Tag Archives: microfluidic devices

A bioengineered robot hand with its own nervous system: machine/flesh and a job opening

A November 14, 2017 news item on phys.org announces a grant for a research project which will see engineered robot hands combined with regenerative medicine to imbue neuroprosthetic hands with the sense of touch,

The sense of touch is often taken for granted. For someone without a limb or hand, losing that sense of touch can be devastating. While highly sophisticated prostheses with complex moving fingers and joints are available to mimic almost every hand motion, they remain frustratingly difficult and unnatural for the user. This is largely because they lack the tactile experience that guides every movement. This void in sensation results in limited use or abandonment of these very expensive artificial devices. So why not make a prosthesis that can actually “feel” its environment?

That is exactly what an interdisciplinary team of scientists from Florida Atlantic University and the University of Utah School of Medicine aims to do. They are developing a first-of-its-kind bioengineered robotic hand that will grow and adapt to its environment. This “living” robot will have its own peripheral nervous system directly linking robotic sensors and actuators. FAU’s College of Engineering and Computer Science is leading the multidisciplinary team that has received a four-year, $1.3 million grant from the National Institute of Biomedical Imaging and Bioengineering of the [US] National Institutes of Health for a project titled “Virtual Neuroprosthesis: Restoring Autonomy to People Suffering from Neurotrauma.”

A November14, 2017 Florida Atlantic University (FAU) news release by Gisele Galoustian, which originated the news item, goes into more detail,

With expertise in robotics, bioengineering, behavioral science, nerve regeneration, electrophysiology, microfluidic devices, and orthopedic surgery, the research team is creating a living pathway from the robot’s touch sensation to the user’s brain to help amputees control the robotic hand. A neuroprosthesis platform will enable them to explore how neurons and behavior can work together to regenerate the sensation of touch in an artificial limb.

At the core of this project is a cutting-edge robotic hand and arm developed in the BioRobotics Laboratory in FAU’s College of Engineering and Computer Science. Just like human fingertips, the robotic hand is equipped with numerous sensory receptors that respond to changes in the environment. Controlled by a human, it can sense pressure changes, interpret the information it is receiving and interact with various objects. It adjusts its grip based on an object’s weight or fragility. But the real challenge is figuring out how to send that information back to the brain using living residual neural pathways to replace those that have been damaged or destroyed by trauma.

“When the peripheral nerve is cut or damaged, it uses the rich electrical activity that tactile receptors create to restore itself. We want to examine how the fingertip sensors can help damaged or severed nerves regenerate,” said Erik Engeberg, Ph.D., principal investigator, an associate professor in FAU’s Department of Ocean and Mechanical Engineering, and director of FAU’s BioRobotics Laboratory. “To accomplish this, we are going to directly connect these living nerves in vitro and then electrically stimulate them on a daily basis with sensors from the robotic hand to see how the nerves grow and regenerate while the hand is operated by limb-absent people.”

For the study, the neurons will not be kept in conventional petri dishes. Instead, they will be placed in  biocompatible microfluidic chambers that provide a nurturing environment mimicking the basic function of living cells. Sarah E. Du, Ph.D., co-principal investigator, an assistant professor in FAU’s Department of Ocean and Mechanical Engineering, and an expert in the emerging field of microfluidics, has developed these tiny customized artificial chambers with embedded micro-electrodes. The research team will be able to stimulate the neurons with electrical impulses from the robot’s hand to help regrowth after injury. They will morphologically and electrically measure in real-time how much neural tissue has been restored.

Jianning Wei, Ph.D., co-principal investigator, an associate professor of biomedical science in FAU’s Charles E. Schmidt College of Medicine, and an expert in neural damage and regeneration, will prepare the neurons in vitro, observe them grow and see how they fare and regenerate in the aftermath of injury. This “virtual” method will give the research team multiple opportunities to test and retest the nerves without any harm to subjects.

