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  • 1.
    Bass, Tarek
    KTH, School of Biotechnology (BIO), Protein Technology.
    Affibody molecules targeting HER3 for cancer therapy2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The development of targeted therapy has contributed tremendously to the treatment of patients with cancer. The use of highly specific affinity proteins to target cancer cells has become a standard in treatment strategies for several different cancers. In light of this, many cancer cell markers are investigated for their potential use in diagnostics and therapy. One such marker is the human epidermal growth factor receptor 3, HER3. It has been established as an important contributor to many cancer types. The function of HER3 is to relay cell growth signals from outside of the cell to the inside. Interfering with- and inhibit- ing the function of HER3 has emerged as an interesting strategy for cancer therapeutics. The studies presented in this thesis aim to target HER3 with small, engineered affinity domain proteins for therapeutic purposes. Monomeric affibody molecules have previously been engineered to bind and inhibit HER3 in vitro. Due to the relatively low expression of HER3, an increase in valency appears promising to strengthen the therapeutic potential. Affibody molecules targeting the receptor were thus linked to form bivalent and bispecific constructs and evaluated both in vitro and in vivo. In the first study of this thesis affibody molecules specific for HER3 and HER2 were fused to an albumin binding domain to form bivalent and bispecific construct. The constructs inhibited ligand-induced receptor phos- phorylation of both HER2 and HER3 more efficiently than monomeric affibody molecules. A second approach to enhance the potential of affibody molecules in tumor targeting is described in the second study, where monomeric HER3-binding affibody molecules were engineered to increase their affinity for HER3. The resulting variants showed a 20-fold in- creased affinity and higher capacity to inhibit cancer cell growth. Combining the findings of the first two studies, the third study describes the evaluation of a HER3-targeting bivalent affibody construct for potential application as a therapeutic. Here, the bivalent construct inhibited cancer cell growth in vitro and was found to slow down tumor growth in mice, while being well tolerated and showing no visible toxicity. The fourth study built upon these findings and compares a very similar bivalent construct to the clinically-investigated HER3-specific monoclonal antibody seribantumab. The affibody construct showed very comparable efficacy with the antibody in terms of decreasing tumor growth rate and ex- tending mouse survival. Collectively, these works describe for the first time the use of alternative affinity protein constructs with therapeutic potential targeting HER3.

  • 2.
    Bass, Tarek
    KTH, School of Biotechnology (BIO), Protein Technology.
    Evaluating the therapeutic potential of a dimeric HER3-binding affibody construct in comparison with a monoclonal antibody, seribantumab.Manuscript (preprint) (Other academic)
    Abstract [en]

    A number of monoclonal antibodies targeting HER3 are currently under clinical investigation as potential cancer therapeutics. We have earlier generated high affinity (low picomolar) affibody molecules targeting HER3. These are small, 58 amino acid, non-immunoglobulin based scaffold proteins that have proved suitable for tumor targeting applications, previously primarily for molecular imaging purposes. Our high affinity HER3-binding affibody molecule has demonstrated to have anti-proliferative capacity on HER3-positive tumor cells. When formatted as a bivalent construct, in which the two affibody moieties are flanking a small albumin-binding domain (ABD), we have recently demonstrated that tumor growth could be delayed in mice for HER3-positive xenografts. In this study, we have modified the construct further and reduced the size. In a comparative study, we evaluated safety, the capacity to delay tumor growth in mice with BxPC-3 xenografts, and mouse survival. Our novel construct was compared to the HER3-specific monoclonal antibody seribantumab (MM-121), presently in clinical development. They were found to be equally potent in their therapeutic effects and in their safety profile. We conclude that this format of bivalent HER3-binding affibody molecules seems promising for further evaluation as candidate therapeutics for treatment of HER3-overexpressing tumors.

