Spreading depolarizations occur spontaneously and frequently in injured human brain. They propagate slowly through injured tissue often cycling around a local area of damage. Tissue recovery after an spreading depolarization requires greatly augmented energy utilisation to normalise ionic gradients from a virtually complete loss of membrane potential. In the injured brain, this is difficult because local blood flow is often low and unreactive. In this study, we use a new variant of microdialysis, continuous on-line microdialysis, to observe the effects of spreading depolarizations on brain metabolism. The neurochemical changes are dynamic and take place on the timescale of the passage of an spreading depolarization past the microdialysis probe. Dialysate potassium levels provide an ionic correlate of cellular depolarization and show a clear transient increase. Dialysate glucose levels reflect a balance between local tissue glucose supply and utilisation. These show a clear transient decrease of variable magnitude and duration. Dialysate lactate levels indicate non-oxidative metabolism of glucose and show a transient increase. Preliminary data suggest that the transient changes recover more slowly after the passage of a sequence of multiple spreading depolarizations giving rise to a decrease in basal dialysate glucose and an increase in basal dialysate potassium and lactate levels.
Rapid and inexpensive serological tests for SARS-CoV-2 antibodies are needed to conduct
population-level seroprevalence surveillance studies and can improve diagnostic
reliability when used in combination with viral tests. Here, we report a novel low-cost
electrochemical capillary-flow device to quantify IgG antibodies targeting SARS-CoV-2
nucleocapsid proteins (anti-N antibody) down to 5 ng/mL in low-volume (10 μL)
human whole blood samples in under 20 min. No sample preparation is needed as the device
integrates a blood-filtration membrane for on-board plasma extraction. The device is
made of stacked layers of a hydrophilic polyester and double-sided adhesive films, which
create a passive microfluidic circuit that automates the steps of an enzyme-linked
immunosorbent assay (ELISA). The sample and reagents are sequentially delivered to a
nitrocellulose membrane that is modified with a recombinant SARS-CoV-2 nucleocapsid
protein. When present in the sample, anti-N antibodies are captured on the
nitrocellulose membrane and detected via chronoamperometry performed on a screen-printed
carbon electrode. As a result of this quantitative electrochemical readout, no result
interpretation is required, making the device ideal for point-of-care (POC) use by
non-trained users. Moreover, we show that the device can be coupled to a near-field
communication potentiostat operated from a smartphone, confirming its true POC
potential. The novelty of this work resides in the integration of sensitive
electrochemical detection with capillary-flow immunoassay, providing accuracy at the
point of care. This novel electrochemical capillary-flow device has the potential to aid
the diagnosis of infectious diseases at the point of care.
Developing tools
that are able to monitor transient neurochemical
dynamics is important to decipher brain chemistry and function. Multifunctional
polymer-based fibers have been recently applied to monitor and modulate
neural activity. Here, we explore the potential of polymer fibers
comprising six graphite-doped electrodes and two microfluidic channels
within a flexible polycarbonate body as a platform for sensing pH
and neurometabolic lactate. Electrodes were made into potentiometric
sensors (responsive to pH) or amperometric sensors (lactate biosensors).
The growth of an iridium oxide layer made the fiber electrodes responsive
to pH in a physiologically relevant range. Lactate biosensors were
fabricated via platinum black growth on the fiber electrode, followed
by an enzyme layer, making them responsive to lactate concentration.
Lactate fiber biosensors detected transient neurometabolic lactate
changes in an in vivo mouse model. Lactate concentration changes were
associated with spreading depolarizations, known to be detrimental
to the injured brain. Induced waves were identified by a signature
lactate concentration change profile and measured as having a speed
of ∼2.7 mm/min (
n
= 4 waves). Our work highlights
the potential applications of fiber-based biosensors for direct monitoring
of brain metabolites in the context of injury.
Currently,
there is a severe shortage of donor kidneys that are
fit for transplantation, due in part to a lack of adequate viability
assessment tools for transplant organs. This work presents the integration
of a novel wireless two-channel amperometric potentiostat with microneedle-based
glucose and lactate biosensors housed in a 3D printed chip to create
a microfluidic biosensing system that is genuinely portable. The wireless
potentiostat transmits data via Bluetooth to an Android app running
on a tablet. The whole miniaturized system is fully enclosed and can
be integrated with microdialysis to allow continuous monitoring of
tissue metabolite levels in real time. We have also developed a wireless
portable automated calibration platform so that biosensors can be
calibrated away from the laboratory and in transit. As a proof of
concept, we have demonstrated the use of this portable analysis system
to monitor porcine kidneys for the first time from organ retrieval,
through warm ischemia, transportation on ice, right through to cold
preservation and reperfusion. The portable system is robust and reliable
in the challenging conditions of the abattoir and during kidney transportation
and can detect clear physiological changes in the organ associated
with clinical interventions.
The COVID-19 pandemic focused attention on a pressing need for fast, accurate, and
low-cost diagnostic tests. This work presents an electrochemical capillary driven
immunoassay (eCaDI) developed to detect SARS-CoV-2 nucleocapsid (N) protein. The
low-cost flow device is made of polyethylene terephthalate (PET) and adhesive films.
Upon addition of a sample, reagents and washes are sequentially delivered to an
integrated screen-printed carbon electrode for detection, thus automating a full
sandwich immunoassay with a single end-user step. The modified electrodes are sensitive
and selective for SARS-CoV-2 N protein and stable for over 7 weeks. The eCaDI was tested
with influenza A and Sindbis virus and proved to be selective. The eCaDI was also
successfully applied to detect nine different SARS-CoV-2 variants, including
Omicron.
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