Using an electroencephalogram (EEG) to detect electrical activity in the brain, Emmanuelle Tognoli, Ph.D., co-principal investigator, associate research professor in FAU’s Center for Complex Systems and Brain Sciences in the Charles E. Schmidt College of Science, and an expert in electrophysiology and neural, behavioral, and cognitive sciences, will examine how the tactile information from the robotic sensors is passed onto the brain to distinguish scenarios with successful or unsuccessful functional restoration of the sense of touch. Her objective: to understand how behavior helps nerve regeneration and how this nerve regeneration helps the behavior.

Once the nerve impulses from the robot’s tactile sensors have gone through the microfluidic chamber, they are sent back to the human user manipulating the robotic hand. This is done with a special device that converts the signals coming from the microfluidic chambers into a controllable pressure at a cuff placed on the remaining portion of the amputated person’s arm. Users will know if they are squeezing the object too hard or if they are losing their grip.

Engeberg also is working with Douglas T. Hutchinson, M.D., co-principal investigator and a professor in the Department of Orthopedics at the University of Utah School of Medicine, who specializes in hand and orthopedic surgery. They are developing a set of tasks and behavioral neural indicators of performance that will ultimately reveal how to promote a healthy sensation of touch in amputees and limb-absent people using robotic devices. The research team also is seeking a post-doctoral researcher with multi-disciplinary experience to work on this breakthrough project.

Here’s more about the job opportunity from the FAU BioRobotics Laboratory job posting, (I checked on January 30, 2018 and it seems applications are still being accepted.)

Post-doctoral Opportunity

Dated Posted: Oct. 13, 2017

The BioRobotics Lab at Florida Atlantic University (FAU) invites applications for a NIH NIBIB-funded Postdoctoral position to develop a Virtual Neuroprosthesis aimed at providing a sense of touch in amputees and limb-absent people.

Candidates should have a Ph.D. in one of the following degrees: mechanical engineering, electrical engineering, biomedical engineering, bioengineering or related, with interest and/or experience in transdisciplinary work at the intersection of robotic hands, biology, and biomedical systems. Prior experience in the neural field will be considered an advantage, though not a necessity. Underrepresented minorities and women are warmly encouraged to apply.

The postdoctoral researcher will be co-advised across the department of Mechanical Engineering and the Center for Complex Systems & Brain Sciences through an interdisciplinary team whose expertise spans Robotics, Microfluidics, Behavioral and Clinical Neuroscience and Orthopedic Surgery.

The position will be for one year with a possibility of extension based on performance. Salary will be commensurate with experience and qualifications. Review of applications will begin immediately and continue until the position is filled.

The application should include:

  1. a cover letter with research interests and experiences,
  2. a CV, and
  3. names and contact information for three professional references.

Qualified candidates can contact Erik Engeberg, Ph.D., Associate Professor, in the FAU Department of Ocean and Mechanical Engineering at eengeberg@fau.edu. Please reference AcademicKeys.com in your cover letter when applying for or inquiring about this job announcement.

You can find the apply button on this page. Good luck!

Monitoring the life of bacteria in microdroplets

Trying to establish better ways to test the effect of drugs on bacteria has led the Institute of Physical Chemistry of the Polish Academy of Sciences to develop a new monitoring technique. From a Jan.  11, 2017 news item on Nanowerk,

So far, however, there has been no quick or accurate method of assessing the oxygen conditions in individual microdroplets. This key obstacle has been overcome at the Institute of Physical Chemistry of the Polish Academy of Sciences.

Not in rows of large industrial tanks, nor on shelves laden with test tubes and beakers. The future of chemistry and biology is barely visible to the eye: it’s hundreds and thousands of microdroplets, whizzing through thin tubules of microfluidic devices. The race is on to find technologies that will make it possible to carry out controlled chemical and biological experiments in microdroplets. At the Institute of Physical Chemistry of the Polish Academy of Sciences (IPC PAS) in Warsaw a method of remote, yet rapid and accurate assessment of oxygen consumption by micro-organisms living in individual microdroplets has been demonstrated for the first time.