  • 3. Bello, M. A.
    et al.
    Ruiz-León, Y.
    Sandoval-Sierra, J. V.
    Rezinciuc, Svetlana
    KTH, School of Biotechnology (BIO), Glycoscience.
    Diéguez-Uribeondo, J.
    Scanning electron microscopy (SEM) protocols for problematic plant, oomycete, and fungal samples2017In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, Vol. 2017, no 120, article id e55031Article in journal (Refereed)
    Abstract [en]

    Common problems in the processing of biological samples for observations with the scanning electron microscope (SEM) include cell collapse, treatment of samples from wet microenvironments and cell destruction. Using young floral tissues, oomycete cysts, and fungi spores (Agaricalesas examples, specific protocols to process delicate samples are described here that overcome some of the main challenges in sample treatment for image capture under the SEM. Floral meristems fixed with FAA (Formalin-Acetic-Alcohol) and processed with the Critical Point Dryer (CPD) did not display collapsed cellular walls or distorted organs. These results are crucial for the reconstruction of floral development. A similar CPD-based treatment of samples from wet microenvironments, such as the glutaraldehyde-fixed oomycete cysts, is optimal to test the differential growth of diagnostic characteristics (e.g., the cyst spines) on different types of substrates. Destruction of nurse cells attached to fungi spores was avoided after rehydration, dehydration, and the CPD treatment, an important step for further functional studies of these cells. The protocols detailed here represent low-cost and rapid alternatives for the acquisition of good-quality images to reconstruct growth processes and to study diagnostic characteristics.

  • 4. Bengtsson, Erik
    et al.
    Nerjovaj, Pashtrik
    Wangefjord, Sakarias
    Nodin, Björn
    Eberhard, Jakob
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Borgquist, Signe
    Jirström, Karin
    HMG-CoA reductase expression in primary colorectal cancer correlates with favourable clinicopathological characteristics and an improved clinical outcome2014In: Diagnostic Pathology, ISSN 1746-1596, E-ISSN 1746-1596, Vol. 9, no 1, p. 78-Article in journal (Refereed)
    Abstract [en]

    Background: An association between tumor-specific HMG-CoA reductase (HMGCR) expression and good prognosis has previously been demonstrated in breast and ovarian cancer. In this study, the expression, clinicopathological correlates and prognostic value of HMGCR expression in colorectal cancer was examined. Findings: Immunohistochemical expression of HMGCR was assessed in tissue microarrays with primary tumours from 557 incident cases of colorectal cancer in the Malmo Diet and Cancer Study. Pearson's Chi Square test was applied to explore the associations between HMGCR expression and clinicopathological factors and other investigative biomarkers. Kaplan Meier analysis and Cox proportional hazards modeling were used to assess the relationship between HMGCR expression and cancer-specific survival (CSS) according to negative vs positive HMGCR expression. A total number of 535 (96.0%) tumours were suitable for analysis, of which 61 (11.4%) were HMGCR negative. Positive cytoplasmic HMGCR expression was associated with distant metastasis-free disease at diagnosis (p = 0.002), lack of vascular invasion (p = 0.043), microsatellite-instability (p = 0.033), expression of cyclin D1 (p = <0.001) and p21 (p = <0.001). Positive HMGCR expression was significantly associated with a prolonged CSS in unadjusted Cox regression analysis in the entire cohort (HR = 1.79; 95% CI 1.20-2.66) and in Stage III-IV disease (HR = 1.71; 95% CI 1.09-2.68), but not after adjustment for established clinicopathological parameters. Conclusions: Findings from this prospective cohort study demonstrate that HMGCR is differentially expressed in colorectal cancer and that positive expression is associated with favourable tumour characteristics and a prolonged survival in unadjusted analysis. The utility of HMGCR as a predictor of response to neoadjuvant or adjuvant statin treatment in colorectal cancer merits further study. Virtual slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2115647072103464.

  • 5. Brazalez, Astrid Algaba
    et al.
    Manholm, Lars
    Johansson, Martin
    Quevedo-Teruel, Oscar
    Miao, Jingwei
    KTH, School of Electrical Engineering and Computer Science (EECS), Electromagnetic Engineering.
    Investigation of a Ka-band Luneburg Lens Made of a Glide-Symmetric Holey Structure2017In: 2017 INTERNATIONAL SYMPOSIUM ON ANTENNAS AND PROPAGATION (ISAP 2017), IEEE , 2017Conference paper (Refereed)
    Abstract [en]

    A Ka-hand 2D flat-profiled Luneburg lens antenna implemented with a glide-symmetric holey structure is presented. The required refractive index for the lens design has been investigated via an analysis of the hole depth and the gap between the two metallic layers constituting the lens. The final unit cell is described and applied to create the complete metasurface Luneburg lens showing that a plane wave is obtained when feeding at an opposite arbitrary point with a discrete source.

