Inkjet printing of UV-curable adhesive and dielectric inks for microfluidic devices.

Bonding of polymer-based microfluidics to polymer substrates still poses a challenge for Lab-On-a-Chip applications. Especially, when sensing elements are incorporated, patterned deposition of adhesives with curing at ambient conditions is required. Here, we demonstrate a fabrication method for fully printed microfluidic systems with sensing elements using inkjet and stereolithographic 3D-printing.

Healthy term and moderately preterm infants have similar cerebral oxygen saturation and cerebral blood flow volumes during early post-natal transition.

AIM: This pilot study evaluated changes in regional cerebral oxygen saturation and cerebral blood flow volume during the transitional period in healthy term and moderately preterm infants. METHODS: The cohort comprised 16 preterm infants and seven full-term infants with mean gestational ages of 34 and 39 weeks, respectively. Longitudinal measurements were conducted during the first three days after birth. Regional cerebral oxygen saturation was determined bilaterally by frequency domain near-infrared spectroscopy. Flow volumes were determined in internal carotid and vertebral arteries by multiplying the time-averaged velocity by the cross-sectional area: cerebral blood flow volume was calculated as the sum of flow volumes and adjusted for brain weight. RESULTS: Brain weight-adjusted cerebral blood flow volumes and regional cerebral oxygen saturation were similar in preterm and term infants. Regional cerebral oxygen saturation did not correlate with brain weight-adjusted cerebral blood flow volume. Right and left brain weight-adjusted internal carotid flow volumes did not correlate with right and left regional cerebral oxygen saturation. CONCLUSION: Our findings suggest that during the first three days after birth there was adequate cardiorespiratory adaptation, cerebral perfusion and adequate compensation through the arterial circle of Willis in both healthy term and moderately preterm infants.

Enzyme logic AND-Reset and OR-Reset gates based on a field-effect electronic transducer modified with multi-enzyme membrane.

Capacitive field-effect sensors modified with a multi-enzyme membrane have been applied for an electronic transduction of biochemical signals processed by enzyme-based AND-Reset and OR-Reset logic gates. The local pH change at the sensor surface induced by the enzymatic reaction was used for the activation of the Reset function for the first time.

Electrical monitoring of polyelectrolyte multilayer formation by means of capacitive field-effect devices.

The semiconductor field-effect platform represents a powerful tool for detecting the adsorption and binding of charged macromolecules with direct electrical readout. In this work, a capacitive electrolyte-insulator-semiconductor (EIS) field-effect sensor consisting of an Al-p-Si-SiO2 structure has been applied for real-time in situ electrical monitoring of the layer-by-layer formation of polyelectrolyte (PE) multilayers (PEM). The PEMs were deposited directly onto the SiO2 surface without any precursor layer or drying procedures. Anionic poly(sodium 4-styrene sulfonate) and cationic weak polyelectrolyte poly(allylamine hydrochloride) have been chosen as a model system. The effect of the ionic strength of the solution, polyelectrolyte concentration, number and polarity of the PE layers on the characteristics of the PEM-modified EIS sensors have been studied by means of capacitance-voltage and constant-capacitance methods. In addition, the thickness, surface morphology, roughness and wettabilityof the PE mono- and multilayers have been characterised by ellipsometry, atomic force microscopy and water contact-angle methods, respectively. To explain potential oscillations on the gate surface and signal behaviour of the capacitive field-effect EIS sensor modified with a PEM, a simplified electrostatic model that takes into account the reduced electrostatic screening of PE charges by mobile ions within the PEM has been proposed and discussed.

Chip-based amperometric enzyme sensor system for monitoring of bioprocesses by flow-injection analysis.

A microfluidic chip integrating amperometric enzyme sensors for the detection of glucose, glutamate and glutamine in cell-culture fermentation processes has been developed. The enzymes glucose oxidase, glutamate oxidase and glutaminase were immobilized by means of cross-linking with glutaraldehyde on platinum thin-film electrodes integrated within a microfluidic channel. The biosensor chip was coupled to a flow-injection analysis system for electrochemical characterization of the sensors. The sensors have been characterized in terms of sensitivity, linear working range and detection limit. The sensitivity evaluated from the respective peak areas was 1.47, 3.68 and 0.28 µAs/mM for the glucose, glutamate and glutamine sensor, respectively. The calibration curves were linear up to a concentration of 20 mM glucose and glutamine and up to 10 mM for glutamate. The lower detection limit amounted to be 0.05 mM for the glucose and glutamate sensor, respectively, and 0.1 mM for the glutamine sensor. Experiments in cell-culture medium have demonstrated a good correlation between the glutamate, glutamine and glucose concentrations measured with the chip-based biosensors in a differential-mode and the commercially available instrumentation. The obtained results demonstrate the feasibility of the realized microfluidic biosensor chip for monitoring of bioprocesses.