“Devices for the cultivation of bacteria in microdroplets have the chance to revolutionize work on the development of new antibiotics and the study of mechanisms responsible for the acquisition of drug resistance by bacteria. In one small microfluidic system it is possible to accommodate several hundred or even several thousand microdroplets – and to carry out a different experiment in each of them, for example with different types of microorganisms and at different concentrations of antibiotic in each drop,” describes Prof. Piotr Garstecki (IPC PAS), then explains: “For such studies to be possible, one has to provide the bacteria with conditions for development for even a few weeks. Thus, knowledge about the flow of oxygen to the droplets and the rate of its consumption by the microorganisms becomes extremely important. In our latest system we demonstrate how to read this key information.”

A Jan. 11, 2017 IPC PAS press release on EurekAlert, which originated the  news item, describes the work in more detail,

The bioreactors of the future are water droplets with culture medium suspended in a carrier liquid with which they are immiscible (usually this is oil). In the channel of the microfluidic device each droplet is longer than it is wide and it almost completely fills its lumen; sizes matched in this manner ensure that the drops do not swop places in the channel and throughout the duration of the experiment they can be identified without any problems. At the same time, there has to be a thin layer of oil maintained continuously between each microdroplet and the wall of the channel. Without this, the bacteria would be in direct contact with the walls of the channel so they would be able to settle on them and move from drop to drop. Unfortunately, when the microdroplet is stationary, with time it pushes out the oil separating it from the walls, laying it open to contamination. For this reason the drops must be kept in constant motion – even for weeks.

Growing bacteria need culture medium, and waste products need to be removed from their environment at an appropriate rate. Information about the bacterial oxygen consumption in individual droplets is therefore crucial to the operation of microbioreactors.

“It is immediately obvious where the problem lies. In each of the hundreds of moving droplets measurements need to be carried out at a frequency corresponding to the frequency of division of the bacteria or more, in practice at least once every 15 minutes. In addition, the measurement cannot cause any interference in the microdroplets,” says PhD student Michal Horka (IPC PAS), a co-author of the publication in the journal Analytical Chemistry.

Help was at hand for the Warsaw researchers from chemists from the Austrian Institute of Analytical Chemistry and Food Chemistry at the Graz University of Technology. They provided polymer nanoparticles with a phosphorescent dye, which after excitation emit light for longer the higher the concentration of oxygen in the surrounding solution (the nanoparticles underwent tests at the IPC PAS on bacteria in order to determine their possible toxicity – none was found).

Research on monitoring oxygen consumption in the droplets commenced with the preparation of an aqueous solution with the bacteria, the culture medium and a suitable quantity of nanoparticles. The mixture was injected into the microfluidic system constructed of tubing with Teflon connectors with correspondingly shaped channels. The first module formed droplets with a volume of approx. 4 microlitres, which were directed to the incubation tube wound on a spool. In the middle of its length there was another module, with detectors for measuring oxygen and absorbance.

“In the incubation part in one phase of the cycle the droplets flowed in one direction, in the second – in another, electronically controlled by means of suitable solenoid valves. All this looks seemingly simple enough, but in practice one of the biggest challenges was to ensure a smooth transition between the detection module and the tubing, so that bacterial contamination did not occur at the connections,” explains PhD student Horka.

During their passage through the detection module the droplets flowed under an optical sensor which measured the so-called optical density, which is the standard parameter used to evaluate the number of cells (the more bacteria in the droplets, the less light passes through them). In turn, the measurement of the duration of the phosphorescence of the nanoparticles, evaluating the concentration of oxygen in the microdroplets, was carried out using the Piccolo2 optical detector, provided by the Austrian group. This detector, which looks like a big pen drive, was connected directly to the USB port on the control computer. Comparing information from both sensors, IPC PAS researchers showed that the microfluidic device they had constructed made it possible to regularly and quickly monitor the metabolic activity of bacteria in the individual microdroplets.

