Year: 2018

A Technology Networks article based on NIH-funded research describes how organ-on-a-chip microfluidic devices just reached the US’ NASA portion of the International Space Station (ISS), the ISS National Lab, last Wednesday as part of an investigation into the effects of aging, mimicked by weightlessness, on the immune system.  The research team is led by Professor Sonja Schrepfer at UC-SF.

The immune system chips incorporate immune, bone marrow and blood vessel cells.  The physiological effects of space flight on astronauts, and the tissues on these chips, are similar to those of aging, including bone and muscle loss and altered immune systems.  The several dozen chips will be incubated for 2 weeks, and then frozen until they return to Earth for analysis at the Schrepfer lab.  Future SpaceX re-supply missions to the ISS in March and April 2019 will bring kidney, bone/cartilage, and blood/brain barrier chip sets as part of the same research programme.

It is hoped that the research may provide better understanding of, and potentially improved therapies for the process of aging.

Impressive research relating to Alzheimer’s disease (AD) research on a microfluidic platform recently emerged from the Cho group at the University of North Carolina at Charlotte and the Tanzi group at the Massachusetts General Hospital & Harvard Medical School; it was published in Nature Neuroscience and highlighted in a News Medical Lifesciences article.

The work describes a flexible microfluidic system that allows the effectiveness of different AD treatment drug compounds to be evaluated based on the responses of different types of brain cells, particularly the microglia cells involved in the brain & CNS immune response.  The microfluidic device contains 2 chambers, one with neuron cells and astrocytes, and the other with microglia.  Reduced microglia ‘recruitment’ by the other cells, as visualised in the channels between the chambers, via excreted cytokines by the neuron and astrocyte cells indicates reduced neuronal damage and, presumably, reduced loss of memory or other mental capacity.

There are over 3000 approved drug compounds for treatment of Alzheimer’s disease, according to Joseph Park, first author on the research paper, so evaluation in a representative biological and disease environment such as created in their chip is crucial.  Human trials are lengthy, expensive and carry risk for the participants.  Selection of the most promising candidates for drug therapy through understanding their interaction with brain cells in this microfluidic system offers promise to accelerate the pace towards effective treatments of Alzheimer’s disease.

Research from Zhonghua Ni‘s group at Southeast University in China published recently in Analytical Chemistry (DOI: 10.1021/acs.analchem.8b02201) allows for effective cell concentration along a spiral microfluidic channel.

The device is connected directly to a syringe, and outward flow in the microfluidic spiral channel is generated simply by the operator pushing on the plunger.  Separation by inertial (centrifugal) forces partitions the cells to the inside channel ‘track’ such that a Y-shaped bifurcation at the outer spiral terminus yields a concentrated cell suspension on the inner outlet and almost cell-free solution on the outer outlet.

The device embodies simplicity as a virtue.  It has no active components, and requires no electrical power, only average human thumb power :-); it simply requires a sample-filled syringe and two collection vials.  It is well conceived for both resource-poor and lab environments alike.  Their bold claim that one could bring their concentrator “into commercial outcomes without additional redesigning” initially made me chuckle, but after absorbing their work, I have to admit they appear to be exaggerating only slightly!  An Abbott, BD or start-up would require some industrial product design, but technically, they appear to be at the finish line.  I can’t speak to the competition in this product segment, and sure hope they have a good patent, but it seems pretty clever!

An interesting review of lab-on-a-chip devices made on flexible substrates was recently published in Lab on a Chip by Anastasios Economou and Christos Kokkinos at the University of Athens, and Mamas Prodromidis at the University of Ioannina.  The authors cover devices made on polymer, paper and textile fabric substrates and which use electrochemical biosensing for detection.  Lab-on-a-chip & microfluidic devices based on flexible substrates are very attractive given the low costs of the substrate and deposited materials, inexpensive and well established high volume manufacturing processes, and physical flexibility as an attribute for body-wearable devices.

Sensor/device formats include patches, bandages and wristbands for dermal/transdermal sensing, dental mouthgards for salivary analyses, tooth patches for bacterial detection and contact lenses for tear fluid analysis.  Analytical applications include immunosensing, glucose monitoring, bovine serum albumin (BSA) sensing, metabolite sensing, cancer marker detection and HIV detection.  Deposition methods include lower-cost approaches such as screen printing, inkjet printing and electrodeposition for materials such as graphite, indium tin oxide, polyethylene terephthalate (PET).  Polymer substrates include thermoplastics like polyethylene, polystyrene, PET, polypropylene, polycarbonate, cyclic olefin (co)polymers (COC & COP), thermoset polymers like polyimide, and photoresists.  Filtre paper is the most common type of paper substrate, though newsprint is also mentioned.  3-D, folding or origami approaches are also discussed, as previously highlighted in this blog.

