In 2022, the <a href="https://www.imseam.uni-heidelberg.de/en" target="_blank" rel="noopener" id="isPasted">Institute for Molecular Systems Engineering and Advanced Materials (IMSEAM)</a> was established at Heidelberg University, the oldest university in Germany, founded in 1386. &nbsp;The mission of the IMSEAM is to create new materials, methods and technologies from synthetic and natural building blocks at the molecular level, considering complete systems from molecule to function. Four research groups and two junior research groups are currently working at IMSEAM on basic principles and applications for materials development, organic electronics, environmental technology and medicine. IMSEAM also offers core facilities in the field of device fabrication and characterization (IMSEAM core Facility), soft (bio) materials characterization and microfluidics for other university groups.<h2 id="isPasted">Scientific Facility for Microfabrication and Microfluidics</h2>Microfluidics is an emerging field and is finding use in various disciplines. Starting from understanding flow mechanisms, to the generation of synthetic cells with droplet-based microfluidics, continuous flow microfluidics to complex organ-on-a-chip models. The Microfluidics Core Facility (µFlu CF) aims to provide this valuable tool to every interested research group at the University. For example, researchers are supported with contributions to project design, the production of microfluidic chips and the implementation of experiments in biosafety laboratories. “In May 2022, we began procuring the first instruments for the production and analysis of microfluidic chips,” reports Dr. Sadaf Pashapour, project manager of the Core Facility. Traditionally, photolithography is used to create a master wafer on a photoresist-coated silicon wafer. A maskless aligner that can produce 2D geometries with 1 to 200 µm in height was procured for this purpose. In addition, the height of the generated structure must be measured with an interference profilometer. The difference in height between the silicon wafer and the exposed photoresist lies within a measuring range of 1 µm to 2-3 mm. “In addition to this process, however, we also wanted to be able to produce 3D geometries,” says Dr. Pashapour. “That’s why we looked around for a suitable 3D printer.”<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1728284454427-microArch-S140_10mSeries-2.jpg" style="width: 100%px;" class="fr-fic fr-dib">microArch S140: BMF’s 10µm series 3D printers offer a level of precision and accuracy that delivers the most challenging micro parts at production quality.<h2 id="isPasted">Decision in favor of PµSL technology</h2>After extensive market research, a typical design was selected and sent to four or five suppliers. “For us, the challenge is to print narrow channels with the smoothest possible walls so that there is no turbulence later on”, Dr. Pashapour explains. “Only BMF was able to produce the sample part perfectly.” The company has developed <a href="https://bmf3d.com/introduction-to-3d-printing-with-projection-micro-stereolithography/" target="_blank" rel="noopener">projection micro stereolithography (PμSL)</a> to achieve the right resolution, accuracy and precision for micro production. As a form of stereolithography (SLA), it requires a digital light processing engine (DLP), precision optics, high-precision motion control and associated software. As with SLA, components are broken down into layers and projected onto liquid, photosensitive resin using a light source. Polymer cross-linking and solidification takes place at the exposed areas. With PμSL technology, an ultraviolet (UV) flash of light causes the rapid photopolymerization of an entire resin layer. Continuous exposure is used to ensure faster processing. Based on this technology, BMF offers 3D printing platforms with different resolutions: The top model microArch S230 achieves an optical resolution of 2µm with a layer thickness of 5µm to 20µm. “For budget reasons, however, we opted for a microArch S140, a desktop model with 10µm resolution,” says Dr. Pashapour. “This incredible device produces very good results.”<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1728284486289-UH-200%C2%B5m-chambers.jpg" style="width: 100%px;" class="fr-fic fr-dib">Chambers: Trapping of organoids in a 200µm wide chamber with 100µm flow inlets of both sides from the chamber<h2 id="isPasted">Installation and introduction</h2>The microArch S140 offers sufficient build space of 94 x 52 x 45 millimeters. The platform is material-open – not only the materials offered by BMF can be used, but also suitable products from third-party suppliers. &nbsp;In contrast to other manufacturers, BMF also allows extensive intervention in the printing parameters so that users can achieve the desired results under optimal conditions. After the installation, BMF offered a comprehensive introduction: “The introduction was carried out step by step for a whole week and the entire theory behind the device was explained very well, so we really understand all functions of the printer,” says Dr. Pashapour happily. “When I wanted to print my first projects, I received support in a messenger group. They responded really quickly there.” The microArch S140 has now been working around the clock since September 2023 – except for a Christmas break. Since then, Dr. Pashapour has had to change the membrane once and received an online course.<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1728284529750-1728284529749.png" class="fr-fic fr-dib"><h2 id="isPasted">Best results at the cutting edge of research</h2>In the meantime, word of the new possibilities of the Microfluidics Core Facility has spread beyond the campus. Around 20 researchers have already worked on projects here right through to the finished chip. Collaborations now exist with the Technical University of Munich, the Leibnitz Institute in Saarbrücken and as far away as Chile. The printer works day and night all week. “I operate the printer alone so that I can assign priorities correctly,” says Dr. Pashapour. “While the printer is running, I can prepare new projects, rework components or pursue my other tasks.”The ability to print directly onto a glass substrate with the yellow resin is particularly valuable. “The better view allows us to better analyze the microfluidic processes,” says Dr. Pashapour. “However, we would like to have software support for the micron-precise alignment of the glass plate on the build plate – we now use calipers for this.” Various other projects, from cubes with 150µm cavities to 3D-printed micro-wells with a diameter and depth of 80µm and a spacing of 20µm to 100µm fine grids for cell-induced deformations, have been successfully completed. “The S140 meets our requirements for accuracy and precision every time – the surfaces become just as smooth as we need them to be,” says Dr. Pashapour. In addition to solid resin, she would also like to use elastic materials, for example for a synthetic lung as an “organ on a chip”. At first, one design was too complex for the 3D printer. “We have sent it to the support team at BMF,” explains Dr. Pashapour. “Maybe the 100 micrometer struts can be realized with the 2µm printer.”

The Microfluidics Core Facility at Heidelberg University successfully uses the 3D printing technology of projection micro-stereolithography (PµSL) from BMF. Sophisticated research projects are supported with microparts such as microwells, various microfluidic devices and “organs-on-a-chip”.

How 3D printing propels microfluidics at IMSEAM at the University of Heidelberg

In this episode, discuss how big of a problem lead contaminated water still is across the world and how a collaboration between MIT & Nanyang University plans to tackle it with a highly accurate and inexpensive water pollution sensor.

Podcast: Is Your Drinking Water Safe? This Sensor Has The Answer

Researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed a programmable metafluid with tunable springiness, optical properties, viscosity and even the ability to transition between a Newtonian and non-Newtonian fluid.&nbsp;The first-of-its-kind metafluid uses a suspension of small, elastomer spheres — between 50 to 500 microns — that buckle under pressure, radically changing the characteristics of the fluid. The metafluid could be used in everything from hydraulic actuators to program robots, to intelligent shock absorbers that can dissipate energy depending on the intensity of the impact, to optical devices that can transition from clear to opaque.The research is published in <a href="https://www.nature.com/articles/s41586-024-07163-z" target="_blank">Nature</a>.&nbsp;“We are just scratching the surface of what is possible with this new class of fluid,” said Adel Djellouli, a Research Associate in Materials Science and Mechanical Engineering at SEAS and first author of the paper. “With this one platform, you could do so many different things in so many different fields.”<blockquote>"We are just scratching the surface of what is possible with this new class of fluid. With this one platform, you could do so many different things in so many different fields."ADEL DJELLOULI, RESEARCH ASSOCIATE IN MATERIALS SCIENCE AND MECHANICAL ENGINEERING</blockquote>Metamaterials — artificially engineered materials whose properties are determined by their structure rather than composition — have been widely used in a range of applications for years. But most of the materials — such as the metalenses pioneered in the lab of <a href="https://seas.harvard.edu/person/federico-capasso" target="_blank">Federico Capasso</a>, Robert L. Wallace Professor of Applied Physics and Vinton Hayes Senior Research Fellow in Electrical Engineering at SEAS — are solid.&nbsp;“Unlike solid metamaterials, metafluids have the unique ability to flow and adapt to the shape of their container,” said <a href="https://seas.harvard.edu/person/katia-bertoldi" target="_blank">Katia Bertoldi</a>, William and Ami Kuan Danoff Professor of Applied Mechanics at SEAS and senior author of the paper. “Our goal was to create a metafluid that not only possesses these remarkable attributes but also provides a platform for programmable viscosity, compressibility and optical properties.”Using a highly scalable fabrication technique developed in the lab of<a href="https://seas.harvard.edu/person/david-weitz" target="_blank">&nbsp;David A. Weitz</a>, Mallinckrodt Professor of Physics and of Applied Physics at SEAS, the research team produced hundreds of thousands of these highly-deformable spherical capsules filled with air and suspended them in silicon oil. When the pressure inside the liquid increases, the capsules collapse, forming a lens-like half sphere. When that pressure is removed, the capsules pop back into their spherical shape.&nbsp;<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1712910643712-ezgif-6-525a83ddd2.gif" style="width: 100%px;" class="fr-fic fr-dib">When pressure is removed from the fluid, the capsules pop back into their spherical shape. (Credit: Adel Djellouli/Harvard SEAS)That transition changes many of the liquid’s properties, including its viscosity and opacity. Those properties can be tuned by changing the number, thickness and size of the capsules in the liquid. &nbsp;The researchers demonstrated the programmability of the liquid by loading the metafluid into a hydraulic robotic gripper and having the gripper pick up a glass bottle, an egg and a blueberry. In a traditional hydraulic system powered by simple air or water, the robot would need some kind of sensing or external control to be able to adjust its grip and pick up all three objects without crushing them.&nbsp;But with the metafluid, no sensing is needed. The liquid itself responds to different pressures, changing its compliance to adjust the force of the gripper to be able to pick up a heavy bottle, a delicate egg and a small blueberry, with no additional programming.&nbsp;“We show that we can use this fluid to endow intelligence into a simple robot,” said Djellouli.The team also demonstrated a fluidic logic gate that can be reprogrammed by changing the metafluid.The metafluid also changes its optical properties when exposed to changing pressures.&nbsp;<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1712910829305-ezgif-6-15470cf979.gif" style="width: 100%px;" class="fr-fic fr-dib">Metafluid over the Harvard logo. (Credit: Adel Djellouli/Harvard SEAS)When the capsules are round, they scatter light, making the liquid opaque, much like air bubbles make aerated water appear white. But when pressure is applied and the capsules collapse, they act like microlenses, focusing light and making the liquid transparent. &nbsp;These optical properties could be used for a range of applications, such as e-inks that change color based on pressure.&nbsp;The researchers also showed that when the capsules are spherical, the metafluid behaves like a Newtonian fluid, meaning its viscosity only changes in response to temperature. However, when the capsules are collapsed, the suspension transforms into a non-Newtonian fluid, meaning that its viscosity will change in response to shear &nbsp;force — the greater the shear force, the more fluid it becomes. This is the first metafluid that has been shown to transition between Newtonian and non-Newtonian states.Next, the researchers aim to explore the acoustic and thermodynamic properties of the metafluid.&nbsp;“The application space for these scalable, easy-to-produce metafluids is huge,” said Bertoldi.Harvard’s&nbsp;<a href="https://otd.harvard.edu/" target="_blank">Office of Technology Development</a> has protected the intellectual property associated with this research and is exploring commercialization opportunities.The research was supported in part by the NSF through the Harvard University Materials Research Science and Engineering Center grant number DMR-2011754.&nbsp;It was co-authored by Bert Van Raemdonck, Yang Wang, Yi Yang, Anthony Caillaud, David Weitz, Shmuel Rubinstein and Benjamin Gorissen.

