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  • 1
    Publication Date: 2001-02-07
    Description: Soft lithography is an alternative to silicon-based micromachining that uses replica molding of nontraditional elastomeric materials to fabricate stamps and microfluidic channels. We describe here an extension to the soft lithography paradigm, multilayer soft lithography, with which devices consisting of multiple layers may be fabricated from soft materials. We used this technique to build active microfluidic systems containing on-off valves, switching valves, and pumps entirely out of elastomer. The softness of these materials allows the device areas to be reduced by more than two orders of magnitude compared with silicon-based devices. The other advantages of soft lithography, such as rapid prototyping, ease of fabrication, and biocompatibility, are retained.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Unger, M A -- Chou, H P -- Thorsen, T -- Scherer, A -- Quake, S R -- DA-9121/DA/NIDA NIH HHS/ -- NS-11756/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2000 Apr 7;288(5463):113-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Applied Physics, California Institute of Technology, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10753110" target="_blank"〉PubMed〈/a〉
    Keywords: Adhesiveness ; *Biocompatible Materials ; Elasticity ; Materials Testing ; Pressure ; *Prostheses and Implants ; *Silicone Elastomers
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-09-28
    Description: We developed high-density microfluidic chips that contain plumbing networks with thousands of micromechanical valves and hundreds of individually addressable chambers. These fluidic devices are analogous to electronic integrated circuits fabricated using large-scale integration. A key component of these networks is the fluidic multiplexor, which is a combinatorial array of binary valve patterns that exponentially increases the processing power of a network by allowing complex fluid manipulations with a minimal number of inputs. We used these integrated microfluidic networks to construct the microfluidic analog of a comparator array and a microfluidic memory storage device whose behavior resembles random-access memory.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thorsen, Todd -- Maerkl, Sebastian J -- Quake, Stephen R -- New York, N.Y. -- Science. 2002 Oct 18;298(5593):580-4. Epub 2002 Sep 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biochemistry and Molecular Biophysics Option, Department of Applied Physics, California Institute of Technology, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12351675" target="_blank"〉PubMed〈/a〉
    Keywords: Biochemistry/*instrumentation/methods ; Bromphenol Blue ; Coloring Agents ; Computers ; Cytochrome-c Peroxidase/metabolism ; Electronics ; Escherichia coli/enzymology/isolation & purification ; Gene Expression Profiling/*instrumentation ; Green Fluorescent Proteins ; Luminescent Proteins/metabolism ; Miniaturization ; Pressure ; Silicones
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-11-25
    Description: Soft materials are finding applications in areas ranging from microfluidic device technology to nanofabrication. We review recent work in these areas, discuss the motivation for device fabrication with soft materials, and describe applications of soft materials. In particular, we discuss active microfluidic devices for cell sorting and biochemical assays, replication-molded optics with subdiffraction limit features, and nanometer-scale resonators and wires formed from single-molecule DNA templates as examples of how the special properties of soft materials address outstanding problems in device fabrication.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Quake, S R -- Scherer, A -- New York, N.Y. -- Science. 2000 Nov 24;290(5496):1536-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Applied Physics, MS 128-95, California Institute of Technology, Pasadena, CA 91125, USA. quake@caltech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11090344" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Engineering/instrumentation/methods ; *Biotechnology/instrumentation/methods ; *Elastomers ; Electronics ; Engineering/instrumentation/methods ; Mechanics ; *Miniaturization ; Optics and Photonics ; *Technology/instrumentation/methods ; Templates, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2009-02-06
