Microballoon pressure sensors for particle imaging manometry in liquid and gaseous media.

We present the fabrication and testing of engineered microballoon particles that expand and contract under external pressure changes hence serving as microscopic pressure sensors. The particles consist of 12 µm hollow flexible 0.4 µm-thick parylene-C shells with and without a coating of ultrathin Al2O3 diffusion barriers, and the changes in the particle radius are measured from the particle spectral reflectivity. The microballoons display radial pressure sensitivities of 0.64 nm psi(-1) and 0.44 nm psi(-1), respectively in agreement with theoretical estimates. The microballoon devices were used for mapping the internal pressure drop within microfluidic chips. These devices experience nearly spherical symmetry which could make them potential flow-through sensors for the augmentation of particle-based flow characterization methodologies extending today's capabilities of particle imaging velocimetry.

Molecular bridge-mediated ultralow-power gas sensing.

We report the electrical detection of captured gases through measurement of the quantum tunneling characteristics of gas-mediated molecular junctions formed across nanogaps. The gas-sensing nanogap device consists of a pair of vertically stacked gold electrodes separated by an insulating 6 nm spacer (~1.5 nm of sputtered α-Si and ~4.5 nm ALD SiO2), which is notched ~10 nm into the stack between the gold electrodes. The exposed gold surface is functionalized with a self-assembled monolayer (SAM) of conjugated thiol linker molecules. When the device is exposed to a target gas (1,5-diaminopentane), the SAM layer electrostatically captures the target gas molecules, forming a molecular bridge across the nanogap. The gas capture lowers the barrier potential for electron tunneling across the notched edge region, from ~5 eV to ~0.9 eV and establishes additional conducting paths for charge transport between the gold electrodes, leading to a substantial decrease in junction resistance. We demonstrated an output resistance change of >108 times upon exposure to 80 ppm diamine target gas as well as ultralow standby power consumption of <15 pW, confirming electron tunneling through molecular bridges for ultralow-power gas sensing.

Quantum Tunneling Hygrometer with Temperature Stabilized Nanometer Gap.

We present the design, fabrication and response of a humidity sensor based on electrical tunneling through temperature-stabilized nanometer gaps. The sensor consists of two stacked metal electrodes separated by ~2.5 nm of vertical air gap. Upper and lower electrodes rest on separate 1.5 µm thick polyimide patches with nearly identical thermal expansion but different gas absorption characteristics. When exposed to a humidity change, the patch under the bottom electrode swells but the patch under the top electrode does not, as it is covered with a water-vapor diffusion barrier ~8 nm of Al2O3. The air gap thus decreases leading to increase in the tunneling current across the junction. The gap however is independent of temperature fluctuations as both patches expand or contract by near equal amounts. Humidity sensor action demonstrates an unassisted reversible resistance reduction Rmax/Rmin ~105 when the device is exposed to 20-90 RH% at a standby DC power consumption of ~0.4 pW. The observed resistance change when subject to a temperature sweep of 25-60 ° C @24% RH was ~0.0025% of the full device output range.

An integrated nanoliter DNA analysis device.

A device was developed that uses microfabricated fluidic channels, heaters, temperature sensors, and fluorescence detectors to analyze nanoliter-size DNA samples. The device is capable of measuring aqueous reagent and DNA-containing solutions, mixing the solutions together, amplifying or digesting the DNA to form discrete products, and separating and detecting those products. No external lenses, heaters, or mechanical pumps are necessary for complete sample processing and analysis. Because all of the components are made using conventional photolithographic production techniques, they operate as a single closed system. The components have the potential for assembly into complex, low-power, integrated analysis systems at low unit cost. The availability of portable, reliable instruments may facilitate the use of DNA analysis in applications such as rapid medical diagnostics and point-of-use agricultural testing.

Generation of dynamic chemical signals with pulse code modulators.

