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Biomedical subjects

Andreas Hierlemann

Publications and source records attributed to Andreas Hierlemann.

11 recordsLinked to original sources
PubMed2006

Detection and discrimination capabilities of a multitransducer single-chip gas sensor system.

The performance of a single-chip, three-transducer, complementary metal oxide semiconductor gas sensor microsystem has been thoroughly evaluated. The monolithic gas sensor system includes three polymer-coated transducers, a mass-sensitive cantilever, a thermoelectric calorimetric sensor, and an interdigitated capacitive sensor that are integrated along with all electronic circuits needed to operate these sensors. The system additionally includes a temperature sensor and a serial interface unit so that it can be directly connected to, for example, a microcontroller. Several multitransducer chips have been coated with various partially selective polymers and then have been exposed to different volatile organic compounds. The sensitivities of the three different polymer-coated transducers to defined sets of gaseous analytes have been determined. The obtained sensitivity values have then been normalized with regard to the partition coefficients of the respective analyte/polymer combination to reveal the transducer-specific effects. The results of this investigation show that the three different transducers respond to fundamentally different molecular properties, such as the analyte molecular mass (mass-sensitive), its dielectric coefficient (capacitive), and its sorption heat (calorimetric) so that correlations between the determined sensitivity values and the different molecular properties of the absorbed analytes could be established. The information as provided by the system, hence, represents a body of orthogonal data that can serve as input to appropriate signal processing and pattern recognition techniques to address issues such as the quantification of analytes in mixtures.

Journal Article↗
PubMed2006

Characterization of a microfluidic dispensing system for localised stimulation of cellular networks.

We present a 3-D microfluidic device designed for localized drug delivery to cellular networks. The device features a flow cell comprising a main channel for nutrient delivery as well as multiple channels for drug delivery. This device is one key component of a larger, fully integrated system now under development, based upon a microelectrode array (MEA) with on-chip CMOS circuitry for recording and stimulation of electrogenic cells (e.g. neurons, cardiomyocytes). As a critical system unit, the microfluidics must be carefully designed and characterized to ensure that candidate drugs are delivered to specific regions of the culture at known concentrations. Furthermore, microfluidic design and functionality is dictated by the size, geometry, and material/electrical characteristics of the CMOS MEA. Therefore, this paper reports on the design considerations and fabrication of the flow cell, including theoretical and experimental analysis of the mass transfer properties of the nutrient and drug flows, which are in good agreement with one another. To demonstrate proof of concept, the flow cell was mounted on a dummy CMOS chip, which had been plated with HL-1 cardiomyocytes. A test chemical compound was delivered to the cell culture in a spatially resolved manner. Envisioned applications of this stand-alone system include simultaneous toxicological testing of multiple compounds and chemical stimulation of natural neural networks for neuroscience investigations.

Algorithms↗
PubMed2006

Transient signal analysis using complementary metal oxide semiconductor capacitive chemical microsensors.

This work explores the possibility to discriminate analytes based on their nonequilibrium signals in polymer-coated capacitive chemical microsensors. The analyte uptake in the chemically sensitive polymer layers of 3-7-microm thickness has been analyzed using a diffusion model and the dynamic sensor response data. The shapes of the response profiles have been calculated analytically. Despite the simplifications in the model, the observed transient signal profiles could be described accurately. Comparison of the measured diffusion coefficients (on the order of 10(-12) m2/s) with literature values measured at similar concentration levels showed good agreement. Concentration-independent diffusion coefficients for several analyte/polymer combinations (poly(etherurethane)/all analytes; poly(epichlorohydrin)/alcohols) as well as slightly concentration-dependent diffusion coefficients (poly(epichlorohydrin)/toluene or ethyl cellulose/toluene) have been found in the investigated concentration range of tens to hundreds of pascals gas-phase partial pressure. The diffusion times of water and the first aliphatic monohydric alcohols in the polymers are strongly correlated to their molecular size. The discrimination of these substances based on dynamic sensor data of a single sensor could be demonstrated. In particular, the analysis of mixtures of analytes with similar chemical behavior (water/ethanol or methanol/ethanol) by means of analyzing the response profile of single-exposure steps or by applying a series of decreasingly long alternating target gas exposure and carrier gas exposure steps has been performed.

