Serotonin is an important signaling molecule in the human body. The detection of serotonin is commonly performed by high performance liquid chromatography (HPLC), which is costly and time consuming ...due to extensive sample preparation. We will show that these problems can be overcome by using molecularly imprinted polymers (MIPs) as synthetic receptors in combination with impedance spectroscopy as readout technique. The MIPs were prepared with several blends of the underlying monomers and the best performing MIP material was selected by optical batch-rebinding experiments. MIP microparticles were then integrated in an impedimetric sensor cell and dose–response curves were measured in PBS buffer and in non-diluted blood plasma. The sensor provides reliable data in the physiologically relevant concentration regime as an independent validation by HPLC measurements demonstrates. Finally, we show that the impedimetric response upon serotonin binding can be attributed to a capacitive effect at the interface between the MIP particles and the plasma.
In this work, we present a new device to monitor the five main vital parameters of hospitalized patients: heart rate, respiratory rate, blood oxygen saturation, blood pressure and temperature. The ...device consists of one single unit placed on the chest with two electrodes connected to the patient. The device continuously acquires the electrocardiogram, 3-wavelength photoplethysmogram, bioimpedance, body temperature and 3-axis acceleration. These raw data are securely sent via a WiFi access point to a local server where algorithms are running to calculate the five vital parameters, combined with the level of activity and the posture. Alarms, live stream, and a real-time estimation of the early warning score used to assess the instantaneous state of a patient are available to nurses to react quickly and adequately if needed. Thanks to its small form factor and weight the device is worn unobtrusively by the patient who can move without being restrained by wires; a small battery ensures an autonomy of a few days. In this paper, the firmware and hardware architectures are detailed comprising the list of the sensors, the main chips used and the casing. The relationships between what the sensors measure and the vital parameters of interest are discussed.
•We describe a fabrication protocol for nanoscale, multichannel, interdigitated electrode arrays in a wafer scale process.•We combine nanoimprint lithography and classical photolithography to realize ...highly-reliable and reproducible sensor arrays.•In our process, by firstly replicating the expensive, nano-machined mold, we established a cost-effective and high throughput protocol.•We show that our devices are highly reliable from sensor spot to sensor spot and that they can be used as biosensors.•We describe the fabrication process in detail, a functional characterization and a first proof-of-concept application of our devices.
The continuous progress in the construction of advanced, miniaturized electrodes provides a promising route towards compact and sensitive biological and chemical sensor platforms. We present a combined micro- and nanofabrication process at wafer-scale with nanoimprint lithography and subsequent photolithography for the realization of ultra-small, interdigitated electrode arrays. Several chips of gold nanoelectrode arrays (NEA) in a 4 × 4 configuration designed as interdigitated electrodes (NEA-IDEs) with finger structures measuring 14 μm in length and 600 nm in width with 600 nm spacing were fabricated simultaneously on 4-inch wafers. Our process involved a nanoimprint lithography step, wet-etching, metal evaporation and nano lift-off followed by optical lithography for metal contact lines and passivation layers. The optimized procedure yielded high-quality NEA-IDEs with reliable electrochemical behavior as inferred from voltammetric and impedimetric analysis. The final array allows the control of all 16 NEA-IDEs in parallel, which can be beneficial for multi-analyte detection. In a proof-of-concept assay, to demonstrate the applicability of the NEA-IDEs for biosensing, the nanostructures were modified with short DNA molecules as recognition elements for the detection of hybridization via impedance spectroscopy. Stable impedance signals were found using the redox system ferri-/ferrocyanide. After hybridization with complementary target DNA the sensors showed an enhancement of the charge transfer resistance. Experiments with different target DNA concentrations demonstrated a dynamic detection range of 1–100 nM. The main advantage of these NEA-IDE structures is that they are small enough to be integrated into typical microchannel dimensions of 50–100 μm for miniaturized lab-on-a-chip biosensor devices in future.
In this work, we will present a novel approach for the detection of small molecules with molecularly imprinted polymer (MIP)-type receptors. This heat-transfer method (HTM) is based on the change in ...heat-transfer resistance imposed upon binding of target molecules to the MIP nanocavities. Simultaneously with that technique, the impedance is measured to validate the results. For proof-of-principle purposes, aluminum electrodes are functionalized with MIP particles, and
l
-nicotine measurements are performed in phosphate-buffered saline solutions. To determine if this could be extended to other templates, histamine and serotonin samples in buffer solutions are also studied. The developed sensor platform is proven to be specific for a variety of target molecules, which is in agreement with impedance spectroscopy reference tests. In addition, detection limits in the nanomolar range could be achieved, which is well within the physiologically relevant concentration regime. These limits are comparable to impedance spectroscopy, which is considered one of the state-of-the-art techniques for the analysis of small molecules with MIPs. As a first demonstration of the applicability in biological samples, measurements are performed on saliva samples spiked with
l
-nicotine. In summary, the combination of MIPs with HTM as a novel readout technique enables fast and low-cost measurements in buffer solutions with the possibility of extending to biological samples.