The on-chip generation of dynamic chemical signals in a flow stream via pulse code modulation (PCM) is demonstrated. In this chip the output signal concentration is determined by dispersion and averaging of a serial stream of digitally encoded plugs of concentrated solute and pure solvent as the plugs flow through a long dispersive capillary. A two-bit PCM chemical signal generator was fabricated in two-level PDMS technology. The chip was capable of generating 31 distinct output levels with 10-plug cycles. Several example chemical waveforms (sawtooth and cosine) were generated at flow rates of 43.2 nL s(-1), and plug frequencies of up to 15 Hz, with maximum output signal bandwidth of up to about 1 Hz. The modulator chip was also used to synthesize physiological signals emulating intracellular beta-cell cytosolic Ca(2+) oscillations, extracellular beta-cell insulin release and rat-striatum dopamine release.

Fourier microfluidics.

We present a new experimental technique for the separation of dynamic chemical signals based on their frequency domain characteristics. Such a technique can be used to create filters that separate slow signals from fast signals from a common input flow stream. The propagation of time-varying chemical waves through networks of microfluidic channels is first examined. Mathematical models and a set of simple experiments are developed that demonstrate that short microfluidic channels behave as linear delay lines. The observed dispersive broadening and delay behavior can be explained in Fourier space in terms of corresponding phase delay, amplitude decay and characteristic transfer functions. Such delay components can be utilized to implement frequency dependent interference filters. An 8th order PDMS bandpass filter chip demonstrating these ideas was constructed. The filter chip has a central frequency of 0.17 Hz and a bandwith of 0.04 Hz at a flow rate of 4 microL h(-1).

Lightweight Smart Autofocusing Eyeglasses.

More than 100 million people in the United States of America alone suffer from age-related presbyopia caused by a loss of focal accommodation of the eye crystalline lens as the lens stiffens with age. The resulting accommodative error or lag produces blurred images of objects placed at different distances. Conventional fixed uniform or graded power eyeglasses cannot provide accommodation thus resulting in significant visual impairment. In this paper we will discuss the implementation of lightweight auto-focusing eyeglasses that augment the accommodative range thus partially or fully restoring normal vision function. The paper discusses some aspects of the construction of tunable power eyepieces and the implementation of accommodation correction algorithms.

Generation of dynamic chemical signals with microfluidic C-DACs.

The utilization of microfluidic "lab-on-a-chip" devices in fundamental medical research, drug discovery and clinical diagnostics has rapidly increased in the past decade. Lab-on-a-chip devices process small volumes of analytes and reagents through on-chip microfluidic signal processing circuits. This paper discusses the implementation of a basic microfluidic circuit block, the concentration digital-to-analog converter (or C-DAC) which produces discretized chemical concentrations in a constant stream of solvent. The chemical concentration is controlled by a time-varying digital word; hence C-DACs are suitable for on-chip generation of arbitrary chemical signals. A 4-bit continuous-flow C-DAC was fabricated in two-level PDMS technology and tested. Several chemical waveforms (sawtooth, cosine, and ramp) were generated at flow rates of 2 microL min(-1) and frequencies of 0.6-4 mHz. The frequency cut off of this C-DAC was approximately 500 mHz.

Short stature and body proportion in thalassaemia.

Short stature and short trunk have been reported in thalassaemic patients. We report a study on stature and body proportions in 476 patients (2-36 years old) with beta-thalassaemia major, followed in 12 Italian centres. Auxological data (standing height, sitting height, subischial leg length, target height), haematological data (age at first transfusion, age at start of desferrioxamine [DFX] chelation, mean dose of DFX, ferritin values) and information regarding the presence of endocrine disorders and of bone lesions, were collected and analysed according to the age of the patients, in order to investigate the natural history of the disproportion and the role of siderosis, DFX toxicity and endocrine disorders. Our data indicate that about 18% of thalassaemic patients exhibit short stature; disproportion between the upper and lower body segments is present in 14%; however, a short trunk despite normal stature is present in another 40% of patients. This is due to a spinal growth impairment which starts in infancy and progressively aggravates. We think that a short trunk is peculiar to the disease itself; however, other factors such as hypogonadism, siderosis, or DFX-induced bone dysplasia are probably involved in aggravating the body disproportion in these patients.