[2-year follow-up examinations (Bayley II) in infants born at <32 weeks in a German perinatal center]. / 2-Jahres-Nachuntersuchung (Bayley) sehr kleiner Frühgeborener der Jahrgänge 2004-2007: Ergebnisse und Vollständigkeitsanalyse eines Perinatalzentrums.

BACKGROUND: Since 2008, follow-up examinations at 2 years of age with the standardized Bayley II test have become obligatory in Germany for all very low birth weight infants. AIM: We already performed such examinations before 2006. Here, we compared our data and the completeness of our examinations before and after the introduction of the obligatory 2-year follow-up. PATIENTS: From 2004-2007, 372 infants <1500 g or <32 weeks were discharged alive from our center, 19 infants died during their initial hospital stay, 2 after discharge. RESULTS: 271 patients participated in the follow-up examination at age 2 years, with the proportion of participating infants increasing from 64% to 84% after the introduction of obligatory tests. 75% of infants showed a normal development, while 4% had a severe impairment (defined as being blind (1), deaf (1) or having cerebral palsy (6), the CP rate thus being 2%). 49% of infants completed the Bayley test; the mean MDI was 100.3 (SD 10.6). There were no significant qualtitative differences in test results with the introduction of the obligatory test. CONCLUSIONS: The completeness of our follow-up increased over the years. In comparison with international data we found a low rate of severely impaired, deaf or blind VLBW infants.

Rapid assessment of the stability of DNA duplexes by impedimetric real-time monitoring of chemically induced denaturation.

In this article, we report on the electronic monitoring of DNA denaturation by NaOH using electrochemical impedance spectroscopy in combination with fluorescence imaging as a reference technique. The probe DNA consisting of a 36-mer fragment was covalently immobilized on nanocrystalline-diamond electrodes and hybridized with different types of 29-mer target DNA (complementary, single-nucleotide defects at two different positions, and a non-complementary random sequence). The mathematical separation of the impedimetric signals into the time constant for NaOH exposure and the intrinsic denaturation-time constants gives clear evidence that the denaturation times reflect the intrinsic stability of the DNA duplexes. The intrinsic time constants correlate with calculated DNA-melting temperatures. The impedimetric method requires minimal instrumentation, is label-free and fast with a typical time scale of minutes and is highly reproducible. The sensor electrodes can be used repetitively. These elements suggest that the monitoring of chemically induced denaturation at room temperature is an interesting approach to measure DNA duplex stability as an alternative to thermal denaturation at elevated temperatures, used in DNA-melting experiments and single nucleotide polymorphism (SNP) analysis.

An array of field-effect nanoplate SOI capacitors for (bio-)chemical sensing.

An array of individually addressable nanoplate field-effect capacitive (bio-)chemical sensors based on an SOI (silicon-on-insulator) structure has been developed. The isolation of the individual capacitors was achieved by forming a trench in the top Si layer with a thickness of 350 nm. The realized sensor array allows addressable biasing and electrical readout of multiple nanoplate EISOI (electrolyte-insulator-silicon-on-insulator) capacitive biosensors on the same SOI chip as well as differential-mode measurements. The feasibility of the proposed approach has been demonstrated by realizing sensors for the pH and penicillin concentration detection as well as for the label-free electrical monitoring of polyelectrolyte multilayers formation and DNA (deoxyribonucleic acid)-hybridization event. A potential change of ∼ 120 mV has been registered after the DNA hybridization for the sensor immobilized with perfectly matched single-strand DNA, while practically no signal changes have been observed for a sensor with fully mismatched DNA. The realized examples demonstrate the potential of the nanoplate SOI capacitors as a new basic structural element for the development of different types of field-effect biosensors.

Field-effect devices for detecting cellular signals.

The integration of living cells together with silicon field-effect devices challenges a new generation of biosensors and bioelectronic devices. Cells are representing highly organised complex systems, optimised by millions of years of evolution and offering a broad spectrum of bioanalytical receptor "tools" such as enzymes, nucleic acids proteins, etc. Their combination with semiconductor-based electronic chips allows the construction of functional hybrid systems with unique functional and electronic properties for both fundamental studies and biosensoric applications. This review article summarises recent advances and trends in research and development of cell/transistor hybrids (cell-based field-effect transistors) as well as light-addressable potentiometric sensors.

Characterisation of capacitive field-effect sensors with a nanocrystalline-diamond film as transducer material for multi-parameter sensing.