Journal Article↗
PubMed2006

Microfluidics/CMOS orthogonal capabilities for cell biology.

The study of individual cells and cellular networks can greatly benefit from the capabilities of microfabricated devices for the stimulation and the recording of electrical cellular events. In this contribution, we describe the development of a device, which combines capabilities for both electrical and pharmacological cell stimulation, and the subsequent recording of electrical cellular activity. The device combines the unique advantages of integrated circuitry (CMOS technology) for signal processing and microfluidics for drug delivery. Both techniques are ideally suited to study electrogenic mammalian cells, because feature sizes are of the same order as the cell diameter, approximately 50 microm. Despite these attractive features, we observe a size mismatch between microfluidic devices, with bulky fluidic connections to the outside world, and highly miniaturized CMOS chips. To overcome this problem, we developed a microfluidic flow cell that accommodates a small CMOS chip. We simulated the performances of a flow cell based on a 3-D microfluidic system, and then fabricated the device to experimentally verify the nutrient delivery and localized drug delivery performance. The flow-cell has a constant nutrient flow, and six drug inlets that can individually deliver a drug to the cells. The experimental analysis of the nutrient and drug flow mass transfer properties in the flowcell are in good agreement with our simulations. For an experimental proof-of-principle, we successfully delivered, in a spatially resolved manner, a 'drug' to a culture of HL-1 cardiac myocytes.

Cell Culture Techniques↗
PubMed2006

Tissue-transplant fusion and vascularization of myocardial microtissues and macrotissues implanted into chicken embryos and rats.

Cell-based therapies and tissue engineering initiatives are gathering clinical momentum for next-generation treatment of tissue deficiencies. By using gravity-enforced self-assembly of monodispersed primary cells, we have produced adult and neonatal rat cardiomyocyte-based myocardial microtissues that could optionally be vascularized following coating with human umbilical vein endothelial cells (HUVECs). Within myocardial microtissues, individual cardiomyocytes showed native-like cell shape and structure, and established electrochemical coupling via intercalated disks. This resulted in the coordinated beating of microtissues, which was recorded by means of a multi-electrode complementary metal-oxide-semiconductor microchip. Myocardial microtissues (microm3 scale), coated with HUVECs and cast in a custom-shaped agarose mold, assembled to coherent macrotissues (mm3 scale), characterized by an extensive capillary network with typical vessel ultrastructures. Following implantation into chicken embryos, myocardial microtissues recruited the embryo's capillaries to functionally vascularize the rat-derived tissue implant. Similarly, transplantation of rat myocardial microtissues into the pericardium of adult rats resulted in time-dependent integration of myocardial microtissues and co-alignment of implanted and host cardiomyocytes within 7 days. Myocardial microtissues and custom-shaped macrotissues produced by cellular self-assembly exemplify the potential of artificial tissue implants for regenerative medicine.

Animals↗
PubMed2005

Impedance characterization and modeling of electrodes for biomedical applications.

A low electrode-electrolyte impedance interface is critical in the design of electrodes for biomedical applications. To design low-impedance interfaces a complete understanding of the physical processes contributing to the impedance is required. In this work a model describing these physical processes is validated and extended to quantify the effect of organic coatings and incubation time. Electrochemical impedance spectroscopy has been used to electrically characterize the interface for various electrode materials: platinum, platinum black, and titanium nitride; and varying electrode sizes: 1 cm2, and 900 microm2. An equivalent circuit model comprising an interface capacitance, shunted by a charge transfer resistance, in series with the solution resistance has been fitted to the experimental results. Theoretical equations have been used to calculate the interface capacitance impedance and the solution resistance, yielding results that correspond well with the fitted parameter values, thereby confirming the validity of the equations. The effect of incubation time, and two organic cell-adhesion promoting coatings, poly-L-lysine and laminin, on the interface impedance has been quantified using the model. This demonstrates the benefits of using this model in developing better understanding of the physical processes occurring at the interface in more complex, biomedically relevant situations.

Biomedical Engineering↗
PubMed2004

Single-chip mechatronic microsystem for surface imaging and force response studies.