Researchers develop metafluid with programmable response

Intelligent liquid

Memory, or the ability to store information in a readily accessible way, is an essential operation in computers and human brains. A key difference is that while brain information processing involves performing computations directly on stored data, computers shuttle data back and forth between a memory unit and a central processing unit (CPU). This inefficient separation (the von Neumann bottleneck) contributes to the rising energy cost of computers.Since the 1970s, researchers have been working on the concept of a memristor (memory resistor); an electronic component that can, like a synapse, both compute and store data. But Aleksandra Radenovic in the Laboratory of Nanoscale Biology (<a href="https://www.epfl.ch/labs/lben/" target="_blank">LBEN</a>) in EPFL’s School of Engineering set her sights on something even more ambitious: a functional nanofluidic memristive device that relies on ions, rather than electrons and their oppositely charged counterparts (holes). Such an approach would more closely mimic the brain’s own – much more energy efficient – way of processing information.“Memristors have already been used to build electronic neural networks, but our goal is to build a nanofluidic neural network that takes advantage of changes in ion concentrations, similar to living organisms,” Radenovic says.“We have fabricated a new nanofluidic device for memory applications that is significantly more scalable and much more performant than previous attempts,” says LBEN postdoctoral researcher Théo Emmerich. “This has enabled us, for the very first time, to connect two such ‘artificial synapses’, paving the way for the design of brain-inspired liquid hardware.”The research has <a href="https://www.nature.com/articles/s41928-024-01137-9" target="_blank" rel="noopener">recently been published in Nature Electronics.</a><h2>Just add water</h2>Memristors can switch between two conductance states – on and off – through manipulation of an applied voltage. While electronic memristors rely on electrons and holes to process digital information, LBEN’s memristor can take advantage of a range of different ions. For their study, the researchers immersed their device in an electrolyte water solution containing potassium ions, but others could be used, including sodium and calcium.“We can tune the memory of our device by changing the ions we use, which affects how it switches from on to off, or how much memory it stores,” Emmerich explains.<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1712102720846-6b9cf0f3.jpg" style="width: 100%px;" class="fr-fic fr-dib">Illustration of a HAC circuit. 2023 EPFL/Andras Kis CC BY SA 4.0The device was fabricated on a chip at EPFL’s&nbsp;<a href="https://www.epfl.ch/research/facilities/cmi/" target="_blank">Center of MicroNanoTechnology</a> by creating a nanopore at the center of a silicon nitride membrane. The researchers added palladium and graphite layers to create nano-channels for ions. As a current flows through the chip, the ions percolate through the channels and converge at the pore, where their pressure creates a blister between the chip surface and the graphite. As the graphite layer is forced up by the blister, the device becomes more conductive, switching its memory state to ‘on’. Since the graphite layer stays lifted, even without a current, the device ‘remembers’ its previous state. A negative voltage puts the layers back into contact, resetting the memory to the ‘off’ state.“Ion channels in the brain undergo structural changes inside a synapse, so this also mimics biology,” says LBEN PhD student Yunfei Teng, who worked on fabricating the devices – dubbed highly asymmetric channels (HACs) in reference to the shape of the ion flow toward the central pores.LBEN PhD student Nathan Ronceray adds that the team’s observation of the HAC’s memory action in real time is also a novel achievement in the field. “Because we were dealing with a completely new memory phenomenon, we built a microscope to watch it in action.”By collaborating with Riccardo Chiesa and Edoardo Lopriore of the <a href="https://www.epfl.ch/labs/lanes/" target="_blank">Laboratory of Nanoscale Electronics and Structures</a>, led by Andras Kis, the researchers succeeded in connecting two HACs with an electrode to form a logic circuit based on ion flow. This achievement represents the first demonstration of digital logic operations based on synapse-like ionic devices. But the researchers aren’t stopping there: their next goal is to connect a network of HACs with water channels to create fully liquid circuits. In addition to providing an in-built cooling mechanism, the use of water would facilitate the development of bio-compatible devices with potential applications in brain-computer interfaces or neuromedicine.<hr>ReferencesEmmerich, T., Teng, Y., Ronceray, N. et al. Nanofluidic logic with mechano–ionic memristive switches. Nat Electron (2024). https://doi.org/10.1038/s41928-024-01137-9

Co-authors Nathan Ronceray and Théo Emmerich. 2023 EPFL/Titouan Veuillet CC BY SA 4.0

In a step toward nanofluidic-based neuromorphic – or brain-inspired – computing, EPFL engineers have succeeded in executing a logic operation by connecting two chips that use ions, rather than electrons, to process data.

Artificial nanofluidic synapses can store computational memory

3D-printed microscopic particles, so small that to the naked eye they look like dust, have applications in drug and vaccine delivery, microelectronics, microfluidics, and abrasives for intricate manufacturing. However, the need for precise coordination between light delivery, stage movement, and resin properties makes scalable fabrication of such custom microscale particles challenging. Now, researchers at Stanford University have introduced a more efficient processing <a href="https://doi.org/10.1038/s41586-024-07061-4" data-extlink="" target="_blank">technique</a> that can print up to 1 million highly detailed and customizable microscale particles a day.“We can now create much more complex shapes down to the microscopic scale, at speeds that have not been shown for particle fabrication previously, and out of a wide range of materials,” said <a href="https://profiles.stanford.edu/jason-kronenfeld" data-extlink="" target="_blank">Jason Kronenfeld</a>, PhD candidate in the <a href="https://desimonegroup.stanford.edu/" data-extlink="" target="_blank">DeSimone lab</a> at Stanford and lead author of the paper that details this process, published today in Nature.This work builds on a printing technique known as continuous liquid interface production, or CLIP, <a href="https://doi.org/10.1126/science.aaa2397" data-extlink="" target="_blank">introduced in 2015</a> by DeSimone and coworkers. CLIP uses UV light, projected in slices, to cure resin rapidly into the desired shape. The technique relies on an oxygen-permeable window above the UV light projector. This creates a “dead zone” that prevents liquid resin from curing and sticking to the window. As a result, delicate features can be cured without ripping each layer from a window, leading to faster particle printing.“Using light to fabricate objects without molds opens up a whole new horizon in the particle world,” said <a href="https://profiles.stanford.edu/joseph-desimone" data-extlink="" target="_blank">Joseph DeSimone,</a> Professor of Chemical Engineering in the <a href="https://engineering.stanford.edu/" target="_blank">School of Engineering</a> and corresponding author of the paper. “And we think doing it in a scalable manner leads to opportunities for using these particles to drive the industries of the future. We’re excited about where this can lead and where others can use these ideas to advance their own aspirations.”<h2>Roll to roll</h2>The process that these researchers invented for mass producing uniquely shaped particles that are smaller than the width of a human hair is reminiscent of an assembly line. It starts with a film that is carefully tensioned and then sent to the CLIP printer. At the printer, hundreds of shapes are printed at once onto the film and then the assembly line moves along to wash, cure, and remove the shapes – steps that can all be customized based on the shape and material involved. At the end, the empty film is rolled back up, giving the whole process the name roll-to-roll CLIP, or r2rCLIP. Prior to r2rCLIP, a batch of printed particles would need to be manually processed, a slow and labor-intensive process. The automation of r2rCLIP now enables unprecedented fabrication rates of up to 1 million particles per day.<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1710891940620-3d_printing_particles_setup-resized_0.png.png" style="width: 100%px;" class="fr-fic fr-dib">The r2rCLIP setup in the DeSimone lab runs from right to left. The printing occurs at the area below the red piece. | Image courtesy of DeSimone Research GroupIf this sounds like a familiar form for manufacturing, that’s intentional.“You don’t buy stuff you can’t make,” said DeSimone, who is also the Sanjiv Sam Gambhir Professor in Translational Medicine at Stanford Medicine. “The tools that most researchers use are tools for making prototypes and test beds, and to prove important points. My lab does translational manufacturing science – we develop tools that enable scale. This is one of the great examples of what that focus has meant for us.”There are tradeoffs in 3D printing of <a href="https://doi.org/10.1126/sciadv.abq2846" data-extlink="" target="_blank">resolution versus speed</a>. For instance, other 3D printing processes can print much smaller – on the nanometer scale – but are slower. And, of course, macroscopic 3D printing has already gained a foothold (literally) in mass manufacturing, in the form of shoes, household goods, machine parts, football helmets, dentures, hearing aids, and more. This work addresses opportunities in between those worlds.“We’re navigating a precise balance between speed and resolution,” said Kronenfeld. “Our approach is distinctively capable of producing high-resolution outputs while preserving the fabrication pace required to meet the particle production volumes that experts consider essential for various applications. Techniques with potential for translational impact must be feasibly adaptable from the research lab scale to that of industrial production.”<h2>Hard and soft</h2>The researchers hope that the r2rCLIP process sees wide adoption by other researchers and industry. Beyond that, DeSimone believes that 3D printing as a field is quickly evolving past questions about the process and toward ambitions about the possibilities.“r2rCLIP is a foundational technology,” said DeSimone. “But I do believe that we’re now entering a world focused on 3D products themselves more so than the process. These processes are becoming clearly valuable and useful. And now the question is: What are the high-value applications?”For their part, the researchers have already experimented with producing both hard and soft particles, made of ceramics and of hydrogels. The first could see applications in microelectronics manufacturing and the latter in drug delivery in the body.“There’s a wide array of applications, and we’re just beginning to explore them,” said Maria Dulay, senior research scientist in the DeSimone lab and co-author of the paper. “It’s quite extraordinary, where we’re at with this technique.”Additional co-authors are Lukas Rother, who was a visiting master’s student at the time of this work, and Max Saccone, a postdoctoral scholar in chemical engineering and radiology. DeSimone is also a professor, by courtesy, in chemistry in the&nbsp;<a href="https://humsci.stanford.edu/" data-extlink="" target="_blank">School of Humanities and Sciences</a>, materials science and engineering in the School of Engineering, and operations, information, and technology in the&nbsp;<a href="https://www.gsb.stanford.edu/" data-extlink="" target="_blank">Graduate School of Business</a>. He is a member of&nbsp;<a href="http://biox.stanford.edu/" data-extlink="" target="_blank">Stanford Bio-X</a>, the&nbsp;<a href="https://humanperformance.stanford.edu/" data-extlink="" target="_blank">Wu Tsai Human Performance Alliance</a>, and the&nbsp;<a href="http://cancer.stanford.edu/" data-extlink="" target="_blank">Stanford Cancer Institute</a>, and a faculty fellow of&nbsp;<a href="https://chemh.stanford.edu/" data-extlink="" target="_blank">Sarafan ChEM-H</a>, co-director of the&nbsp;<a href="https://canarycenter.stanford.edu/" data-extlink="" target="_blank">Canary Center at Stanford for Cancer Early Detection</a>, and founding faculty director of the Center for&nbsp;<a href="https://stemmteams.stanford.edu/" data-extlink="" target="_blank">STEMM&nbsp;Mentorship</a>&nbsp;at Stanford.