Figure
Heat-transfer based detection with molecularly imprinted polymers
The need for more advanced, accurate and lower cost sensor platforms is constantly growing. However, for certain applications the already existing sensing systems based on biological recognition ...elements have sometimes restrictions, which limit their use. As a result, sensors with synthetic recognition elements, such as molecular imprinted polymers (MIPs), can be interesting alternatives. Molecular imprinting leads to the formation of inert polymer particles with nanocavities, which can exhibit similar selectivity and specificity to target molecules as antibodies or enzymes. It is demonstrated that MIPs can be readily incorporated into two different sensor platforms for the detection of histamine in aqueous media. The first platform is based on electrochemical impedance spectroscopy and allows for the accurate detection of histamine in the nanomolar range. The second sensing technique is based on microgravimetry and allows for the detection of histamine in the micromolar range. Using the analogous molecule histidine, it is demonstrated that both sensor platforms are specific for the detection of histamine.
Poly(N‐isopropylacrylamide) (PNIPAAm) hydrogel films with incorporated graphene oxide (GO) were developed and tested as light‐stimulated actuators. GO dispersions were synthesized via Hummers method ...and characterized toward their optical properties and photothermal energy conversion. The hydrogels were prepared by means of photopolymerization. In addition, the influence of GO within the hydrogel network on the lower critical solution temperature (LCST) was investigated by differential scanning calorimetry (DSC). The optical absorbance and the response to illumination were determined as a function of GO concentration for thin hydrogel films. A proof of principle for the stimulation with light was performed.
authoren Graphene oxide (GO) nanoparticles were incorporated in temperature‐sensitive Poly(N‐isopropylacrylamide) (PNIPAAm) hydrogels. The nanoparticles increase the light absorption and convert ...light energy into heat efficiently. Thus, the hydrogels with GO can be stimulated spatially resolved by illumination as it was demonstrated by IR thermography. The temporal progression of the temperature maximum was detected for different concentrations of GO within the polymer network. Furthermore, the compatibility of PNIPAAm hydrogels with GO and cell cultures was investigated. For this purpose, culture medium was incubated with hydrogels containing GO and the viability and morphology of chinese hamster ovary (CHO) cells was examined after several days of culturing in presence of this medium.
Mimicking the selectivity and sensitivity of biological systems for sensor devices is of increasing interest in biomedical, environmental and chemical analysis. Synthetic materials with imprinted ...nanocavities, acting as highly selective artificial receptors, are a tailor-made solution in obtaining such a sensor. Incorporation of such molecularly imprinted polymers (MIPs) in a platform suitable for electrochemical measurements, can offer high sensitivity together with device miniaturization and an electronic read-out. As a proof of principle, a MIP-based sensor for
l-nicotine has been developed. To this end, the molecular structure of
l-nicotine was imprinted in a polymer matrix of polymethacrylic acid (PMAA). Subsequently, microparticles of the imprinted polymer were immobilized on thin films of the conjugated polymer OC
1C
10-PPV. These films were incorporated in an impedimetric sensing device. Using electrochemical impedance spectroscopy, the real part of the impedance was monitored for various concentrations. This setup allows for the detection of
l-nicotine from 1 to 10
nM and is insensitive for the resembling molecule
l-cotinine.
A new method to locally address and stimulate hydrogel‐based actuators in microfluidic channels with the help of a focused light source is presented by Breuer et al. (pp. 1368–1374). To create ...light‐stimulated actuators, poly(N‐isopropylacrylamide) (PNIPAAm) hydrogel films were modified by incorporation of graphene oxide (GO). For this, GO dispersions were synthesized and characterized towards their optical properties and photothermal energy conversion. In addition, the influence of GO within the hydrogel network on the lower critical solution temperature (LCST) was investigated by differential scanning calorimetry (DSC). The optical absorbance and the response to illumination with a light source were determined as a function of the GO concentration for thin hydrogel films. The results underline that a focused light beam can easily heat hydrogels modified with GO above their LCST. Thus, the new method avoids the need for heater or other supplementary structures as used in conventional hydrogel‐based actutators for microfluidic set‐ups. Therefore, this work provides a promising concept to create miniaturized externally addressable actuators in the future.
The pathogenesis of the Ebola virus which leads to a severe hemorrhagic fever in hosts is a very complex process which is not completely understood. Glycoproteins of the viral envelope are believed ...to play a crucial role in receptor binding and subsequently in fusion of the virus with the target cells of the host. As a result, the virus enters the cells and replicates. This process causes further cytopathic, and pathological reactions in the host's body. To gain further insights into the fusogenic interactions of the virus with cell membranes, we used well-controlled simple biomimetic systems, consisting of solid-supported phospholipid layers together with a small sequence of the viral glycoprotein (EBO17), which is believed to be the most important part responsible for viral pathogenesis. We monitor the real-time interaction of a EBO17 peptide sequence from the Ebola virus with dipalmitoylphosphatidylcholine (DMPC) phospholipid membranes using quartz crystal microbalance with dissipation monitoring (QCM-D) as a label-free method. In particular, we focus on the influence of the concentration of the peptide and the lipid layer geometry on the disrupting mechanism of the EBO17 peptide. Results indicate that for 2D supported lipid bilayers, low peptide concentrations induce a small, but detectable change in layer stability due to the presence of an α-helix configuration of the peptide. With large peptide concentrations, the peptide acquires a β-sheet configuration and no significant layer changes can be observed. A different mechanism is responsible for the interaction of the EBO17 peptides with the more complex 3D supported vesicle layers, for which a concentration-dependent trend can be observed leading to thicker lipid layers. Complementary analysis of the lipids' main phase transition evidences the differences induced in layer organization on the two layer geometries. These results confirm the importance of the interplay between lipid layer geometry and related peptide organization as an essential marker in peptide activity.
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