The feasibility of a capacitive field-effect EDIS (electrolyte-diamond-insulator-semiconductor) platform for multi-parameter sensing is demonstrated by realising EDIS sensors with an O-terminated nanocrystalline-diamond (NCD) film as transducer material for the detection of pH and penicillin concentration as well as for the label-free electrical monitoring of adsorption and binding of charged macromolecules, like polyelectrolytes. The NCD films were grown on p-Si-SiO(2) substrates by microwave plasma-enhanced chemical vapour deposition. To obtain O-terminated surfaces, the NCD films were treated in an oxidising medium. The NCD-based field-effect sensors have been characterised by means of constant-capacitance method. The average pH sensitivity of the O-terminated NCD film was 40 mV/pH. A low detection limit of 5 microM and a high penicillin G sensitivity of 65-70 mV/decade has been obtained for an EDIS penicillin biosensor with the adsorptively immobilised enzyme penicillinase. Alternating potential changes, having tendency to decrease with increasing the number of adsorbed polyelectrolyte layers, have been observed after the layer-by-layer deposition of polyelectrolyte multilayers, using positively charged PAH (poly (allylamine hydrochloride)) and a negatively charged PSS (poly (sodium 4-styrene sulfonate)) as a model system. The response mechanism of the developed EDIS sensors is discussed.

[Intracerebral bleeding as the first symptom of a congenital anaplastic astrocytoma]. / Eine intrazerebrale Blutung als Initialsymptom eines konnatalen anaplastischen Astrozytoms.

BACKGROUND: Anaplastic astrocytomas in neonates are extremely rare. Newborns, however, often have neuroectodermal central nervous tumours. CASE REPORT: We report about a female term newborn (birth weight 3,600 g, APGAR 9/10/10), who had shrill screams, intermittent shivering and bradycardia. An ultrasound scan of the brain showed an intracerebral bleeding. Therefore, the child was transferred to the intensive care unit of our hospital. A CT scan showed cerebral bleeding in the left parieto-occipital region, partially clotted, with a space-demanding effect. The intracerebral bleeding in the left occipital region was cleared out. No tumour was found, but an anaplastic astrocytoma (WHO Grade III) was diagnosed histologically. Serial ultrasound investigations of the brain showed a normal midline and a redevelopment of the left-sided ventricle. After surgery no tumour was visible in the MRI. Six weeks later, a tumour was found in the area of the initial bleeding region on MRI. CONCLUSION: Congenital anaplastic astrocytomas have a variable outcome, with different survival rates as compared to adults. In the literature, survival rates of 36-50 % were found after complete tumour resection. In cases of neonatal intracerebral bleeding, a tumour might be the cause of the haemorrhage.

Field-effect sensors with charged macromolecules: characterisation by capacitance-voltage, constant-capacitance, impedance spectroscopy and atomic-force microscopy methods.

Field-effect-based capacitive electrolyte-insulator-semiconductor (EIS) sensors have been utilised for the deoxyribonucleic acid (DNA) immobilisation and hybridisation detection as well as for monitoring the layer-by-layer adsorption of polyelectrolytes (anionic poly(sodium 4-styrene sulfonate) (PSS) and cationic poly(allylamine hydrochloride) (PAH)). The EIS sensors with charged macromolecules have been systematically characterised by capacitance-voltage, constant-capacitance, impedance spectroscopy and atomic-force microscopy methods. The effect of the number and polarity of the polyelectrolyte layers on the shift of the capacitance-voltage curves has been investigated. Alternating potential shifts of about 30-90 mV have been observed after the adsorption of each polyanion and polycation layer, respectively. The DNA immobilisation and hybridisation signals were 35-55 and 24-33 mV, respectively. The possible mechanisms for the sensor responses are discussed.

Label-free detection of single nucleotide polymorphisms utilizing the differential transfer function of field-effect transistors.

We present a label-free method for the detection of DNA hybridization, which is monitored by non-metallized silicon field-effect transistors (FET) in a microarray approach. The described method enables a fast and fully electronic readout of ex situ binding assays. The label-free detection utilizing the field-effect is based on the intrinsic charge of the DNA molecules and/or on changes of the solid-liquid interface impedance, when biomolecules bind to the sensor surface. With our sensor system, usually a time-resolved, dc readout is used. In general, this FET signal suffers from sensor drift, temperature drift, changes in electrolyte composition or pH value, influence of the reference electrode, etc. In this article, we present a differential ac readout concept for FET microarrays, which enables a stable operation of the sensor against many of these side-parameters, reliable readout and a possibility for a quick screening of large sensor arrays. We present the detection of point mutations in short DNA samples with this method in an ex situ binding assay.

The light-addressable potentiometric sensor for multi-ion sensing and imaging.

The light-addressable potentiometric sensor (LAPS) is a semiconductor-based chemical sensor with an electrolyte-insulator-semiconductor structure. The LAPS can have many measuring points integrated on the sensing surface, which are individually accessed by a light beam. By modifying the measuring points with different materials, a single sensor plate can be used as a multi-analyte sensor. In this paper, instrumentation and application of LAPS to multi-ion sensing and imaging are described. As a new application of LAPS, potentiometric imaging of a microfluidic channel is proposed.