Fascinating new research by Felix Ellett and co-authors from Massachusetts General Hospital (MGH) and Harvard Medical School (HMS) shows elegant detection of sepsis in hospital patients via microfluidic blood analysis.  The study was published recently in Nature – Biomedical Engineering and profiled by MGH and Technology Networks.

Previous research from Daniel Irimia‘s group at MGH and HMS in 2014 showed that dysfunctional behaviour of neutrophils (a type of white blood cell) correlated well with sepsis.  This current research from his and Jarone Lee‘s (MGH) groups takes the next step and uses a microfluidic device to perform the analysis.  Their 5-mm device has 4.5-µm channel filtres (to screen out red blood cells) and meandering channel networks to allow the neutrophils to leave the sample drop of blood, and be observed in the microfluidic channel network.  Discrimination by neutrophil characteristics & behaviours (such as number of neutrophils, oscillations and motionless time in microfluidic channels, migration distance and tendency to migrate back to the central sample chamber) allowed the researchers to correctly predict the presence of sepsis in over 95% of patients in a small study of 19 ICU patients.

Detection of sepsis in patients is of critical importance.  According to the MGH and TN article profiles, about one million cases of sepsis occur annually in the US, with 25% of cases being fatal.  Comparable data from the UK showed that the mortality rate for hospital admissions with severe sepsis assessed withing the first 24 hours was 45%.  Current detection methods leave much to be desired, with misdiagnosis occurring in 30% of patients.  The arrival of fast, accurate diagnostic methods would lead to better patient outcomes, likely including saved lives.

Ground-breaking lab-on-a-chip research out of the van Nimwegen lab at the University of Basel, Switzerland and the Myers lab at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, has enabled both rapid environmental control of cell media, and the ability simultaneously monitor large numbers of bacteria as single cells.  The work, recently published in Nature Communications and highlighted in Technology Networks, describes a PDMS microfluidic device with ~1900 channels measuring ~ 1 x 1 x 25 µm that house the single cells, and which are connected perpendicularly to larger supply channels containing the cell medium solution.  The device also features continuously variable 2-input control of cell media via a split channel configuration, together with a mixing serpentine upstream of the smaller single cell channels.  New image analysis software was also created to handle the enormous amount of image data generated by this system when in operation.

The device is intended to provide a real-time monitoring window into gene regulation in bacteria, a laudable advance.  For example, bacterial response to different antibiotics can be measured, and insight into intra-cellular communication may be revealed.  The device’s performance was nicely illustrated in a video (image above from Nature Communications article) showing an experiment where gene regulation via the lactose operon was observed while alternating between glucose and lactose nutrients in the supply channel; green fluorescent protein can be seen to appear within 1-2 h of introducing the lactose-rich medium to the cells.

Fascinating research out of the Robinson, Kemere and Pasquali labs in Electrical & Computer Engineering and Chemistry Departments at Rice University, at Baylor College of Medicine and out of the Royer-Carfagni lab in Engineering at the University of Parma.  It was published recently in ACS NanoLetters and summarised in NewsMedical, and is focussed on the gentle introduction of microelectrodes for medical applications using microfluidics.  The team showed the insertion of carbon nanotube (CNT) electrodes into brain tissue surrogate (agarose gel) as well as rat brains, with subsequent observation of neural activity via these electrodes.  The ~30 µm CNT fibre is placed along the central channel in a glass/PDMS microfluidic device, and then carefully controlled sheath fluid flow is used to pull the wire down through a narrower ~100 µm-wide channel and into the tissue.  See impressive video showing microfluidic injection of CNT electrode into gel.

This technology is an excellent example of marrying microfluidics with nanotechnology, in this case for a medical application.  The microfluidic insertion of CNT electrodes in lieu of traditional approaches makes the process less damaging to surrounding brain tissue during insertion.  Neuro-sensing applications where gently introduced flexible CNT electrodes would be beneficial may include monitoring for epilepsy, repairing/patching connections for sight and hearing, as well as other areas of neuroscience research.