to humanity. And the only way of making it a reality is to debunk the myth that health is a privilege.

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Mónica Arreola

Mónica is a Public Relations professional and blogger. Over the course of the years, she has tackled topics as like violence and art in Latin America, scientific research, gender equality, and education trends. She holds a BA in International Relations (2013) and an MBA (2017). In 2017 she published her first ebook "Dobleletra" a series of poems in her native language, she is currently working on her second title “Sueñosmundanos.” Mónica creates editorial content for her academic job, but she switches gears doing standup, yoga, feminist blogging in Café Curie, and walking her baby dog, Nina .

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