    Description: The metabolism of oxygen, although central to life, produces reactive oxygen species (ROS) that have been implicated in processes as diverse as cancer, cardiovascular disease and ageing. It has recently been shown that central nervous system stem cells and haematopoietic stem cells and early progenitors contain lower levels of ROS than their more mature progeny, and that these differences are critical for maintaining stem cell function. We proposed that epithelial tissue stem cells and their cancer stem cell (CSC) counterparts may also share this property. Here we show that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells. Notably, subsets of CSCs in some human and murine breast tumours contain lower ROS levels than corresponding non-tumorigenic cells (NTCs). Consistent with ROS being critical mediators of ionizing-radiation-induced cell killing, CSCs in these tumours develop less DNA damage and are preferentially spared after irradiation compared to NTCs. Lower ROS levels in CSCs are associated with increased expression of free radical scavenging systems. Pharmacological depletion of ROS scavengers in CSCs markedly decreases their clonogenicity and results in radiosensitization. These results indicate that, similar to normal tissue stem cells, subsets of CSCs in some tumours contain lower ROS levels and enhanced ROS defences compared to their non-tumorigenic progeny, which may contribute to tumour radioresistance.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778612/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778612/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Diehn, Maximilian -- Cho, Robert W -- Lobo, Neethan A -- Kalisky, Tomer -- Dorie, Mary Jo -- Kulp, Angela N -- Qian, Dalong -- Lam, Jessica S -- Ailles, Laurie E -- Wong, Manzhi -- Joshua, Benzion -- Kaplan, Michael J -- Wapnir, Irene -- Dirbas, Frederick M -- Somlo, George -- Garberoglio, Carlos -- Paz, Benjamin -- Shen, Jeannie -- Lau, Sean K -- Quake, Stephen R -- Brown, J Martin -- Weissman, Irving L -- Clarke, Michael F -- R01 CA100225/CA/NCI NIH HHS/ -- R01 CA100225-05/CA/NCI NIH HHS/ -- U54 CA126524/CA/NCI NIH HHS/ -- U54 CA126524-04/CA/NCI NIH HHS/ -- England -- Nature. 2009 Apr 9;458(7239):780-3. doi: 10.1038/nature07733.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19194462" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/physiopathology ; Cells, Cultured ; DNA Damage/genetics/radiation effects ; Female ; Gene Expression ; Humans ; Mammary Glands, Human/cytology/metabolism ; Mice ; Mice, Inbred C57BL ; Neoplastic Stem Cells/*metabolism/*radiation effects ; Radiation Tolerance/*physiology ; Reactive Oxygen Species/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2010-06-29
    Description: Cells operate in dynamic environments using extraordinary communication capabilities that emerge from the interactions of genetic circuitry. The mammalian immune response is a striking example of the coordination of different cell types. Cell-to-cell communication is primarily mediated by signalling molecules that form spatiotemporal concentration gradients, requiring cells to respond to a wide range of signal intensities. Here we use high-throughput microfluidic cell culture and fluorescence microscopy, quantitative gene expression analysis and mathematical modelling to investigate how single mammalian cells respond to different concentrations of the signalling molecule tumour-necrosis factor (TNF)-alpha, and relay information to the gene expression programs by means of the transcription factor nuclear factor (NF)-kappaB. We measured NF-kappaB activity in thousands of live cells under TNF-alpha doses covering four orders of magnitude. We find, in contrast to population-level studies with bulk assays, that the activation is heterogeneous and is a digital process at the single-cell level with fewer cells responding at lower doses. Cells also encode a subtle set of analogue parameters to modulate the outcome; these parameters include NF-kappaB peak intensity, response time and number of oscillations. We developed a stochastic mathematical model that reproduces both the digital and analogue dynamics as well as most gene expression profiles at all measured conditions, constituting a broadly applicable model for TNF-alpha-induced NF-kappaB signalling in various types of cells. These results highlight the value of high-throughput quantitative measurements with single-cell resolution in understanding how biological systems operate.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105528/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105528/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tay, Savas -- Hughey, Jacob J -- Lee, Timothy K -- Lipniacki, Tomasz -- Quake, Stephen R -- Covert, Markus W -- K99CA125994/CA/NCI NIH HHS/ -- R00 CA125994/CA/NCI NIH HHS/ -- R00 CA125994-05/CA/NCI NIH HHS/ -- R01-GM086885/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Jul 8;466(7303):267-71. doi: 10.1038/nature09145. Epub 2010 Jun 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20581820" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Active Transport, Cell Nucleus/drug effects ; Animals ; Cell Culture Techniques ; Cell Nucleus/drug effects/metabolism ; Cell Survival ; Dose-Response Relationship, Drug ; Gene Expression Profiling/*methods ; Gene Expression Regulation/*drug effects ; High-Throughput Screening Assays/*methods ; Mice ; Microfluidic Analytical Techniques ; Microscopy, Fluorescence ; Models, Biological ; NF-kappa B/*metabolism ; Signal Transduction/*drug effects/*physiology ; Stochastic Processes ; Substrate Specificity ; Time Factors ; Tumor Necrosis Factor-alpha/*pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2007-01-16