“We carried out our tests both with bacteria floating in water singly – this is how the common Escherichia coli bacteria behave – as well as with those having a tendency to stick together in clumps – as is the case for tuberculosis bacilli or others belonging to the same family including Mycobacterium smegmatis which we studied. Evaluation of the rate of oxygen consumption by both species of microorganisms proved to be not only possible, but also reliable,” stresses PhD student Artur Ruszczak (IPC PAS).

The results of the research, funded by the European ERC Starting Grant (Polish side) and the Maria Sklodowska-Curie grant (Austrian side) are an important step in the process of building fully functional microfluidic devices for conducting biological experiments lasting many weeks. A system for culturing bacteria in microdroplets was developed at the IPC PAS a few years ago, however it was constructed on a polycarbonate plate. The maximum dimensions of the plate did not exceed 10 cm, which greatly limited the number of droplets; in addition, as a result of interaction with the polycarbonate, after four days the channels were contaminated with bacteria. Devices of Teflon modules and tubing would not have these disadvantages, and would be suitable for practical applications.

Here’s a link to and a citation for the paper,

Lifetime of Phosphorescence from Nanoparticles Yields Accurate Measurement of Concentration of Oxygen in Microdroplets, Allowing One To Monitor the Metabolism of Bacteria by Michał Horka, Shiwen Sun, Artur Ruszczak, Piotr Garstecki, and Torsten Mayr. Anal. Chem., 2016, 88 (24), pp 12006–12012 DOI: 10.1021/acs.analchem.6b03758 Publication Date (Web): November 23, 2016

Copyright © 2016 American Chemical Society

This paper is behind a paywall.

Making lab-on-a-chip devices more accurate

An April 4, 2016 news item on phys.org announces research that will improve control and manipulation of the fluids in a lab-on-a-chip,

Lab-on-a-chip designates devices that integrate various biochemical functions on a fingernail-sized chip to enable quick and compact biological analysis or medical diagnosis by processing a small volume of biological samples, such as a drop of blood. To operate various functions on a lab-on-a-chip device, the key technology is the precise and rapid manipulation of fluid on a micro-scale.

A March 31, 2016 Pohang University of Science and Technology (POSTECH; South Korea) press release (also on EurekAlert), which originated the news item, expands on the theme,

In microfluidic devices, very small and trivial variables can frequently cause a large amount of errors. Up until now, Proportional-Integral-Derivative (PID) controller has normally been used for the manipulation of fluids in microfluidic chips. To apply the PID controller, a tedious gain-tuning process is required but the gain-tuning is a difficult process for people who are unfamiliar with control theory. Especially, in the case of controlling multiple flows, the process is extremely convoluted and frustrating.

The developed control algorithm can improve accuracy and stability of flow regulation in a microfluidic network without requiring any tuning process. With this algorithm, microfluidic flows in multiple channels can be controlled in simultaneous and independent way. The team expects that this algorithm has the potential for many applications of lab-on-a-chip devices. For example, cell culture or biological analysis, which are conducted in biology laboratories, can be performed on a microfluidic chip. Physical and chemical responses can be analyzed in the subdivided levels.

Here’s a link to and a citation for the paper,

Tuning-free controller to accurately regulate flow rates in a microfluidic network by Young Jin Heo, Junsu Kang, Min Jun Kim, & Wan Kyun Chung. Scientific Reports 6, Article number: 23273 (2016) doi:10.1038/srep23273 Published online: 18 March 2016

This is an open access paper.

Diagnostics on a credit card?

Diagnostic equipment keeps getting smaller with the latest being the size of a credit card (more or less). It’s called an ‘mChip’ and can be used to diagnose either HIV or syphillis. From the August 2, 2011 article by Ariel Schwartz on Fast Company,

If you were concerned you had HIV (and lived in America), it would be easy enough to get some blood drawn at a clinic near your house, and wait a few days (or even hours) for the results. But in Africa, many clinics and hospitals have to send out blood samples to a national lab. It’s a process that can take weeks, and patients in remote areas sometimes don’t even bother to make the trek back to the clinic to get results. On a continent with a rampant HIV epidemic, this is a big problem. But Columbia University researchers have a partial solution–a $1 plastic chip that can diagnose HIV and syphilis in 15 minutes.