The 3D-printed DeSimone Lab logo, featuring a Buckyball geometry, demonstrates the r2rCLIP system’s ability to produce complex, non-moldable shapes with micron-scale features. | Image courtesy of DeSimone Research Group, SEM courtesy of Stanford Nano Shared Facilities

A new process for microscale 3D printing creates particles of nearly any shape for applications in medicine, manufacturing, research and more – at the pace of up to 1 million particles a day.

New high-speed microscale 3D printing technique

MIT researchers have used 3D printing to produce self-heating microfluidic devices, demonstrating a technique which could someday be used to rapidly create cheap, yet accurate, tools to detect a host of diseases.Microfluidics, miniaturized machines that manipulate fluids and facilitate chemical reactions, can be used to detect disease in tiny samples of blood or fluids. At-home test kits for Covid-19, for example, incorporate a simple type of microfluidic.But many microfluidic applications require chemical reactions that must be performed at specific temperatures. These more complex microfluidic devices, which are typically manufactured in a clean room, are outfitted with heating elements made from gold or platinum using a complicated and expensive fabrication process that is difficult to scale up.Instead, the MIT team used multimaterial 3D printing to create self-heating microfluidic devices with built-in heating elements, through a single, inexpensive manufacturing process. They generated devices that can heat fluid to a specific temperature as it flows through microscopic channels inside the tiny machine.Their technique is customizable, so an engineer could create a microfluidic that heats fluid to a certain temperature or given heating profile within a specific area of the device. The low-cost fabrication process requires about $2 of materials to generate a ready-to-use microfluidic.The process could be especially useful in creating self-heating microfluidics for remote regions of developing countries where clinicians may not have access to the expensive lab equipment required for many diagnostic procedures.“Clean rooms in particular, where you would usually make these devices, are incredibly expensive to build and to run. But we can make very capable self-heating microfluidic devices using additive manufacturing, and they can be made a lot faster and cheaper than with these traditional methods. This is really a way to democratize this technology,” says Luis Fernando Velásquez-García, a principal scientist in MIT’s Microsystems Technology Laboratories (MTL) and senior author of a paper describing the fabrication technique.He is joined on the paper by lead author Jorge Cañada Pérez-Sala, an electrical engineering and computer science graduate student. The research will be presented at the PowerMEMS Conference this month.<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1702991035117-MIT-Heated-Microfluidics-02-press.jpg" style="width: 766px;" class="fr-fic fr-dib">The self-heating microfluidic devices, such as the one shown, can be made rapidly and cheaply in large numbers, and could someday help clinicians in remote parts of the world detect diseases without the need for expensive lab equipment. Image: Courtesy of the researchers<h2>An insulator becomes conductive</h2>This new fabrication process utilizes a technique called multimaterial extrusion 3D printing, in which several materials can be squirted through the printer’s many nozzles to build a device layer by layer. The process is monolithic, which means the entire device can be produced in one step on the 3D printer, without the need for any post-assembly.To create self-heating microfluidics, the researchers used two materials — a biodegradable polymer known as polylactic acid (PLA) that is commonly used in 3D printing, and a modified version of PLA.The modified PLA has mixed copper nanoparticles into the polymer, which converts this insulating material into an electrical conductor, Velásquez-García explains. When electrical current is fed into a resistor composed of this copper-doped PLA, energy is dissipated as heat.“It is amazing when you think about it because the PLA material is a dielectric, but when you put in these nanoparticle impurities, it completely changes the physical properties. This is something we don’t fully understand yet, but it happens and it is repeatable,” he says.Using a multimaterial 3D printer, the researchers fabricate a heating resistor from the copper-doped PLA and then print the microfluidic device, with microscopic channels through which fluid can flow, directly on top in one printing step. Because the components are made from the same base material, they have similar printing temperatures and are compatible.Heat dissipated from the resistor will warm fluid flowing through the channels in the microfluidic.In addition to the resistor and microfluidic, they use the printer to add a thin, continuous layer of PLA that is sandwiched between them. It is especially challenging to manufacture this layer because it must be thin enough so heat can transfer from the resistor to the microfluidic, but not so thin that fluid could leak into the resistor.The resulting machine is about the size of a U.S. quarter and can be produced in a matter of minutes. Channels about 500 micrometers wide and 400 micrometers tall are threaded through the microfluidic to carry fluid and facilitate chemical reactions.Importantly, the PLA material is translucent, so fluid in the device remains visible. Many processes rely on visualization or the use of light to infer what is happening during chemical reactions, Velásquez-García explains.<h2>Customizable chemical reactors</h2>The researchers used this one-step manufacturing process to generate a prototype that could heat fluid by 4 degrees Celsius as it flowed between the input and the output. This customizable technique could enable them to make devices which would heat fluids in certain patterns or along specific gradients.“You can use these two materials to create chemical reactors that do exactly what you want. We can set up a particular heating profile while still having all the capabilities of the microfluidic,” he says.However, one limitation comes from the fact that PLA can only be heated to about 50 degrees Celsius before it starts to degrade. Many chemical reactions, such as those used for polymerase chain reaction (PCR) tests, require temperatures of 90 degrees or higher. And to precisely control the temperature of the device, researchers would need to integrate a third material that enables temperature sensing.In addition to tackling these limitations in future work, Velásquez-García wants to print magnets directly into the microfluidic device. These magnets could enable chemical reactions that require particles to be sorted or aligned.At the same time, he and his colleagues are exploring the use of other materials that could reach higher temperatures. They are also studying PLA to better understand why it becomes conductive when certain impurities are added to the polymer.“If we can understand the mechanism that is related to the electrical conductivity of PLA, that would greatly enhance the capability of these devices, but it is going to be a lot harder to solve than some other engineering problems,” he adds.“In Japanese culture, it’s often said that beauty lies in simplicity. This sentiment is echoed by the work of Cañada and Velasquez-Garcia. Their proposed monolithically 3D-printed microfluidic systems embody simplicity and beauty, offering a wide array of potential derivations and applications that we foresee in the future,” says Norihisa Miki, a professor of mechanical engineering at Keio University in Tokyo, who was not involved with this work.“Being able to directly print microfluidic chips with fluidic channels and electrical features at the same time opens up very exiting applications when processing biological samples, such as to amplify biomarkers or to actuate and mix liquids. Also, due to the fact that PLA degrades over time, one can even think of implantable applications where the chips dissolve and resorb over time,” adds Niclas Roxhed, an associate professor at Sweden’s KTH Royal Institute of Technology, who was not involved with this study.

MIT researchers developed a fabrication process to produce self-heating microfluidic devices in one step using a multi-material 3D printer. Pictured is an example of one of the devices. Image: Courtesy of the researchers

The one-step fabrication process rapidly produces miniature chemical reactors that could be used to detect diseases or analyze substances.