  • 6.
    Hasmats, Johanna
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Analysis of genetic variations in cancer2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this thesis is to apply recently developed technologies for genomic variation analyses, and to ensure quality of the generated information for use in preclinical cancer research.

    Faster access to a patients’ full genomic sequence for a lower cost makes it possible for end users such as clinicians and physicians to gain a more complete understanding of the disease status of a patient and adjust treatment accordingly. Correct biological interpretation is important in this context, and can only be provided through fast and simple access to relevant high quality data.

    Therefore, we here propose and validate new bioinformatic strategies for biomarker selection for prediction of response to cancer therapy. We initially explored the use of bioinformatic tools to select interesting targets for toxicity in carboplatin and paclitaxel on a smaller scale. From our findings we then further extended the analysis to the entire exome to look for biomarkers as targets for adverse effects from carboplatin and gemcitabine. To investigate any bias introduced by the methods used for targeting the exome, we analyzed the mutation profiles in cancer patients by comparing whole genome amplified DNA to unamplified DNA. In addition, we applied RNA-seq to the same patients to further validate the variations obtained by sequencing of DNA. The understanding of the human cancer genome is growing rapidly, thanks to methodological development of analysis tools. The next step is to implement these tools as a part of a chain from diagnosis of patients to genomic research to personalized treatment.

  • 7.
    Juntikka, Rickard
    et al.
    KTH, School of Engineering Sciences (SCI), Aeronautical and Vehicle Engineering, Lightweight Structures.
    Kleiven, Svein
    KTH, School of Technology and Health (STH), Neuronic Engineering (Closed 20130701).
    Hallström, Stefan
    KTH, School of Engineering Sciences (SCI), Aeronautical and Vehicle Engineering, Lightweight Structures.
    Optimization of single skin surfaces for head injury prevention - a comparison of optima calculated for global versus local injury thresholds2004In: International Journal of Crashworthiness, ISSN 1358-8265, E-ISSN 1754-2111, Vol. 9, no 4, p. 365-379Article in journal (Refereed)
    Abstract [en]

    This paper describes optimizations of material properties for a bonnet-like plate using finite element calculations and the Euro-NCAP pedestrian head impact test. Four different head models were used for the impact simulations, a Euro-NCAP dummy head, a Hybrid III dummy head and two biomechanical head models exhibiting different mechanical properties for the brain tissue. The objective function was to minimize the displacement of the bonnet plate while satisfying constraints on the head injury criterion (HIC), the resultant contact force and, for the human head models, the strain in the brain tissue. An investigation was also conducted of the kinematics of the head models during impact, evaluating the energy distribution and the apparent mass. The analysis gave at hand that optimization of the plate with respect to impact with the Euro-NCAP and Hybrid III head models reached substantially, different results compared to impact with the biomechanical head models. For the latter case, the stiffness of the brain tissue influenced which constraints were active in the final solution. The investigation of the kinematics at impact showed that a substantial portion of energy was confined within the brain during impact for the biomechanical head models. The apparent mass at impact coincided with the actual mass for the rigid dummy heads while for the human head models it was roughly the mass of the skull only.