[Cephalometric evaluation of hyoid bone position in patients with obstructive sleep apnea]. / Valutazione cefalometrica della posizione dell'osso ioide in soggetti affetti da apnea ostruttiva notturna.

AIM: The aim of this study was to evaluate cephalometrically the relationship between hyoid bone position and obstructive sleep apnea (OSA). METHODS: Two groups were examined: the experimental Group (SG), composed of 15 OSA patients, and the Control Group (CG), composed of 15 healthy subjects. Both SG and CG patients were subjected to lateral teleradiography. On each radiography were effected cephalometric measurements to evaluate hyoid bone position and the results obtained were compared. RESULTS: From data comparison it turned out that, as already described in the literature, in OSA patients hyoid bone is, on average, in a lower and in a more posterior position than in control group patients. CONCLUSION: This altered hyoid bone position may influence tongue position and upper airway patency. All this makes it clear that cephalometric study is important for diagnosis and treatment of OSA patients.

[Thyroid function in the aged admitted to a nursing home]. / Función tiroidea en ancianos al ingreso en una residencia.

BACKGROUND: Intrinsic thyroid diseases and so-called sick euthyroid syndrome are frequent among the elderly. Therefore, we set out to assess the usefulness of the measurement of thyroid hormones and TSH on admission to a public nursing home. METHODS: A medical history, physical examination, geriatric assessment and a venous sample were taken from 201 elderly subjects on admission to a nursing home. Thyroid hormones and TSH were measured in all cases. All subjects were classified as valid, mentally impaired, or physically impaired, according to the Spanish Red Cross Scales. RESULTS: Sixty non-disabled and 141 disabled elders were studied. Sixteen (7.9%) cases of primary hypothyroidism were found, of whom 7 (3.5%) were deemed deserving treatment with L-thyroxine, their mean daily dose being 114.3 mcg. Sick euthyroid syndrome was considered to be present in 28 (13.9%) cases, of whom 25 had a normal T4, three had a low T4, and none had a high T4. No cases of hyperthyroidism were detected. Thyroid hormone abnormalities were not statistically associated with age, gender, or physical or mental disability. CONCLUSIONS: On admission to the nursing home, nearly 8% of the elders have hypothyroidism, and an additional 14% have the sick euthyroid syndrome. Routine measurement of T4 and TSH in elders on admission to a nursing home has a favorable cost-utility ratio.

[Anemia and functional incapacity at admission to a geriatric home]. / Anemia e incapacidad funcional al ingreso en una residencia geriátrica.

AIM: To ascertain the prevalence of anemia on admission to a nursing home, and to assess the relationship between the observed cases of anemia and the functional status of those subjects. METHODS: We studied 198 subjects: 82 men (41%) aged 75.8 +/- 8.8 years, and 116 women (59%) aged 78.2 +/- 8.3 years. Anemia was diagnosed according to the criteria of the World Health Organization. The classification as non-disabled, or physically or mentally disabled, was done according to the Scales of the Spanish Red Cross. RESULTS: Anemia was diagnosed in 36% of the males, being microcytic in 14%, normocytic in 83%, and macrocytic only in 3% of them. Among women there were 44% with anemia, which was microcytic in 16%, normocytic in 80%, and macrocytic in 4% of cases. The prevalence of anemia increased with age in both sexes. Among men, anemia was significantly associated (p = 0.013) with physical disability, whereas among women this association just fell off significance (p = 0.06). There was no association of anemia with mental disability. No association was found between serum concentrations of ferritin, vitamin B12, or folic acid, and the classification as non-disabled, or as physically or mentally disabled. CONCLUSIONS: Anemia is found in about 40% of the elderly on admission to our nursing home. Anemia is associated with older age and with physical disability, but not with mental disability. Whether anemia on admission entails a higher risk of disability onset during the stay in the nursing home remains to be elucidated.

A droplet-based novel approach for viable and low volume consumption surface plasmon resonance bio-sensing inside a polydimethylsiloxane microchip.