Scientists 3D print self-heating microfluidic devices

By Mikael Boedler, INKATRONIC GmbH | <a href="mailto:mb@inkatronic.com" target="_blank" id="isPasted">mb@inkatronic.com</a> Niederdorfstrasse 6, 4063 Hörsching Tel.: +43 7221 22298 In this article, we will discuss the different aspects of an effective ink delivery system. We will focus on a recirculating inkjet system as they are highly in demand in industry, especially where functional fluids come into play. Though recirculating printheads are mostly on the same price level as non-recirculating, gravity feed equivalents the ink supply system needed is much more intricate and as a result, significantly more challenging to implement (an example of a recirculating ink delivery system is shown in figure 1 below). The benefits of recirculating systems, however, are clearly outlined in the next section making it a worthy endeavour.<img src="https://images.wevolver.com/eyJidWNrZXQiOiJ3ZXZvbHZlci1wcm9qZWN0LWltYWdlcyIsImtleSI6ImZyb2FsYS8xNjk1MTE4MDUzNjg1LUZpZ3VyZS0xLnBuZyIsImVkaXRzIjp7InJlc2l6ZSI6eyJ3aWR0aCI6OTUwLCJmaXQiOiJjb3ZlciJ9fX0=" style="width: 373px;" class="fr-fic fr-dib">Figure 1 - INKATRONIC Scalable Circulating Ink Supply.<h3>Advantages of Recirculating Inkjet Technology in Industry</h3>Improved Print Quality - Recirculating printheads maintain a consistent ink temperature and viscosity, resulting in more consistent droplet formation when jetting at various frequencies. This leads to a better print quality with sharper details and better lay-down accuracy. Reduced Nozzle failures - Continuous ink circulation helps prevent nozzle failures caused by ingesting air, ink drying out, or ink settling, ensuring uninterrupted printing. Faster Start-Up Times - most recirculating printheads can start printing immediately, whereas gravity-fed printheads may require cleaning cycles to recover missing nozzles. Enhanced Printhead Longevity - The reduced risk of nozzle clogs and more stable operating conditions can extend the lifespan of recirculating printheads when compared to gravity feed systems. Improved Jetting Consistency - The stability in ink properties provided by recirculating printheads helps maintain consistent output across multiple print jobs, making them suitable for high-volume and continuous printing applications. Reduced Maintenance - Gravity feed printheads may require more frequent cleaning, purging, and maintenance, while recirculating printheads need less attention, leading to lower downtime and operating costs.<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1699455810628-B-and-B-2024%28e-mail%29.jpg" style="width: 766px;" class="fr-fic fr-dib">Join us in Berlin and/or Boston and lets us RESHAPE the Future of Electronics, making it Additive, Sustainable, Hybrid, Wearable, and 3D - techblick.comJoin us in Berlin and/or Boston and lets us RESHAPE the Future of Electronics, making it Additive, Sustainable, Hybrid, Wearable, and 3D - techblick.com<h3>Basic Principles of a Recirculating Ink Delivery System</h3>In theory, a recirculating ink supply is simple. By creating a pressure difference between the “in” and “out” ports of a printhead a flow of ink is generated (see Figure 2). At the same time, the correct pressure difference must be maintained to generate a slightly negative meniscus pressure at the nozzles. Achieving such a state initially is relatively easy, the hard part is maintaining it while the printhead starts jetting, recirculating pumps run and ink is refilled to compensate for the rate of ink leaving the system.<img src="https://images.wevolver.com/eyJidWNrZXQiOiJ3ZXZvbHZlci1wcm9qZWN0LWltYWdlcyIsImtleSI6ImZyb2FsYS8xNjk1MTE4MjAyMzMxLUZpZ3VyZS0yLnBuZyIsImVkaXRzIjp7InJlc2l6ZSI6eyJ3aWR0aCI6OTUwLCJmaXQiOiJjb3ZlciJ9fX0=" style="width: 300px;" class="fr-fic fr-dib">Figure 2 - A simple diagram showing two ink tanks with different pressures connected to a printhead. Pin is higher than Pout causing ink flow through the printhead. The overall pressure at the printhead will determine if a meniscus is held at the printhead nozzles.<img src="https://images.wevolver.com/eyJidWNrZXQiOiJ3ZXZvbHZlci1wcm9qZWN0LWltYWdlcyIsImtleSI6ImZyb2FsYS8xNjk1MTE4MjEwNjI0LUZpZ3VyZS0zLnBuZyIsImVkaXRzIjp7InJlc2l6ZSI6eyJ3aWR0aCI6OTUwLCJmaXQiOiJjb3ZlciJ9fX0=" style="width: 300px;" class="fr-fic fr-dib">Figure 3 - INKATRONIC Single Head Circulating Ink Supply.<h3>What are the Requirements for a Recirculating Ink Delivery System</h3> Pressure Control A meniscus pressure operating window is around ±2 mbar. Though changes within this range are unlikely to affect jetting stability, drop properties will always be affected by the smallest changes causing shifts in printed densities. For this reason, keeping the meniscus pressure within an optimal range is essential. Ink Pumps A reliable ink pump is essential for circulating ink through the system. Diaphragm pumps are commonly used for inkjet applications due to their accuracy and low maintenance requirements, though they must offer good speed control. Sharp start/stop operations are undesired and low pulsation is essential. Peristaltic pumps have their advantages but they need more frequent maintenance with their tubes, while gear pumps should be avoided due to their high shear rates which can affect an ink’s properties in circulating loops. For good chemical resistance, in the case of diaphragm pumps, they should contain FFKM valves and seals. Teflon is the recommended material for membranes.<img src="https://images.wevolver.com/eyJidWNrZXQiOiJ3ZXZvbHZlci1wcm9qZWN0LWltYWdlcyIsImtleSI6ImZyb2FsYS8xNjk1MTE4MjYzODEwLUlua2F0cm9uaWMtYm9vdGguanBnIiwiZWRpdHMiOnsicmVzaXplIjp7IndpZHRoIjo5NTAsImZpdCI6ImNvdmVyIn19fQ==" style="width: 530px;" class="fr-fic fr-dib">Join us at TechBlick's Future of Electronics RESHAPED conference &amp; tradeshow in Berlin on 17-18 OCT 2023 - <a target="_blank" rel="noopener noreferrer noopener noreferrer" data-fr-linked="true" href="//www.techblick.com/electronicsreshaped">www.techblick.com/electronicsreshaped</a>. For your special attendee discounts please contact us at <a href="mailto:mb@inkatronic.com" target="_blank" id="isPasted">mb@inkatronic.com</a>. Valves As a general rule, valves should be avoided where possible. If needed they have to be compact, with FFKM elastomers, large orifices, and low power consumption. This combination is often not available as standard and a partnership with a manufacturer is required to develop such valves. Pressure Spikes Pumps and valves create varying pulses of pressure, each of them, or in combination, can lead to undesired spikes in pressure. Pressure spikes can cause an immediate loss of nozzles. A positive spike can float a nozzle causing nozzle plate wetting (as shown in figure 3) and a cleaning stop. A negative pressure spike can lead to nozzle drop-outs by the ingestion of air (as shown in figure 4). In the case of a momentary ingestion of air, this is less consequential as the circulating flow of ink will quickly recover the nozzles. An acceptable range for pressure spikes can be +5 to -10 mbar, noting that the “in” pressure is most sensitive to this. It should also be noted that in some cases when large amounts of nozzles are started/stopped simultaneously they themselves can cause pressure spikes at the inlet side of the printhead. <img src="https://images.wevolver.com/eyJidWNrZXQiOiJ3ZXZvbHZlci1wcm9qZWN0LWltYWdlcyIsImtleSI6ImZyb2FsYS8xNjk1MTE4MzMzNzU5LUZpZ3VyZS00LnBuZyIsImVkaXRzIjp7InJlc2l6ZSI6eyJ3aWR0aCI6OTUwLCJmaXQiOiJjb3ZlciJ9fX0=" style="width: 490px;" class="fr-fic fr-dib">Figure 4 - Shows a printhead nozzle plate wetting. This is due to a positive pressure at the nozzle plate. <img src="https://images.wevolver.com/eyJidWNrZXQiOiJ3ZXZvbHZlci1wcm9qZWN0LWltYWdlcyIsImtleSI6ImZyb2FsYS8xNjk1MTE4MzQ0ODE5LUZpZ3VyZS01LnBuZyIsImVkaXRzIjp7InJlc2l6ZSI6eyJ3aWR0aCI6OTUwLCJmaXQiOiJjb3ZlciJ9fX0=" style="width: 516px;" class="fr-fic fr-dib">Figure 5 - Shows a printhead nozzle ingesting air. This is due to too high negative pressure at the nozzle plate.Tubing and Connectors Appropriate fittings and tubing should be used that are compatible with the inks chosen for the printing application. Long-term testing should be conducted to observe shrinking, swelling, and sweating. All tubes should be kept as short as possible and with multiple heads they have to be exactly equal in the length. High-quality connectors are recommended as a leaking inkjet system can cause lots of trouble to fix, not to mention the mess. More critical though, is the ingestion of air at any point of the negative pressure side of the system, such a leak is almost impossible to identify. This causes Ink foaming which provokes large jetting dropouts and the level control system to give false readings, which can cause an ink overflow. Materials for Manifolds and Tanks The material chosen for an ink tank should be compatible with the ink chemistry, preventing any chemical reactions or contamination. Common materials for ink tanks are stainless steel, high-density polyethylene (HDPE), polypropylene (PP) and aluminium. In the case of aluminium, it should never be used with water-based inks. Sedimentation and Draining of the system Sedimentation can occur in only a few hours which leads to unstable jetting and nozzle clogging. To avoid sedimentation of high-density inks they need constant motion or stirring. Ink should be kept circulating through the entire ink supply system and extended idle times should be avoided. For a weekend shutdown, it is recommended to implement an automatic draining process to remove the ink from the system and keep it agitated in the main ink reservoir. Temperature Control Ink temperature should be maintained precisely at the optimal value, deviating only ±1°C. This has to be controlled at the tanks and at each printhead. The tank heaters have to be well distributed, local overheating of ink must be avoided. Flow-through heaters in the ink recirculation lines can be used in addition, if needed. Experiments have to be conducted in order to determine an ink’s sensitivity to temperature. Printheads with integrated heaters should reach the target ink temperature with the heater switched off, otherwise the temperature reading by the head thermistor may not be representative of the ink temperature at the “in” and “out” ports. Printhead heaters should be used for fine-tuning the ink temperature, raising it by not more than 2°C. Degassing, Air Bubble Removal Ink formulations can contain dissolved gases or air bubbles, which can disrupt the flow of a fluid within the printhead. A degasser removes these entrapped gases from the ink, resulting in more stable and reliable jetting. This is especially recommended for water-based inks, while UV and solvent-based inks will always show improvements from this.<h3>The Parameters for Setting up an Inkjet System</h3>For each specific ink and printhead, a different set of parameters will need to be determined. These parameters include: - Temperature. - “In” and “out” pressures. - Flow rate. - Head voltage. - Waveform. These parameters must be determined experimentally by setting up an ink supply system, with a chosen printhead, the printhead electronics and the ink of choice. When testing a new ink the starting point should be to set the recommended temperature/viscosity set-points provided by the ink manufacturer in accordance with the printhead requirements. With the right temperature settings the “in” and “out” pressures are set in the range which prevents the printhead from dripping or sucking in air. The resulting flow rates are in a range of 10 to 200 ml/min depending on the printhead and have to be measured and maintained. At this point, the jetting performance can be analysed using a dropwatcher. The “in”/”out” pressures can now be adjusted with each jetting trial to find the region within which we achieve the best jetting performance. A flow rate that becomes too low can cause jetting instability and a delay/complete loss of nozzle recovery. A flow rate that is too high can affect the jetting straightness. The next parameter to test is the temperature. Temperature changes during the operation of a system should not fluctuate more than ±1°C. Any changes in temperature during jetting can affect drop size, jetting speed,as &nbsp;and jetting stability. As with pressure, temperature should be adjusted between jetting tests under the dropwatcher in increments of 0.5°C, while keeping other parameters constant. This should also produce a profile showing the ideal range in jetting performance, this time, relative to temperature. If the ideal temperature is different to the temperature set at the start of the procedure, the pressure range test can be repeated to see if the optimal pressure range changes with the new temperature value. Both pressure and temperature range tests would need to be repeated until the optimal pressure and temperature ranges stay constant. This entire procedure has to be repeated for each different ink chemistry, though it is a more complex procedure to swap out a printhead to test with the same ink. It is recommended to select as few printheads as early as possible in the development stages of a printing solution to avoid uneconomically lengthy development times. Functional fluids often have a high amount of solids in their chemistry and as such require frequent/constant agitation to prevent sedimentation, mentioned earlier. For chemists, it’s a challenge to design such fluids within the low viscosity requirements of piezo printheads, somewhere between 4 to 20 mPa s. Testing is recommended to avoid unpleasant surprises in the form of damaged printheads. Other parameters such as head voltage and waveform can also be analysed, however, they are outside of the scope of this article. A dedicated apparatus for complex inkjet development is the INKATRONIC Test Bench, with Dropwatcher shown in Figure, 6 below. With such equipment it is possible to gain productivity and have all the necessary tools at your side to effectively achieve your targets. <img src="https://images.wevolver.com/eyJidWNrZXQiOiJ3ZXZvbHZlci1wcm9qZWN0LWltYWdlcyIsImtleSI6ImZyb2FsYS8xNjk1MTE4NTQ2NzUwLUZpZ3VyZS02LmpwZyIsImVkaXRzIjp7InJlc2l6ZSI6eyJ3aWR0aCI6OTUwLCJmaXQiOiJjb3ZlciJ9fX0=" style="width: 716px;" class="fr-fic fr-dib">Figure 6 - Shows the INKATRONIC Test Bench which includes a Meteor dropwatcher for analysing ink jetting in microscopic detail as well as a vacuum table for test prints.<hr><h3>Join us at TechBlick's Future of Electronics RESHAPED conference &amp; tradeshow in Berlin on 17-18 OCT 2023 - <a href="https://www.techblick.com/electronicsreshaped." target="_blank" rel="noopener noreferrer">www.techblick.com/electronicsreshaped.</a> For your special attendee discounts please contact us at <a href="mailto:mb@inkatronic.com" target="_blank" id="isPasted">mb@inkatronic.com</a>.</h3><img src="https://images.wevolver.com/eyJidWNrZXQiOiJ3ZXZvbHZlci1wcm9qZWN0LWltYWdlcyIsImtleSI6ImZyb2FsYS8xNjk1MTE4NTg5OTQxLTIuQWdlbmRhLUV4aGliaXRpb24tTE9HT1MtKEJFUkxJTi0yMDIzKS1zbWFsbC5qcGciLCJlZGl0cyI6eyJyZXNpemUiOnsid2lkdGgiOjk1MCwiZml0IjoiY292ZXIifX19" style="width: 697px;" class="fr-fic fr-dib">