    Description: A major goal of systems biology is to predict the function of biological networks. Although network topologies have been successfully determined in many cases, the quantitative parameters governing these networks generally have not. Measuring affinities of molecular interactions in high-throughput format remains problematic, especially for transient and low-affinity interactions. We describe a high-throughput microfluidic platform that measures such properties on the basis of mechanical trapping of molecular interactions. With this platform we characterized DNA binding energy landscapes for four eukaryotic transcription factors; these landscapes were used to test basic assumptions about transcription factor binding and to predict their in vivo function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maerkl, Sebastian J -- Quake, Stephen R -- New York, N.Y. -- Science. 2007 Jan 12;315(5809):233-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biochemistry and Molecular Biophysics Option, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17218526" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism ; Basic Helix-Loop-Helix Transcription Factors/*metabolism ; Computational Biology ; Computer Simulation ; DNA/*metabolism ; DNA, Fungal/genetics/metabolism ; DNA-Binding Proteins/metabolism ; E-Box Elements ; Gene Expression Regulation, Fungal ; Helix-Loop-Helix Motifs ; Humans ; *Microfluidic Analytical Techniques ; Oligonucleotide Array Sequence Analysis ; Protein Binding ; Protein Isoforms/metabolism ; Regulatory Sequences, Nucleic Acid ; Repressor Proteins/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; *Systems Biology ; Templates, Genetic ; Thermodynamics ; Transcription Factors/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2009-05-09
    Description: Despite tremendous progress in understanding the nature of the immune system, the full diversity of an organism's antibody repertoire is unknown. We used high-throughput sequencing of the variable domain of the antibody heavy chain from 14 zebrafish to analyze VDJ usage and antibody sequence. Zebrafish were found to use between 50 and 86% of all possible VDJ combinations and shared a similar frequency distribution, with some correlation of VDJ patterns between individuals. Zebrafish antibodies retained a few thousand unique heavy chains that also exhibited a shared frequency distribution. We found evidence of convergence, in which different individuals made the same antibody. This approach provides insight into the breadth of the expressed antibody repertoire and immunological diversity at the level of an individual organism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086368/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086368/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weinstein, Joshua A -- Jiang, Ning -- White, Richard A 3rd -- Fisher, Daniel S -- Quake, Stephen R -- DP1 OD000251/OD/NIH HHS/ -- DP1 OD000251-04/OD/NIH HHS/ -- DP1 OD000251-05/OD/NIH HHS/ -- DP1 OD000251-06/OD/NIH HHS/ -- New York, N.Y. -- Science. 2009 May 8;324(5928):807-10. doi: 10.1126/science.1170020.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biophysics Program, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19423829" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies/genetics ; Antibody Diversity ; Base Sequence ; Complementarity Determining Regions/*genetics ; Computational Biology ; Female ; Gene Library ; *Genes, Immunoglobulin Heavy Chain ; Immunoglobulin Heavy Chains/*genetics ; Immunoglobulin Joining Region/genetics ; Immunoglobulin M/*genetics ; Male ; Molecular Sequence Data ; Recombination, Genetic ; Sequence Analysis, DNA ; VDJ Exons ; Zebrafish/genetics/*immunology
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  • 8
    Publication Date: 2013-07-28