The “mChip”, a credit-card-sized piece of plastic that is produced using a plastic injection molding process, tests for multiple diseases with just one pinprick of blood.

The international team working on this project was led by professor of bioengineering at Columbia University, Samuel Sia. Field testing of the mChip took place in Rwanda. GrrlScientist in her August 3, 2011 posting (at the Guardian Science blogs site) offers more technical details,

“The microfluidic design is very simple”, said Dr Sia. “It’s essentially a .. linear channel that’s been looped around in various ways.”

… This credit card-sized cassette is manufactured from plastic and each mChip cassette can test seven samples (one per channel), and requires no moving parts, electricity or external instrumentation. Instead, it has small holes moulded into the plastic so reagent-loaded tubes can be attached. …

The principles for how the mChip work are well known, straightforward and, quite frankly, beautiful.

The mChip can be used for other diagnostic tests. A prostate cancer testing mChip has already been approved for use and other tests are being developed as well.

Sia’s team is not the only one working on faster, cheaper, more reliable diagnostic tests. A team at the University of Georgia (US)  has just published research about their flu detection test (from the August 3, 2011 news item on Nanowerk),

A new detection method developed at the University of Georgia and detailed in the August edition of the journal Analyst (“One-step assay for detecting influenza virus using dynamic light scattering and gold nanoparticles”), however, offers the best of both worlds. By coating gold nanoparticles with antibodies that bind to specific strains of the flu virus and then measuring how the particles scatter laser light, the technology can detect influenza in minutes at a cost of only a fraction of a penny per exam.

“We’ve known for a long time that you can use antibodies to capture viruses and that nanoparticles have different traits based on their size,” said study co-author Ralph Tripp, Georgia Research Alliance Eminent Scholar in Vaccine Development in the UGA College of Veterinary Medicine. “What we’ve done is combine the two to create a diagnostic test that is rapid and highly sensitive.”

Sia’s team seems to have worked on both the test and diagnostic device whereas some teams like the one in Georgia focus on tests or like the team at Stanford (mentioned in my March 1, 2011 posting about their nanoLAB) focus on the device.

Not all of these new handheld diagnostic tools and tests are designed for disease identification. Argento (mentioned in my February 15, 2011 posting) is being used by UK Sport to assist their elite athletes prior to the 2012 Olympics.  Locally, i.e., in Vancouver, there’s a team at St. Paul’s Hospital, PROOF (mentioned in my Feb. 15, 2011 posting), working on a test that would eliminate the need for monthly biopsies for patients who have received kidney transplants.

Jello, microsystems, and kids

It’s a little outside my usual topic range but I’m extending the category since I’ve done it before just because I felt like it and because one of the moving forces behind this project (Eric Lagally) is a member of the Microsystems and Nanotechnology Group at the University of British Columbia (Canada). Lagally and his colleagues have devised a safe and inexpensive way for kids to make microfluidic devices. From the news item on Nanowerk,

Microfluidics, they [Lagally and colleagues] note, has the potential to revolutionize medicine and biology, reducing an entire laboratory of instruments for analyzing blood, urine, and other materials to the size of a postage stamp. Until now, however, hands-on experience with microfluidics has been impossible because of the expense and potentially toxic chemicals involved in making microfluidic devices.

The article [in ACS’ Analytical Chemistry “Using Inexpensive Jell-O Chips for Hands-On Microfluidics Education“] describes using Popsicle-type craft sticks taped to the bottom of a Styrofoam plate to form large-scale versions of the minute channels in actual microfluidic devices.

This sounds like the kind of thing you could do at home.  Bravo!