Ink Delivery System for Recirculating Piezo Printheads

In this article, we will discuss the different aspects of an effective ink delivery system. We will focus on a recirculating inkjet system as they are highly in demand in industry, especially where functional fluids come into play.

Functional Fluids: Designing an Ink Delivery System for Recirculating Piezo Printheads

However, in a recent <a data-hook="linkViewer" href="https://www.linkedin.com/company/71510477/admin/#" rel="noopener noreferrer" tabindex="0" target="_blank">TechBlick</a> talk, as shown in slide 1, &nbsp;Dr&nbsp;<a data-hook="linkViewer" href="https://www.linkedin.com/company/71510477/admin/#" rel="noopener noreferrer" tabindex="0" target="_blank">Aart-Jan Hoeven</a> showed an example in microfluidics where EHD could delvier value. Here, this technology could enable the electrode widths or pitches to be narrowed from 30-40um (possible with industrial inkjet) to perhaps 1-5um using EHD, thus saving space. This will support the miniaturization trend of microfluidics, making possible to even integrate them into the human body In slide 2&nbsp;<a data-hook="linkViewer" href="https://www.linkedin.com/company/71510477/admin/#" rel="noopener noreferrer" tabindex="0" target="_blank">DoMicro BV</a> &#39;s laboratory-scale nano printer can be seen in more detail. It is able to deposit ultrafine features digitally! This DM50-ENP printer is generating significant interest and was developed as part of E-Nanoprint-Pro project <a data-hook="linkViewer" href="https://www.linkedin.com/company/71510477/admin/#" rel="noopener noreferrer" tabindex="0" target="_blank">Marcel Grooten</a> <a data-hook="linkViewer" href="https://www.linkedin.com/company/71510477/admin/#" rel="noopener noreferrer" tabindex="0" target="_blank">Lars Wienholts</a>&nbsp;<div data-hook="rcv-block7" type="paragraph"> </div><a href="https://www.techblick.com/blog/hashtags/EHDjet" tabindex="0" target="_self">#EHDjet</a> <a href="https://www.techblick.com/blog/hashtags/microfluidics" tabindex="0" target="_self">#microfluidics</a> <a href="https://www.techblick.com/blog/hashtags/printedelectronics" tabindex="0" target="_self">#printedelectronics</a>&nbsp; <a href="https://www.techblick.com/post/microfluidics-and-electrohydrodynamic-printing-ehd" rel="noopener noreferrer" target="_blank" id="isPasted"></a><div data-hook="rcv-block8" type="paragraph">Read more at <a href="https://www.techblick.com/post/microfluidics-and-electrohydrodynamic-printing-ehd" id="isPasted" rel="noopener noreferrer" target="_blank">https://www.techblick.com/post/microfluidics-and-electrohydrodynamic-printing-ehd</a></div><div data-hook="rcv-block9" type="empty-line"> </div><div data-hook="galleryViewer"><div data-key="pro-gallery-inner-container" tabindex="-1"><div data-hook="item-link-wrapper" data-id="37406add-280f-4f68-a1bb-bd2dc022b75b_0" data-idx="0" tabindex="-1"><div data-hash="37406add-280f-4f68-a1bb-bd2dc022b75b_0" data-hook="item-container" data-id="37406add-280f-4f68-a1bb-bd2dc022b75b_0" data-idx="0" tabindex="0"><div data-hook="item-wrapper"><div data-hook="image-item"><img alt="" data-idx="0" src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1666115384724-1666115384724.png" class="fr-fic fr-dii"></div><div data-hook="item-hover-0"> </div></div></div></div><div data-hook="item-link-wrapper" data-id="9c1fb8d4-c648-4a48-9d8e-997f4a7c6018_1" data-idx="1" tabindex="-1"><div data-hash="9c1fb8d4-c648-4a48-9d8e-997f4a7c6018_1" data-hook="item-container" data-id="9c1fb8d4-c648-4a48-9d8e-997f4a7c6018_1" data-idx="1" tabindex="-1"><div data-hook="item-wrapper"><div data-hook="image-item"><img alt="" data-idx="1" src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1666115384815-1666115384815.png" class="fr-fic fr-dii"></div><div data-hook="item-hover-1"> </div></div></div></div><div data-hook="item-link-wrapper" data-id="18101a19-61c3-4dd6-8179-f94a7f25b37c_2" data-idx="2" tabindex="-1"><div data-hash="18101a19-61c3-4dd6-8179-f94a7f25b37c_2" data-hook="item-container" data-id="18101a19-61c3-4dd6-8179-f94a7f25b37c_2" data-idx="2" tabindex="-1"><div data-hook="item-wrapper"><div data-hook="image-item"><img alt="" data-idx="2" src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1666115384906-1666115384906.png" class="fr-fic fr-dii"></div></div></div></div></div></div>

 EHD is a promising digital printing technology for going beyond the resolution limits of inkjet. Most examples showcase electronic or display related applications. 



