Pub Date : 2013-11-01Epub Date: 2013-10-29DOI: 10.1116/1.4826701
Jeonghwan Kim, Kyung-Nam Kang, Anirban Sarkar, Pallavi Malempati, Dooyoung Hah, Theda Daniels-Race, Martin Feldman
Conventional Raman scattering is a workhorse technique for detecting and identifying complex molecular samples. In surface enhanced Raman scattering, a nanorough metallic surface close to the sample enhances the Raman signal enormously. In this work, the surface is on a clear epoxy substrate. The epoxy is cast on a silicon wafer, using 20 nm of gold as a mold release. This single step process already produces useful enhanced Raman signals. However, the Raman signal is further enhanced by (1) depositing additional gold on the epoxy substrate and (2) by using a combination of wet and dry etches to roughen the silicon substrate before casting the epoxy. The advantage of a clear substrate is that the Raman signal may be obtained by passing light through the substrate, with opaque samples simply placed against the surface. Results were obtained with solutions of Rhodamine 6G in deionized water over a range of concentrations from 1 nM to 1 mM. In all cases, the signal to noise ratio was greater than 10:1.
{"title":"Nanorough gold for enhanced Raman scattering.","authors":"Jeonghwan Kim, Kyung-Nam Kang, Anirban Sarkar, Pallavi Malempati, Dooyoung Hah, Theda Daniels-Race, Martin Feldman","doi":"10.1116/1.4826701","DOIUrl":"https://doi.org/10.1116/1.4826701","url":null,"abstract":"<p><p>Conventional Raman scattering is a workhorse technique for detecting and identifying complex molecular samples. In surface enhanced Raman scattering, a nanorough metallic surface close to the sample enhances the Raman signal enormously. In this work, the surface is on a clear epoxy substrate. The epoxy is cast on a silicon wafer, using 20 nm of gold as a mold release. This single step process already produces useful enhanced Raman signals. However, the Raman signal is further enhanced by (1) depositing additional gold on the epoxy substrate and (2) by using a combination of wet and dry etches to roughen the silicon substrate before casting the epoxy. The advantage of a clear substrate is that the Raman signal may be obtained by passing light through the substrate, with opaque samples simply placed against the surface. Results were obtained with solutions of Rhodamine 6G in deionized water over a range of concentrations from 1 nM to 1 mM. In all cases, the signal to noise ratio was greater than 10:1.</p>","PeriodicalId":38110,"journal":{"name":"Journal of Vacuum Science and Technology B:Nanotechnology and Microelectronics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1116/1.4826701","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31968795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2013-11-01Epub Date: 2013-10-08DOI: 10.1116/1.4823764
Haogang Cai, David Depoil, Matteo Palma, Michael P Sheetz, Michael L Dustin, Shalom J Wind
Bifunctional nanoarrays were created to simulate the immunological synapse and probe the T-cell immune response at the single-molecule level. Sub-5 nm AuPd nanodot arrays were fabricated using both e-beam and nanoimprint lithography. The nanoarrays were then functionalized by two costimulatory molecules: antibody UCHT1 Fab, which binds to the T-cell receptor (TCR) and activates the immune response, bound to metallic nanodots; and intercellular adhesion molecule-1, which enhances cell adhesion, on the surrounding area. Initial T-cell experiments show successful attachment and activation on the bifunctional nanoarrays. This nanoscale platform for single-molecule control of TCR in living T-cells provides a new approach to explore how its geometric arrangement affects T-cell activation and behavior, with potential applications in immunotherapy. This platform also serves as a general model for single-molecule nanoarrays where more than one molecular species is required.