    Description: Histocompatibility is the basis by which multicellular organisms of the same species distinguish self from nonself. Relatively little is known about the mechanisms underlying histocompatibility reactions in lower organisms. Botryllus schlosseri is a colonial urochordate, a sister group of vertebrates, that exhibits a genetically determined natural transplantation reaction, whereby self-recognition between colonies leads to formation of parabionts with a common vasculature, whereas rejection occurs between incompatible colonies. Using genetically defined lines, whole-transcriptome sequencing, and genomics, we identified a single gene that encodes self-nonself and determines "graft" outcomes in this organism. This gene is significantly up-regulated in colonies poised to undergo fusion and/or rejection, is highly expressed in the vasculature, and is functionally linked to histocompatibility outcomes. These findings establish a platform for advancing the science of allorecognition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810301/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810301/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Voskoboynik, Ayelet -- Newman, Aaron M -- Corey, Daniel M -- Sahoo, Debashis -- Pushkarev, Dmitry -- Neff, Norma F -- Passarelli, Benedetto -- Koh, Winston -- Ishizuka, Katherine J -- Palmeri, Karla J -- Dimov, Ivan K -- Keasar, Chen -- Fan, H Christina -- Mantalas, Gary L -- Sinha, Rahul -- Penland, Lolita -- Quake, Stephen R -- Weissman, Irving L -- 1R01AG037968/AG/NIA NIH HHS/ -- 1R56AI089968/AI/NIAID NIH HHS/ -- K12 HL087746/HL/NHLBI NIH HHS/ -- K99 CA151673/CA/NCI NIH HHS/ -- K99CA151673-01A1/CA/NCI NIH HHS/ -- R01 AG037968/AG/NIA NIH HHS/ -- R01 GM100315/GM/NIGMS NIH HHS/ -- R01GM100315/GM/NIGMS NIH HHS/ -- R56 AI089968/AI/NIAID NIH HHS/ -- T32 CA009302/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Jul 26;341(6144):384-7. doi: 10.1126/science.1238036.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. ayeletv@stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23888037" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; *Genes ; Genome ; Genotype ; Histocompatibility/*genetics ; Immune Tolerance ; Molecular Sequence Data ; Sequence Analysis, DNA ; Transcriptome ; Up-Regulation ; Urochordata/*genetics/*immunology/physiology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-05-10
    Description: We demonstrate microscopic fluidic control and memory elements through the use of an aqueous viscoelastic polymer solution as a working fluid. By exploiting the fluid's non-Newtonian rheological properties, we were able to demonstrate both a flux stabilizer and a bistable flip-flop memory. These circuit elements are analogous to their solid-state electronic counterparts and could be used as components of control systems for integrated microfluidic devices. Such miniaturized fluidic circuits are insensitive to electromagnetic interference and may also find medical applications for implanted drug-delivery devices.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Groisman, Alex -- Enzelberger, Markus -- Quake, Stephen R -- New York, N.Y. -- Science. 2003 May 9;300(5621):955-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Applied Physics, California Institute of Technology, MS 128-95, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12738857" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2005-12-17
    Description: Microreactor technology has shown potential for optimizing synthetic efficiency, particularly in preparing sensitive compounds. We achieved the synthesis of an [(18)F]fluoride-radiolabeled molecular imaging probe, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), in an integrated microfluidic device. Five sequential processes-[18F]fluoride concentration, water evaporation, radiofluorination, solvent exchange, and hydrolytic deprotection-proceeded with high radio-chemical yield and purity and with shorter synthesis time relative to conventional automated synthesis. Multiple doses of [18F]FDG for positron emission tomography imaging studies in mice were prepared. These results, which constitute a proof of principle for automated multistep syntheses at the nanogram to microgram scale, could be generalized to a range of radiolabeled substrates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Chung-Cheng -- Sui, Guodong -- Elizarov, Arkadij -- Shu, Chengyi Jenny -- Shin, Young-Shik -- Dooley, Alek N -- Huang, Jiang -- Daridon, Antoine -- Wyatt, Paul -- Stout, David -- Kolb, Hartmuth C -- Witte, Owen N -- Satyamurthy, Nagichettiar -- Heath, James R -- Phelps, Michael E -- Quake, Stephen R -- Tseng, Hsian-Rong -- 5T32-GM07616/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2005 Dec 16;310(5755):1793-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, California Institute of Technology, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16357255" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Automation ; Fluorides ; Fluorodeoxyglucose F18/*chemical synthesis ; Gas Chromatography-Mass Spectrometry ; Mice ; *Microfluidics ; Miniaturization ; Molecular Probes/*chemical synthesis ; Positron-Emission Tomography ; Radiopharmaceuticals/*chemical synthesis ; Rhabdomyosarcoma/radionuclide imaging ; Solvents ; Tomography, Emission-Computed
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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