Microfluidics and Electrohydrodynamic printing (EHD)?

This article is a part of our <a href="http://www.wevolver.com/student-program" target="_blank">University Technology Exposure Program</a>. The program aims to recognize and reward innovation from engineering students and researchers across the globe.In this article, we present a summary of the&nbsp;5&nbsp;submissions we published in&nbsp;May 2022&nbsp;as a part of the event.<h2 dir="ltr">Submissions from May 2022</h2>#1. <a href="https://www.wevolver.com/article/how-3d-printing-technology-be-used-to-fabricate-low-cost-microfluids-on-mm-scale" target="_blank">How 3D-printing technology be used to fabricate low-cost microfluids on mm-scale?</a> By <a href="https://www.wevolver.com/profile/harry.felton" target="_blank">Harry Felton</a>The submission relates to innovation in microfluidics. It&rsquo;s a branch of technology that deals with the control and manipulation of fluid in the order of microLitres or nanoLitres with the help of thin channels. The author explains how additive manufacturing can make experimenting with microfluidics accessible for education and scientific research.&nbsp;To ensure that the proposed technique is fully democratized, an open-source Autodesk Fusion add-in has also been developed, allowing any user to design and export interconnecting microfluidic channel scaffolds for 3D printing. By making the technology more accessible, the approach inspires the next generation of research in microfluidics.Read the complete article by visiting <a href="https://www.wevolver.com/article/how-3d-printing-technology-be-used-to-fabricate-low-cost-microfluids-on-mm-scale" target="_blank">this link</a>.#2. <a href="https://www.wevolver.com/article/phormica-a-functional-and-cost-effective-system-for-stigmergic-coordination-in-swarm-robots" target="_blank">Phormica, a functional and cost-effective system for stigmergic coordination in swarm robots&nbsp;</a>by <a href="https://www.wevolver.com/profile/garzon.ramos.david" target="_blank">Garzon Ramos David</a>Swarm robots are a group of robots that operate in a distributed (but collective) way to accomplish a task they individually can not. Their operation is often reminiscent of how social insects like ants work. To coordinate among the other members of the same species, insects change their environment by leaving chemicals (known as pheromone) to pass on some message.The author of this article presents the concept of phormica, a system that enables swarm robots to leave artificial pheromones to achieve stigmergic coordination and perform significantly better than the swarms that rely on other collective behaviors to carry out their tasks.Find out more about the idea <a href="https://www.wevolver.com/article/phormica-a-functional-and-cost-effective-system-for-stigmergic-coordination-in-swarm-robots" target="_blank">here</a>.#3. <a href="https://www.wevolver.com/article/bio-inspired-tissue-transportation-system-an-alternative-to-aspiration-based-devices-in-mis" target="_blank">Bio-inspired tissue transportation system, an alternative to aspiration-based devices in MIS</a> by <a href="https://www.wevolver.com/profile/aimee.sakes" target="_blank">Aimee Sakes</a>Minimally invasive surgeries provide surgeons with a means to carry out the operation with small cuts. The key benefits of minimally invasive surgeries are: they cause less pain to the patient; patients can recover quicker, reducing the burden on the hospitals; they are also considered safer.The article presents a concept of a tissue transportation system inspired by the egg-laying needle, also known as the ovipositor, of some species of parasitic wasp. As the adoption of minimally invasive surgeries increases, the proposed prototype might fill the need for longer and thinner transportation instruments in the future.Continue reading by following <a href="https://www.wevolver.com/article/bio-inspired-tissue-transportation-system-an-alternative-to-aspiration-based-devices-in-mis" target="_blank">this link</a>.#4. <a href="https://www.wevolver.com/article/reducing-the-noise-emission-from-an-aircraft-engine-at-its-source/" target="_blank">Reducing the noise emission from an aircraft engine at its source</a> by <a href="https://www.wevolver.com/profile/christopher.teruna" target="_blank">Christopher Teruna</a>Even though modern aircraft have become much quieter than before, the number of flights have significantly increased over the last two decades. This has given rise to a widespread problem of airplane-induced noise pollution, which is most dominant in areas near airports.This article presents a detailed review of the sources of noise within the aircraft and proposes some solutions that can fix the problem. Christopher, the author of the article, writes about using porous material for building the tips of aircraft wings to bring down the overall sound power level. The idea seems promising, and hence, more investigations are required to identify the relationship between the physical aspects of a porous material and their impact on sound generation. Once the characteristics of the application are better understood, it would be possible to manufacture tailor-made porous parts for different aircraft components.For more details, check out the <a href="https://www.wevolver.com/article/reducing-the-noise-emission-from-an-aircraft-engine-at-its-source/" target="_blank">complete article</a>.#5. <a href="https://www.wevolver.com/article/project-march-improving-the-quality-of-life-for-people-with-spinal-cord-injuries/" target="_blank">Project MARCH: Improving the Quality of Life for People with Spinal Cord Injuries</a> by <a href="https://www.wevolver.com/profile/ianthe.rijpkema" target="_blank">Ianthe Rijpkema</a>Spinal cord injuries are considered very serious due to the presence of multiple nerves that carry messages between the brain and other parts of the body. Injuries to the spine can cause paralysis or loss of sensation below the site of injury. Suffering from a spinal cord injury significantly reduces the satisfaction with life.To help patients stand up on their feet again, Project MARCH aims to build an exoskeleton that can be used in day-to-day life. The use of an exoskeleton comes with medical benefits and increased user satisfaction. Each year, as a part of Project MARCH, students strive to solve new challenges and improve on the existing state of the technology. The team behind the project, has made the software open-source and is striving to make hardware open-source as well for the greater good.&nbsp;To read the article, visit <a href="https://www.wevolver.com/article/project-march-improving-the-quality-of-life-for-people-with-spinal-cord-injuries/" target="_blank">this link</a>.<h2 dir="ltr">About the University Technology Exposure Program 2022</h2>Wevolver, in partnership with <a href="https://mouser.com/" target="_blank">Mouser Electronics</a> and <a href="https://www.ansys.com/academic" target="_blank">Ansys</a>, is excited to announce the launch of the University Technology Exposure Program 2022. The program aims to recognize and reward innovation from engineering students and researchers across the globe. Learn more about the program <a href="http://www.wevolver.com/student-program" target="_blank">here</a>.<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1655204331399-1655204331399.png" class="fr-fic fr-dib">

With articles related to Microfluidics, Swarm Robotics, Biomedical Instruments, Aviation, and more, University Technology Exposure Program saw another fantastic month of project showcases by student researchers.