  • 8. Katchy, Anne
    et al.
    Williams, Cecilia
    Profiling of estrogen-regulated microRNAs in breast cancer cells.2014In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, no 84, article id e51285Article in journal (Refereed)
    Abstract [en]

    Estrogen plays vital roles in mammary gland development and breast cancer progression. It mediates its function by binding to and activating the estrogen receptors (ERs), ERα, and ERβ. ERα is frequently upregulated in breast cancer and drives the proliferation of breast cancer cells. The ERs function as transcription factors and regulate gene expression. Whereas ERα's regulation of protein-coding genes is well established, its regulation of noncoding microRNA (miRNA) is less explored. miRNAs play a major role in the post-transcriptional regulation of genes, inhibiting their translation or degrading their mRNA. miRNAs can function as oncogenes or tumor suppressors and are also promising biomarkers. Among the miRNA assays available, microarray and quantitative real-time polymerase chain reaction (qPCR) have been extensively used to detect and quantify miRNA levels. To identify miRNAs regulated by estrogen signaling in breast cancer, their expression in ERα-positive breast cancer cell lines were compared before and after estrogen-activation using both the µParaflo-microfluidic microarrays and Dual Labeled Probes-low density arrays. Results were validated using specific qPCR assays, applying both Cyanine dye-based and Dual Labeled Probes-based chemistry. Furthermore, a time-point assay was used to identify regulations over time. Advantages of the miRNA assay approach used in this study is that it enables a fast screening of mature miRNA regulations in numerous samples, even with limited sample amounts. The layout, including the specific conditions for cell culture and estrogen treatment, biological and technical replicates, and large-scale screening followed by in-depth confirmations using separate techniques, ensures a robust detection of miRNA regulations, and eliminates false positives and other artifacts. However, mutated or unknown miRNAs, or regulations at the primary and precursor transcript level, will not be detected. The method presented here represents a thorough investigation of estrogen-mediated miRNA regulation.

  • 9.
    Khorshidi, Mohammad Ali
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Live Single Cell Imaging and Analysis Using Microfluidic Devices2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Today many cell biological techniques study large cell populations where an average estimate of individual cells’ behavior is observed. On the other hand, single cell analysis is required for studying functional heterogeneities between cells within populations. This thesis presents work that combines the use of microfluidic devices, optical microscopy and automated image analysis to design various cell biological assays with single cell resolution including cell proliferation, clonal expansion, cell migration, cell-cell interaction and cell viability tracking. In fact, automated high throughput single cell techniques enable new studies in cell biology which are not possible with conventional techniques.

    In order to automatically track dynamic behavior of single cells, we developed a microwell based device as well as a droplet microfluidic platform. These high throughput microfluidic assays allow automated time-lapse imaging of encapsulated single cells in micro droplets or confined cells inside microwells. Algorithms for automatic quantification of cells in individual microwells and micro droplets are developed and used for the analysis of cell viability and clonal expansion. The automatic counting protocols include several image analysis steps, e.g. segmentation, feature extraction and classification. The automatic quantification results were evaluated by comparing with manual counting and revealed a high success rate. In combination these automatic cell counting protocols and our microfluidic platforms can provide statistical information to better understand behavior of cells at the individual level under various conditions or treatments in vitro exemplified by the analysis of function and regulation of immune cells. Thus, together these tools can be used for developing new cellular imaging assays with resolution at the single cell level.

    To automatically characterize transient migration behavior of natural killer (NK) cells compartmentalized in microwells, we developed a method for single cell tracking. Time-lapse imaging showed that the NK cells often exhibited periods of high motility, interrupted with periods of slow migration or complete arrest. These transient migration arrest periods (TMAPs) often overlapped with periods of conjugations between NK cells and target cells. Such conjugation periods sometimes led to cell-mediated killing of target cells. Analysis of cytotoxic response of NK cells revealed that a small sub-class of NK cells called serial killers was able to kill several target cells. In order to determine a starting time point for cell-cell interaction, a novel technique based on ultrasound was developed to aggregate NK and target cells into the center of the microwells. Therefore, these assays can be used to automatically and rapidly assess functional and migration behavior of cells to detect differences between health and disease or the influence of drugs.

    The work presented in this thesis gives good examples of how microfluidic devices combined with automated imaging and image analysis can be helpful to address cell biological questions where single cell resolution is necessary. 