We report on a stand-alone single-chip (7 x 10 mm) atomic force microscopy unit including a fully integrated array of cantilevers, each of which has an individual actuation, detection, and control unit so that standard atomic force microscopy operations can be performed by means of the chip only without any external controller. The system offers drastically reduced overall size and costs as well as increased scanning speed and can be fabricated with standard complementary metal oxide semiconductor technology with some subsequent micromachining steps to form the cantilevers. Full integration of microelectronic and micromechanical components on the same chip allows for the controlling and monitoring of all system functions. The on-chip circuitry, which includes analog signal amplification and filtering stages with offset compensation, analog-to-digital converters, a powerful digital signal processor, and an on-chip digital interface for data transmission, notably improves the overall system performance. The microsystem characterization evidenced a vertical resolution of < 1 nm and a force resolution of < 1 nN as shown in the measurement results. The monolithic system represents a paradigm of a mechatronic microsystem that allows for precise and fully controlled mechanical manipulation in the nanoworld.

Journal Article↗
PubMed2004

Metal oxide-based monolithic complementary metal oxide semiconductor gas sensor microsystem.

A fully integrated gas sensor microsystem is presented, which comprises for the first time a micro hot plate as well as advanced analog and digital circuitry on a single chip. The micro hot plate is coated with a nanocrystalline SnO2 thick film. The sensor chip is produced in an industrial 0.8-microm CMOS process with subsequent micromachining steps. A novel circular micro hot plate, which is 500 x 500 microm(2) in size, features an excellent temperature homogeneity of +/-2% over the heated area (300-microm diameter) and a high thermal efficiency of 6.0 degrees C/mW. A robust prototype package was developed, which relies on standard microelectronic packaging methods. Apart from a microcontroller board for managing chip communication and providing power supply and reference signals, no additional measurement equipment is needed. The on-chip digital temperature controller can accurately adjust the membrane temperature between 170 and 300 degrees C with an error of +/-2 degrees C. The on-chip logarithmic converter covers a wide measurement range between 1 kOmega and 10 MOmega. CO concentrations in the sub-parts-per-million range are detectable, and a resolution of +/-0.1 ppm CO was achieved, which renders the sensor capable of measuring CO concentrations at threshold levels.

Journal Article↗
PubMed2004

Tuning sensitivity and selectivity of complementary metal oxide semiconductor-based capacitive chemical microsensors.

New details on selectivity and sensitivity of fully integrated CMOS-based capacitive chemical microsensor systems are revealed. These microsystems have been developed to detect volatile organics in ambient air and rely on polymeric sensitive layers. The sensitivity and selectivity changes induced by thickness variation of the sensitive polymer layer allow for tuning of the layer parameters to achieve desired sensor features. Cross-sensitivity to interfering agents can be drastically reduced, as is shown for two important cases: (a). rendering the capacitive sensor insensitive to a low-dielectric-constant analyte (lower than that of the polymer) and (b). reducing the influence of a high-dielectric-constant analyte, such as water, on the sensor response. The second case is of vital importance for capacitive sensors, since water is omnipresent and evokes large capacitive sensor signals. The thickness-induced selectivity is explained as a combination of dielectric constant change and swelling and has been confirmed by measurements. Experimentally determined sensitivities qualitatively and quantitatively coincide with the calculated values implying understanding of the sensing mechanism.

Absorption↗
PubMed2002

Complementary metal oxide semiconductor cantilever arrays on a single chip: mass-sensitive detection of volatile organic compounds.

The sensing behavior of polymer-coated resonant cantilevers for mass-sensitive detection of volatile organic compounds was investigated. Industrial complementary metal oxide semiconductor (CMOS) technology combined with subsequent CMOS-compatible micromachining was used to fabricate a single-chip system comprising the transducers and all necessary driving and signal-conditioning circuitry. An analytical model was developed to describe the mass-sensing mechanism of polymer-coated resonant cantilevers. The model was validated by measurements of various gaseous analytes. As an exemplary application, the quantitative analysis of a binary mixture using an array of four cantilevers is described. Experimental results are given for the concentration prediction of a mixture of n-octane and toluene. Finally, it was established that the limit of detection achieved with cantilever sensors is comparable to that of other acoustic wave-based gas sensors.

Journal Article↗