University Technology Exposure Program 2022: May Update

FullControl GCode Designer is new open-source and free software for the unconstrained design of additive manufacturing print paths and related aspects of the manufacturing plan.ChallengeThe conventional workflow for additive manufacturing is to develop a CAD model, convert it to triangulated STL surface geometry, slice that model into layers, identify the print path for each layer, and output a manufacturing file (GCode). Each stage introduces errors and limitations.SolutionIn contrast, FullControl GCode Designer (www.fullcontrolgcode.com) turns this whole process on its head. Rather than creating a CAD model and then determining how to move a print head around to simply fill the required 3D volume, FullControl GCode Designer allows the precise print path to be designed directly. This provides unparalleled design freedom and epitomizes the concept of Design for Additive Manufacturing. It allows the designer to think “What can I produce by moving a nozzle with a controlled extrusion rate?” which can allow dramatically different structures to those seen conventionally.<iframe src="https://www.youtube.com/embed/KlxuZ5JnA0k?&amp;wmode=opaque&amp;rel=0" frameborder="0" allowfullscreen="" class="fr-draggable" style="width: 789px; height: 441px;"></iframe>ResultsFullControl allows unlimited exploration of 3D space for printing and of the potential capabilities of 3D printers. It’s been used to print single extrusions 10x wider than the nozzle diameter and other extrusions 10x narrower than the nozzle diameter. That means a 100-fold difference in design resolution of fully dense extrusions is possible from a single system, which is entirely incomparable with conventional additive manufacturing print paths. It’s an example of how FullControl GCode Designer encourages innovative thinking beyond the general design rules, which are actually based on principles of printing with slicer software rather than the true capabilities of 3D printing hardware. Similarly, creating structures with innovative texture and porosity is possible when explicitly designing the 3D movement of the nozzle whilst extruding.<table style="width: 100%;"><tbody><tr><td style="width: 50.0000%;"><div class="fr-img-space-wrap"><img src="https://images.wevolver.com/eyJidWNrZXQiOiJ3ZXZvbHZlci1wcm9qZWN0LWltYWdlcyIsImtleSI6ImZyb2FsYS8xNjIwOTgyNjAwOTc0LVN0cmluZyBleGFtcGxlLnBuZyIsImVkaXRzIjp7InJlc2l6ZSI6eyJ3aWR0aCI6OTUwLCJmaXQiOiJjb3ZlciJ9fX0=" style="width: 300px;" class="fr-fic fr-dib">String Example 10x Narrower&nbsp;</div></td><td style="width: 50.0000%;"><div class="fr-img-space-wrap"><img src="https://images.wevolver.com/eyJidWNrZXQiOiJ3ZXZvbHZlci1wcm9qZWN0LWltYWdlcyIsImtleSI6ImZyb2FsYS8xNjIwOTgyNjIzOTA0LTEweCB3aWR0aCBleGFtcGxlLmpwZyIsImVkaXRzIjp7InJlc2l6ZSI6eyJ3aWR0aCI6OTUwLCJmaXQiOiJjb3ZlciJ9fX0=" style="width: 300px;" class="fr-fic fr-dib" alt="10x Width Example String Structure">10x Width Example String Structure&nbsp;</div></td></tr><tr><td style="width: 50.0000%;"><img src="https://images.wevolver.com/eyJidWNrZXQiOiJ3ZXZvbHZlci1wcm9qZWN0LWltYWdlcyIsImtleSI6ImZyb2FsYS8xNjIwOTgyODE3MjQzLVJhbWVuIGV4YW1wbGUuanBnIiwiZWRpdHMiOnsicmVzaXplIjp7IndpZHRoIjo5NTAsImZpdCI6ImNvdmVyIn19fQ==" style="width: 300px;" class="fr-fic fr-dib">Noodle-Like Structure Example </td><td style="width: 50.0000%;"> <div class="fr-img-space-wrap"><img src="https://images.wevolver.com/eyJidWNrZXQiOiJ3ZXZvbHZlci1wcm9qZWN0LWltYWdlcyIsImtleSI6ImZyb2FsYS8xNjIwOTgyOTQwNTg1LVJpcHBsZSB0ZXh0dXJlIGV4YW1wbGUuanBnIiwiZWRpdHMiOnsicmVzaXplIjp7IndpZHRoIjo5NTAsImZpdCI6ImNvdmVyIn19fQ==" style="width: 300px;" class="fr-fic fr-dib">Ripple-Like Texture&nbsp;</div></td></tr></tbody></table><iframe src="https://www.youtube.com/embed/Sj3Nqtjfw0Q?&amp;wmode=opaque&amp;rel=0" frameborder="0" allowfullscreen="" class="fr-draggable" style="width: 789px; height: 598px;"></iframe>FullControl GCode Designer is applicable for a wide range of designs and applications. It’s been used to print highly controlled simple structures for material characterization as well as complex mathematical forms, in-situ process monitoring, hybrid manufacturing, and production runs &gt;1000. The benefits apply to structures designed and printed at the microscale, such as medical stents, to those at the other end of the spectrum such as large-format polymer and concrete 3D printing. Materials printed with FullControl include thermopolymers, ceramics, silicone, conductive metal inks, biological cell-laden hydrogels, fibre-reinforce polymers and many more materials. Wherever a print path is used, FullControl GCode Designer is relevant because the benefits translate across material systems and size scales. <div class="fr-img-space-wrap"><img src="https://images.wevolver.com/eyJidWNrZXQiOiJ3ZXZvbHZlci1wcm9qZWN0LWltYWdlcyIsImtleSI6ImZyb2FsYS8xNjIwOTgyOTkxNjEwLVN0ZW50IGV4YW1wbGUuanBnIiwiZWRpdHMiOnsicmVzaXplIjp7IndpZHRoIjo5NTAsImZpdCI6ImNvdmVyIn19fQ==" style="width: 300px;" class="fr-fic fr-dib">Stent Example<iframe src="https://www.youtube.com/embed/lWHxT3HQ4Wo?&amp;wmode=opaque&amp;rel=0" frameborder="0" allowfullscreen="" class="fr-draggable" style="width: 789px; height: 465px;"></iframe>&nbsp;</div>Major Benefits of the FullControl GCode Designer are<table border="1" cellpadding="0" cellspacing="0" width="584"></table><ul><li>Quality - the ability to optimize all aspects of the printing procedure to maximize quality, reliability and speed, and overcome any challenges associated with a specific material, printing system or part design.</li><li>Design file&nbsp;efficiency - the design file for the sinusoidal shoe sole concept in the image below requires about 1KB of data, whilst also allowing full parametric adjustment of the size and shape, whereas an STL file (nonparametric) of a similar model may require 1000000 times more data.</li><li>3D print paths and previously impossible structures – the stent in the image above was printed with continuous vertical extrusion (see the video below)</li><li>Hybrid manufacturing and multi-tool processes – FullControl facilitates the use of multiple tools and auxiliary equipment. Explicit design of tool movement paths eliminates the challenges of tool-part collisions during hybrid manufacturing and allows advanced manufacturing activities such as in-situ process monitoring.</li><li>The software is entirely free and requires no installation. It’s integrated into Excel, which is used as an extremely powerful user interface (enabling Excel’s broad functions to be used in design parameters). No CAD software or software licences are required.</li></ul> <div class="fr-img-space-wrap"><img src="https://images.wevolver.com/eyJidWNrZXQiOiJ3ZXZvbHZlci1wcm9qZWN0LWltYWdlcyIsImtleSI6ImZyb2FsYS8xNjIwOTgzMDUxNTQ5LVNob2Vzb2xlLmpwZyIsImVkaXRzIjp7InJlc2l6ZSI6eyJ3aWR0aCI6OTUwLCJmaXQiOiJjb3ZlciJ9fX0=" style="width: 300px;" class="fr-fic fr-dib">Sinusoidal Shoe Sole Example&nbsp;</div><iframe src="https://www.youtube.com/embed/e68Vc69yAo8?&amp;wmode=opaque&amp;rel=0" frameborder="0" allowfullscreen="" class="fr-draggable" style="width: 789px; height: 469px;"></iframe> For a detailed demonstration of the design workflow, see the technical introduction video (20 mins)&nbsp;<iframe src="https://www.youtube.com/embed/yGtyw3oLOVQ?&amp;wmode=opaque&amp;rel=0" frameborder="0" allowfullscreen="" class="fr-draggable" style="width: 791px; height: 437px;"></iframe>More information and other tutorials are available at <a href="//www.fullcontrolgcode.com" rel="noopener noreferrer" target="_blank">www.fullcontrolgcode.com</a><hr>CREATE Education would like to thank Andrew Gleadall for taking the time to share his work in research focusing on biomedical polymers and additive manufacturing at Loughborough University.To learn more about additive manufacturing solutions and how CREATE Education can help and support your University research visit <a href="https://www.createeducation.com/" rel="noopener noreferrer" target="_blank">www.createeeducation.com</a> or speak to our specialists at <a href="mailto:enquries@createeducation.com" rel="noopener noreferrer noopener noreferrer" target="_blank">enquries@createeducation.com</a>.

Ripple texture printed using the a simple print-path design, using a parametric FullControl design file.

Andy Gleadall, Lecturer at Loughborough University develops FullControl GCode Designer in the hope to empower people to do the impossible with scripts and slicers.