  • 10.
    Mavajian, Zahra
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Investigation of DNA Base Excision Repair in MTH1 Depleted T-cell Acute Lymphoblastic Leukemia cells2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Genomic alterations may initiate cancer development as the consequence of endogenous or exogenous DNA damaging factors. Defects in DNA repair mechanisms may also facilitate cancer progression as well as accumulation of mutations which favor cancer cell survival. However, DNA repair pathways in cancer cells can be considered as their Achilles heel which are possible targets in order to compromise their survival. For instance, it has been demonstrated recently that inhibition of a protein called MTH1 via RNA interference (RNAi) or chemical inhibitors can stop tumor growth and triggers cell death by increasing the load of oxidative DNA damage. MTH1 is a hydrolase which converts 8-oxo-dGTP into 8-oxo-dGMP in order to prevent incorporation of oxidatively damaged nucleotides into DNA. In addition, DNA glycosylases which recognize and remove mismatched or damaged nucleotide pairs in DNA can also participate in repair of 8-oxo-dG, such as MUTYH repairing A:8-oxo-dG pair. The goal of the current study was to investigate the importance of MUTYH activity upon MTH1 depletion. The current study tried to answer whether simultaneous knock-down of MTH1 and MUTYH sensitizes cancer cells to oxidative stress and increases cell death. Both enzymes were simultaneously depleted in T cell acute lymphoblastic leukemia cells using RNAi. Then, we analyzed the efficiency of gene and protein knock-down by quantitative real-time-PCR and western blotting, respectively. Induction of cell death was also assessed by flow cytometric analysis of cell cycle. Afterwards, the effect of the treatments on DNA repair pathways was studied by analysis of gene expression of several DNA glycosylases and DNA polymerases using qRT-PCR. The results showed that concurrent depletion of both enzymes led to synergistic induction of cell death. Down-regulation of NEIL1 DNA glycosylase as well as POLQ and POLH DNA polymerases mRNAs adapted their DNA repair pathways to cope with induced damages under these conditions. Finally, the results of this study suggest that dual suppression of MTH1 and MUTYH may provide a new approach to reduce survival of T cell ALL.

  • 11.
    Nilsonne, Åsa
    et al.
    Karolinska Institutet.
    Sundberg, Johan
    KTH, Superseded Departments (pre-2005), Speech Transmission and Music Acoustics.
    Ternström, Sten
    KTH, Superseded Departments (pre-2005), Speech Transmission and Music Acoustics.
    Askenfelt, Anders
    KTH, Superseded Departments (pre-2005), Speech Transmission and Music Acoustics.
    Measuring the rate of change of voice fundamental frequency in fluent speech during mental depression1988In: The Journal of the Acoustical Society of America, Vol. 83, no 2, p. 716-728Article in journal (Refereed)
    Abstract [en]

    A method of measuring the rate of change of fundamental frequency has been developed in an effort to find acoustic voice parameters that could be useful in psychiatric research. A minicomputer program was used to extract seven parameters from the fundamental frequency contour of tape‐recorded speech samples: (1) the average rate of change of the fundamental frequency and (2) its standard deviation, (3) the absolute rate of fundamental frequency change, (4) the total reading time, (5) the percent pause time of the total reading time, (6) the mean, and (7) the standard deviation of the fundamental frequency distribution. The method is demonstrated on (a) a material consisting of synthetic speech and (b) voice recordings of depressed patients who were examined during depression and after improvement.

  • 12.
    Pardon, Gaspard
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Ladhani, Laila
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Sandström, Niklas
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Ettori, Maxime
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Lobov, Gleb
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Aerosol sampling using an electrostatic precipitator integrated with a microfluidic interface2015In: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 212, p. 344-352Article in journal (Refereed)
    Abstract [en]

    In this work, the development of a point-of-care (PoC) system to capture aerosol from litres of air directly onto a microfluidic lab-on-chip for subsequent analysis is addressed. The system involves an electrostatic precipitator that uses corona charging and electrophoretic transport to capture aerosol droplets onto a microfluidic air-to-liquid interface for downstream analysis. A theoretical study of the governing geometric and operational parameters for optimal electrostatic precipitation is presented. The fabrication of an electrostatic precipitator prototype and its experimental validation using a laboratory-generated aerosolized dye is described. Collection efficiencies were comparable to those of a state-of-the-art Biosampler impinger, with the significant advantage of providing samples that are at least 10 times more concentrated. Finally, we discuss the potential of such a system for breath-based diagnostics.