A novel TITF-1 mutation causes benign hereditary chorea with response to levodopa.

Presented is a pedigree with infancy-onset benign hereditary chorea (BHC) caused by a novel nonsense mutation in exon 3 (523G-->T, E175X) of the TITF-1 (Nkx2.1) gene. Four confirmed mutation carriers showed the typical movement disorder of BHC and congenital hypothyroidism. Surprisingly, treatment with levodopa improved gait dramatically and reduced chorea in two patients. Dopaminergic drugs should be considered a useful therapeutic option in BHC.

MRI for the management of neonatal cerebral infarctions: importance of timing.

PURPOSE: Focal ischemic stroke in neonates is a rare occurrence. Diagnosis with most imaging modalities is difficult, but necessary for initiating an anticoagulatory treatment. The purpose of this study was to evaluate the sensitivity of MRI sequences within the first 14 days of birth. PATIENTS AND METHODS: Four patients with neonatal stroke presenting as seizures were examined using a standard MRI protocol including diffusion-weighted images (DWI) and magnetic resonance angiography (MRA) within 72 h of birth. The time between the onset of symptoms and MRI ranged from 6 h to 48 h. Follow-up examinations were performed on days 5 ( n=1), 7 ( n=2), and 14 ( n=1) for the control of a treatment with low-molecular heparin. RESULTS: Eight infarctions were detected in the four patients, 5 in the middle cerebral artery (MCA), three in the posterior cerebral artery (PCA) territory. All lesions were visible using DWI, four on T2-weighted images. Whereas in two patients small lesions contralateral to a large stroke were missed on T2-weighted images, the diagnosis would have been missed altogether without DWI in one patient. On follow-up, the visibility of the infarctions had declined using DWI after 5 days and the lesions were invisible after 1 week. Fourteen days after the stroke, an increased diffusion was detected in the infarcted brain tissue. By this time, all lesions were visible on T2-weighted images. CONCLUSION: In neonates, infarcted brain tissue can be detected using DWI with high sensitivity during the first 2 days after stroke and before other sequences are diagnostic. However, the diffusion restriction does not persist beyond 1 week. After 5 days, diagnosis has to rest mainly on T2-weighted images.

The development of cerebral perfusion in healthy preterm and term neonates.

Quantitative measurement of cerebral blood flow (CBF) volume was performed by sonographic flowmetry of both internal carotid (ICA) and vertebral arteries (VA) in 113 healthy preterm and term infants of 32 - 42 weeks postmenstrual age (PA) in order to delineate the physiological characteristics of brain perfusion in a time period very sensitive to brain injury. Mean CBF volume increased with PA, beginning with 33 +/- 9 ml/min in neonates of 32 - 34 weeks and rising to 45 +/- 10, 58 +/- 13, 69 +/- 14, and 83 +/- 16 ml/min, respectively, in the PA groups of 35 - 36, 37 - 38, 39 - 40 and 41 - 42 weeks. There was no difference in CBF volume between the sexes. The bilateral sum of flow volumes in both ICA and VA rose markedly with PA. The relative contribution of bilateral VA flow volume to total CBF volume was 26 +/- 8 % and remained constant with PA. In addition, we calculated the approximate CBF (ml/100 g brain weight/min) using the brain weights of each child as estimated by means of an equation based on head circumference measurements. Estimated CBF correlated significantly with PA (r = 0.49; p

Isolated internal cerebral venous thrombosis in a neonate with increased lipoprotein (a) level: diagnostic and therapeutic considerations.

Background. Internal cerebral venous thrombosis is a life-threatening condition, which requires immediate therapy. Being infrequent in childhood, internal venous thrombosis is very rare in the neonate and has never been observed without concomitant occlusion of further dural sinuses. Case Description. We report a neonate born at term, who developed seizures on the third day of life after normal pregnancy and uneventful delivery. Ultrasound and CT disclosed bilateral intraventricular and intracerebral hemorrhage with an unusual distribution for germinal matrix hemorrhage. MRI disclosed thrombotic occlusion of the straight sinus and the internal cerebral veins with concomitant bleeding into the ventricles, the basal ganglia, thalamus and the periventricular hemispheres. The other sinuses were not affected. The clinical condition of the child improved after initiation of a low-dose heparin treatment with subsequent partial recanalization of the occluded vessels. The screening for risk factors disclosed an elevated lipoprotein (a) level, also present in both parents. Conclusion. Internal cerebral venous thrombosis may be encountered in neonates and must be included in the list of differential diagnosis of perinatal intraventricular and intracerebral bleeding. MRI allows the diagnosis even in the absence of widespread dural sinus occlusion. Low dose heparin may be a therapeutic option in these cases. This is the first report of neonatal internal venous thrombosis due to hereditary lipoprotein (a) level elevation, which must be included in the list of possible predisposing conditions.