Open-Source Software for Unconstrained Design in Additive Manufacturing

Julio Aleman, a Bioengineering PhD student at the University of Pittsburgh Swanson School of Engineering is performing research in microphysiological systems.Like many researchers, Aleman needed a microwell array system with individual wells that have a specific size, shape and density. In fact, Aleman needed two different microwell arrays that would support the injection moulding of hydrogels and serve as “master moulds” – the original moulds that he could replicate. In turn, these replicate moulds would be used for microwell fabrication. <img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1605869692139-PittsburghCaseStudy2.png">Hydrogel mould of 484-microwell arrayTo produce master moulds like this, photolithography (optical lithography or UV lithography) is often used. The process begins by spin coating a negative photoresist on a wafer to establish mould thickness and microwell depth. Photopatterning is achieved by light exposure through specialised high-resolution masks and finalised by chemical development of the master mould. Then, replicas of the master mould are made by casting pre-polymers over the negative template and polymerising them by thermal curing.Polydimethylsiloxane (PDMS) silicone is the biocompatible polymer that is most often used. Typically, the production of master moulds and masks requires specialised facilities and equipment. Micro-injection moulding can also produce master moulds, but the tooling is expensive and time-consuming to produce. <h1>An Alternative to Clean Room Photolithographic and Injection Moulding</h1>Projection Micro Stereolithography (PμSL) from Boston Micro Fabrication (BMF) allows for the rapid photo-polymerisation of a layer of resin with a flash of ultraviolet (UV) light at micro-scale resolution. PμSL offers an alternative to photosoft lithography, etching, deposition, micro-injection moulding, and other traditional microfabrication methods.PμSL, a form of micro 3D printing, can produce small components with fine features and tight tolerances that are otherwise impossible to create. PμSL is capable of achieving a resolution of 2µm~50µm and a tolerance of +/- 5µm~25µm, thus providing ultra-high-resolution that is mould-free and mask-free for fast prototyping and end-use parts.  <h1>Project Requirements for Two Master Moulds</h1>The University of Pittsburgh project needed master moulds for replicate silicone moulds that, in turn, would be used to make biomaterial-based microwells. Normally, master moulds require a cleanroom and can be challenging to characterise. Researchers can’t perform profilometer measurements until the moulds are baked, and a mould with the wrong dimensions means lost time and money.Julio Aleman’s project required fast turnaround times and high-volume production. Accuracy, resolution, and precision were critically important. Several PDMS replicas that were cured at 80° Celsius were needed and the repeated processes on the master mould had to have little to no impact on the dimensions while the master mould was also securely fixed in a substrate. Aleman knew that he would need moulds in two different sizes, and that the silicone moulds should allow for the bottoms of the hydrogel micro-wells to have constant and defined amounts of biomaterial once injected and polymerized onto a glass slide. After some preliminary discussions, he ordered parts from BMF.The master moulds that the University of Pittsburgh asked BMF to produce were square with a defined hole–pattern. The first mould was for a 64-microwell array. It had an overall area of 20 mm x 20 mm and a thickness of 1.65 mm. The diameter for each hole and the distance between holes was 600 microns, or 0.6 mm, and the base of each of the microwells had a height of 50 microns from the surface. The second mould was for a 484-microwell array. The overall area was the same as for the first mould (20 mm x 20 mm), but the thickness for the second mould was significantly less at 1 mm. There were also more holes – and the holes were smaller. These wells measured just 150 microns, or 0.15 mm, in diameter with a similar base height of 50 microns.3D printed mould for 64-microwell array<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1605869775020-PittsburghCaseStudy3.png">3D printed mould for 64-microwell array<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1605869800497-PittsburghCaseStudy4.png">3D printed mould for 484-microwell array<h1>Expert Advice and Flexible Material Selection</h1>BMF’s application team reviewed the designs for the University of Pittsburgh moulds. They recommended increasing the thickness of the second mould to greater than 1 mm. Otherwise, a mould that is too thin may experience part distortion or internal stresses during the printing process. Aleman revised the thickness and BMF then created sample parts using GR resin, a high-performance engineering material that is black in colour, able to withstand temperatures up to 102°C, and that supports sterilising.Because the COVID-19 pandemic limited Aleman’s access to university facilities, the graduate researcher limited his mould evaluation to microscopy. In turn, this meant that parts made of a dark resin would be more difficult to inspect. To support microscopic techniques, Aleman needed a resin that would allow more light to pass through so that the features of the resin mould could be more clearly seen. The solution was to use an HLT resin instead. This yellow resin from BMF offers greater transparency but still provides good impact strength, heat resistance, and support for autoclave sterilisation.<h1> </h1><h1>Speed, Accuracy and More</h1>&nbsp;Julio Aleman was pleased with the quick lead time – the moulds were delivered in just two weeks. Instead of waiting months to get a single injection-mould, he could provide a master mould to each member of the research team. The moulds also exhibited dimensional stability and, unlike spin coating in photolithography, did not require multiple fabrication steps. After hard baking some master moulds in an oven overnight, Aleman attached them to a surface with double-sided electrical tape. The moulds experienced only a 10 to 20-micrometre reduction in size, and that may have been caused by pressing the moulds against the surface or the tape while the moulds were still malleable from baking.Aleman also reported that after approximately 10 cycles of PDMS moulding, the BMF master moulds did not exhibit any bending or deformation. To prevent sticking, the replicate moulds were salinated with Vapor Phase Deposition (VPD). This treatment, which is also used with the SU8 moulds in photolithography, permitted the easy detachment of the PDMS moulds from the BMF master moulds. Aleman reported that the master mould with the larger features was easily salinated over one hour of exposure while the mould with smaller features required five hours or overnight exposure.<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1605869860170-PittsburghCaseStudy5.png">PDMS replica of 64-microwell array<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1605869888883-PittsburghCaseStudy6.png">PDMS replica of 484-microwell array<h1> </h1><h1>Proof-of-Concept for Your Next Project&nbsp;</h1>As the University of Pittsburgh project demonstrates, researchers can use micro 3D printing to speed microwell array fabrication. If your application requires proof-of-concept parts such as master moulds, BMF can harness the power of PμSL technology on your behalf. We can also help you with material selection and recommend the best microArch printer from our growing family of ultra-high resolution 3D printers.In an exclusive partnership with BMF, CREATE Education are sharing their knowledge, support and experience, to bring micro 3D printing technology to the forefront of their education community in the UK and Ireland, enabling breakthrough research and development.CREATE Education are committed to supporting educators, educational institutions, outreach and community programs with the aim to bring cutting edge technologies throughout the world, such as 3D printers, into education.To learn more about PμSL technology and micro 3D Printing for research, please contact <a href="https://bit.ly/ContactCREATEEd" rel="noopener noreferrer" target="_blank">CREATE Education’s specialists</a>.

Julio Aleman, a Bioengineering PhD student needed two different microwell array system with individual wells that would support injection moulding of hydrogels and serve as “master moulds”

University of Pittsburgh Speeds Microwell Fabrication with Micro 3D Printing

<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1570180135315-cell-quality-control-010.jpg" style="width: 667px;" class="fr-fic fr-dib">Georgia Tech graduate research assistant Mason Chilmonczyk examines a device after a plasma etch step in a reactive ion etching tool. The work was being done in the Institute of Electronics and Nanotechnology&rsquo;s Marcus Building clean room. (Credit: Rob Felt, Georgia Tech)&nbsp;Researchers have demonstrated an integrated technique for monitoring specific biomolecules &ndash; such as growth factors &ndash; that could indicate the health of living cell cultures produced for the burgeoning field of cell-based therapeutics.&nbsp;Using microfluidic technology to advance the preparation of samples from the chemically complex bioreactor environment, the researchers have harnessed electrospray ionization mass spectrometry (ESI-MS) to provide online monitoring that they believe will provide for therapeutic cell production the kind of precision quality control that has revolutionized other manufacturing processes.&nbsp;&ldquo;The way that the production of cell therapeutics is done today is very much an art,&rdquo; said&nbsp;<a href="http://www.me.gatech.edu/faculty/fedorov" target="_blank">Andrei Fedorov</a>, Woodruff Professor in the&nbsp;<a href="http://www.me.gatech.edu/" target="_blank">George W. Woodruff School of Mechanical Engineering</a> at the Georgia Institute of Technology. &ldquo;Process control must evolve very quickly to support the therapeutic applications that are emerging from bench science today. We think this technology will help us reach the goal of making these exciting cell-based therapies widely available.&rdquo;By measuring very low concentrations of specific compounds secreted or excreted by cells, the technique could also help identify which biomolecules &ndash; of widely varying sizes &ndash; should be monitored to guide the control of cell health. Ultimately, the researchers hope to integrate their label-free monitoring directly into high-volume bioreactors that will produce cells in quantities large enough to make the new therapies available at a reasonable cost and consistent quality.Development of the Dynamic Mass Spectrometry Probe (DMSP) was supported by the National Science Foundation (NSF) Engineering Research Center for Cell Manufacturing Technologies (CMaT), which is headquartered at Georgia Tech. The work was reported September 10 in the journal Biotechnology and Bioengineering.<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1570180203826-cell-quality-control-007.jpg" style="width: 676px;" class="fr-fic fr-dib">Georgia Tech graduate research assistant Mason Chilmonczyk prepares to fabricate a Dynamic Mass Spectrometry Probe in the Institute of Electronics and Nanotechnology&rsquo;s Marcus Building clean room. (Credit: Rob Felt, Georgia Tech) Traditional ESI-MS techniques have revolutionized analytical chemistry by allowing precise identification of complex biological compounds. Because of complex sample preparation requirements, existing approaches to ESI-MS require too much time to be useful for continuous monitoring of cell growth in bioreactors, where maintaining narrow parameters for specific indicators of cellular health is critical. Biological samples also contain salts, which must be removed before introduction into the ESI-MS system.To accelerate the analytical process, Fedorov and a team that included graduate research assistant Mason Chilmonczyk and research engineer Peter Kottke used microfluidic technology to help separate compounds of interest from the salts. Salt removal uses a monolithic device in which a size-selective membrane with nanoscale pores is placed between two fluid flows, one the chemically complex sample drawn from the bioreactors and the other salt-free water with conditioning compounds.&nbsp;The smaller salt molecules readily diffuse out of the sampled bioreactor flow through the nanopores, while the larger biomolecules mostly remain for the subsequent ESI-MS analysis. Meanwhile, chemical additives are at the same time introduced into the sample mixture through the same membrane nanopores to enhance ionization of the target biomolecules in the sampled mixture for improved ESI-MS analysis.&ldquo;We have used advanced microfabrication techniques to create a microfluidic device that will be able to treat samples in less than a minute,&rdquo; said Chilmonczyk. &ldquo;Traditional sample preparation can require hours to days.&rdquo;The process can currently remove as much as 99 percent of the salt, while retaining 80 percent of the biomolecules. Introduction of the conditioning chemicals allows the molecules to accept a greater charge, improving the capability of the mass spectrometer to detect low concentration biomolecules, and to measure large molecules.&ldquo;We can detect really high molecular weight molecules that the mass spectrometer normally wouldn&rsquo;t be able to detect,&rdquo; Fedorov said. &ldquo;The size difference in the molecules of interest can be dramatic, so the improvement in the limit of detection across a broad range of analyte molecular weights will allow this technique to be more useful in cell manufacturing.&rdquo;Because they use state of the art microfabrication techniques, the DMSP devices can be mass produced, allowing sampling to be scaled up to include multiple bioreactors at low cost. The small size of the device channels &ndash; which are just five microns tall &ndash; allows the system to produce results with samples as small as 20 nanoliters &ndash; with the potential for reducing that to as little as a single nanoliter.&ldquo;We need to monitor small concentrations of large biomolecules in this messy environment in a production line in such a way that we can check at any point how the cells are doing,&rdquo; Fedorov said. &ldquo;This system could continuously monitor whether certain molecules are excreted or secreted at a reduced or increased rate. By correlating these measurements with cell health and potency, we could improve the manufacturing process.&rdquo;Before the analytical techniques can be applied to quality control, the researchers must first identify biomolecules that indicate health of the growing cells. By sampling the bioreactor content locally in the immediate vicinity of cells and allowing identification of very small quantities of biochemicals, the DMSP technology can help researchers identify changes in molecular concentrations &ndash; which range from pico-molar to micro-molar &ndash; that may indicate the state of cells in the bioreactors. This would prompt adjustment of conditions in a bioreactor just in time to return to the state of healthy cell growth.&ldquo;In this situation, we often can&rsquo;t see the trees for the forest,&rdquo; said Fedorov. &ldquo;There is a lot of material available, but we are looking for just a handful of individual trees that indicate the health of the cells. Because the forest is overgrown, the few selected trees we need to examine are hard to find. This is a grand challenge technologically.&rdquo;

Close-up image shows the Dynamic Mass Spectrometry Probe developed to monitor the health of living cell cultures. (Credit: Rob Felt, Georgia Tech)

Researchers have demonstrated an integrated technique for monitoring specific biomolecules – such as growth factors – that could indicate the health of living cell cultures produced for the burgeoning field of cell-based therapeutics.