  • 13. Ravichandran, R.
    et al.
    Åstrand, Carolina
    KTH, School of Biotechnology (BIO), Industrial Biotechnology.
    Patra, H. K.
    Turner, Anthony P. F.
    Chotteau, Véronique
    KTH, School of Biotechnology (BIO), Industrial Biotechnology.
    Phopase, J.
    Intelligent ECM mimetic injectable scaffolds based on functional collagen building blocks for tissue engineering and biomedical applications2017In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 7, no 34, p. 21068-21078Article in journal (Refereed)
    Abstract [en]

    Hydrogels comprising natural extracellular matrix (ECM) components are very attractive as scaffolds for regenerative medicine applications due to their inherent biointeractive properties. Responsive materials that adapt to their surrounding environments and regulate transport of ions and bioactive molecules manifest significant advantages for biomedical applications. Although there are many exciting challenges, the opportunity to design, fabricate and engineer stimuli-responsive polymeric systems based on ECM components is particularly attractive for regenerative medicine. Here we describe a one-pot approach to fabricate in situ fast gellable intelligent ECM mimetic scaffolds, based on methacrylated collagen building blocks with mechanical properties that can be modulated in the kPa-MPa range and that are suitable for both soft and hard tissues. Physiochemical characterizations demonstrate their temperature and pH responsiveness, together with the structural and enzymatic resistance that make them suitable scaffolds for long-term use in regenerative medicine and biomedical applications. The multifunctionality of these hydrogels has been demonstrated as an in situ depot-forming delivery platform for the adjustable controlled release of proteins and small drug molecules under physiological conditions and as a structural support for adhesion, proliferation and metabolic activities of human cells. The results presented herein should be useful to the design and fabrication of tailor-made scaffolds with tunable properties that retain and exhibit sustained release of growth factors for promoting tissue regeneration.

  • 14.
    Yang, Geng
    et al.
    KTH, School of Information and Communication Technology (ICT), Electronic, Computer and Software Systems, ECS. KTH, School of Information and Communication Technology (ICT), Centres, VinnExcellence Center for Intelligence in Paper and Packaging, iPACK.
    Chen, Jian
    KTH, School of Information and Communication Technology (ICT), Electronic, Computer and Software Systems, ECS. KTH, School of Information and Communication Technology (ICT), Centres, VinnExcellence Center for Intelligence in Paper and Packaging, iPACK.
    Tenhunen, Hannu
    KTH, School of Information and Communication Technology (ICT), Electronic, Computer and Software Systems, ECS. KTH, School of Information and Communication Technology (ICT), Centres, VinnExcellence Center for Intelligence in Paper and Packaging, iPACK.
    Zheng, Li-Rong
    KTH, School of Information and Communication Technology (ICT), Electronic, Computer and Software Systems, ECS. KTH, School of Information and Communication Technology (ICT), Centres, VinnExcellence Center for Intelligence in Paper and Packaging, iPACK.
    An ASIC Solution for Intelligent Electrodes and Active-cable Used in a Wearable ECG Monitoring System2009In: BIODEVICES 2009 - Proceedings of the 2nd International Conference on Biomedical Electronics and Devices, 2009, p. 209-213Conference paper (Refereed)
    Abstract [en]

    This paper describes a digital CMOS Application Specific Integrated Circuit (ASIC) solution with the complete data acquisition and transmission for the use in a wearable electrocardiography (ECG) monitoring system. The main particularity of this system is related to the proposed reconfigurable microchip architecture for an intelligent electrode. The chip area is 2.3 mm(2) in a standard 0.18 mu m CMOS technology. The chip is operating at 24 MHz system clock with 3.3 V power supply for I/O cells and 1.8 V for the core circuit respectively. The estimated dynamic power dissipation is only 857 mu W. The post-layout simulation results show that the microchip embedded inside an intelligent electrode features ultra low power consumption and is quite feasible for a hand-held Personal Health Assistant (PHA) which uses a battery as energy source.

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