Over the course of last two decades, surface plasmon resonance (SPR) has emerged as a viable candidate for label-free detection and characterization for a large pool of biological interactions, ranging from hybridization of oligonucleotides to high throughput drug-screening. Conventional SPR bio-sensing involves a step-response method where the SPR sensorgram in response to a switched sequential flow of analyte and buffer is plotted in real-time and fitted to an exponential curve to extract the associative and dissociative reaction rates. Such measurement schemes involve continuous flow conditions where a substantial reagent volume is consumed and is subject to dispersive mixing at flow switching zones. In this paper, we demonstrate a new plug-train SPR technique in a microfluidic chip that separates and singulates solvent plugs in analyte and buffer by an immiscible air phase. Bio-samples are first discretized within plug droplets with volumes in order of few hundred nanoliters or less followed by pressure-driven transport onto SPR sensing sites of this hydrophobically modified SPR microdevise. The kinetic constants ka and kd for a model protein-small molecule interaction pair are extracted from a plug-train signal and are shown to be in reasonable agreement with our previous reports.

Probing protein binding spectra with Fourier microfluidics.

New developments in microfluidic chip technology enable the construction of chemical spectrum analyzers that can probe the binding interactions between chemical entities. In this paper we report the implementation of a microfluidic chip suitable for Fourier transform measurements of biochemical interactions. The chip consists of a chemical signal generator, a flow cell and a binding sensor surface. The microfluidic signal generator produces a periodic stream of protein plugs in solution flowing at constant velocity through the cell. This flow produces periodic association and dissociation cycles of the protein to a functionalized gold sensing surface placed inside the cell. The sensor activity corresponding to the phasor response of the chemical interaction at the excitation frequency is measured optically using surface plasmon resonance (SPR) imaging. We demonstrated the feasibility of the technique using a model system of carbonic anhydrase-II (CA-II) and immobilized 4-(2-Aminoethyl) benzenesulfonamide (ABS) ligand. The observed transfer function showed a dominant pole at 10.2 mHz corresponding to association and dissociation constants of 4.8 × 10(3) M(-1)·s(-1), and 3.5 × 10(-2) s(-1) respectively.

A combinatorial multicomponent plug mixer for systems chemistry.

We report the construction and testing of a combinatorial multicomponent plug mixer (CMPM) chip that generates a large number of mix ratios. The CMPM chip has been designed to study ribonucleotide reductase (RNR) protein-protein/protein-ligand interaction networks. The 4-component chip is capable of 5400 different combinations in a 30 plug cycle. CMPM chips were tested producing fluorescent dye and dihydrofolate reductase NADPH/MX mixtures with plug lengths of 2 mm.

Microfabricated incandescent lamps.

A silicon filament vacuum sealed incandescent light source has been fabricated using IC technology. The incandescent source consists of a heavily doped p(+) polysilicon filament coated with silicon nitride and enclosed in a vacuum sealed ( approximately 80-mT) cavity in the silicon chip surface. The filament is electrically heated to reach incandescence at a temperature near 1400 K. The power required to achieve this temperature for a filament 510 x 5 x 1 microm(3) is 5 mW yielding a total optical power of 250 microW with a peak distribution wavelength near 2.5 microm. The radiation emitted by this source approximately follows Lambert's cosine law. The energy conversion efficiency is 5%.

Nanoliter liquid metering in microchannels using hydrophobic patterns.

Nanoliter-sized liquid drops can be accurately metered inside hydrophilic microchannels using a combination of hydrophobic surface treatment and air pressure. The technique involves spontaneously filling the microchannels up to a hydrophobic region and splitting a liquid drop by injecting air through a hydrophobic side channel. The hydrophobic regions are fabricated by using a patterned metal mask on a substrate. The patterned substrate is immersed in an isooctane solution containing 1H,1H,2H,2H-per-fluorodecyltrichlorosilane to form hydrophobic patches on the exposed surface. Stripping the metal mask leaves the hydrophobic patches and restores the hydrophilic substrate surface. Precise and accurate liquid volumes, ranging from 0.5 to 125 nanoliters, have been metered using this technique. Theoretical predictions of the pressure needed to meter drops compare well with the experimental values.