{"title":"Bifunctional nanoarrays for probing the immune response at the single-molecule level.","authors":"Haogang Cai, David Depoil, Matteo Palma, Michael P Sheetz, Michael L Dustin, Shalom J Wind","doi":"10.1116/1.4823764","DOIUrl":"https://doi.org/10.1116/1.4823764","url":null,"abstract":"<p><p>Bifunctional nanoarrays were created to simulate the immunological synapse and probe the T-cell immune response at the single-molecule level. Sub-5 nm AuPd nanodot arrays were fabricated using both e-beam and nanoimprint lithography. The nanoarrays were then functionalized by two costimulatory molecules: antibody UCHT1 Fab, which binds to the T-cell receptor (TCR) and activates the immune response, bound to metallic nanodots; and intercellular adhesion molecule-1, which enhances cell adhesion, on the surrounding area. Initial T-cell experiments show successful attachment and activation on the bifunctional nanoarrays. This nanoscale platform for single-molecule control of TCR in living T-cells provides a new approach to explore how its geometric arrangement affects T-cell activation and behavior, with potential applications in immunotherapy. This platform also serves as a general model for single-molecule nanoarrays where more than one molecular species is required.</p>","PeriodicalId":38110,"journal":{"name":"Journal of Vacuum Science and Technology B:Nanotechnology and Microelectronics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1116/1.4823764","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31968794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2013-05-01Epub Date: 2013-03-19DOI: 10.1116/1.4795862
Hsin-Han Lin, Wen-Hwa Chen, Franklin C-N Hong
The creation of nanostructures on polycrystalline silicon wafer surface to reduce the solar reflection can enhance the solar absorption and thus increase the solar-electricity conversion efficiency of solar cells. The self-masking reactive ion etching (RIE) was studied to directly fabricate nanostructures on silicon surface without using a masking process for antireflection purpose. Reactive gases comprising chlorine (Cl2), sulfur hexafluoride (SF6), and oxygen (O2) were activated by radio-frequency plasma in an RIE system at a typical pressure of 120-130 mTorr to fabricate the nanoscale pyramids. Poly-Si wafers were etched directly without masking for 6-10 min to create surface nanostructures by varying the compositions of SF6, Cl2, and O2 gas mixtures in the etching process. The wafers were then treated with acid (KOH:H2O = 1:1) for 1 min to remove the damage layer (100 nm) induced by dry etching. The damage layer significantly reduced the solar cell efficiencies by affecting the electrical properties of the surface layer. The light reflectivity from the surface after acid treatment could be significantly reduced to <10% for the wavelengths between 500 and 900 nm. The effects of RIE and surface treatment conditions on the surface nanostructures and the optical performance as well as the efficiencies of solar cells will be presented and discussed. The authors have successfully fabricated large-area (156 × 156 mm2) subwavelength antireflection structure on poly-Si substrates, which could improve the solar cell efficiency reproducibly up to 16.27%, higher than 15.56% using wet etching.
{"title":"Improvement of polycrystalline silicon wafer solar cell efficiency by forming nanoscale pyramids on wafer surface using a self-mask etching technique.","authors":"Hsin-Han Lin, Wen-Hwa Chen, Franklin C-N Hong","doi":"10.1116/1.4795862","DOIUrl":"https://doi.org/10.1116/1.4795862","url":null,"abstract":"<p><p>The creation of nanostructures on polycrystalline silicon wafer surface to reduce the solar reflection can enhance the solar absorption and thus increase the solar-electricity conversion efficiency of solar cells. The self-masking reactive ion etching (RIE) was studied to directly fabricate nanostructures on silicon surface without using a masking process for antireflection purpose. Reactive gases comprising chlorine (Cl<sub>2</sub>), sulfur hexafluoride (SF<sub>6</sub>), and oxygen (O<sub>2</sub>) were activated by radio-frequency plasma in an RIE system at a typical pressure of 120-130 mTorr to fabricate the nanoscale pyramids. Poly-Si wafers were etched directly without masking for 6-10 min to create surface nanostructures by varying the compositions of SF<sub>6</sub>, Cl<sub>2</sub>, and O<sub>2</sub> gas mixtures in the etching process. The wafers were then treated with acid (KOH:H<sub>2</sub>O = 1:1) for 1 min to remove the damage layer (100 nm) induced by dry etching. The damage layer significantly reduced the solar cell efficiencies by affecting the electrical properties of the surface layer. The light reflectivity from the surface after acid treatment could be significantly reduced to <10% for the wavelengths between 500 and 900 nm. The effects of RIE and surface treatment conditions on the surface nanostructures and the optical performance as well as the efficiencies of solar cells will be presented and discussed. The authors have successfully fabricated large-area (156 × 156 mm<sup>2</sup>) subwavelength antireflection structure on poly-Si substrates, which could improve the solar cell efficiency reproducibly up to 16.27%, higher than 15.56% using wet etching.</p>","PeriodicalId":38110,"journal":{"name":"Journal of Vacuum Science and Technology B:Nanotechnology and Microelectronics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1116/1.4795862","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31574627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The authors developed a class of novel graphite-based field emitters, known as graphite field emitters inflamed at high temperature (GFEIHTs), which includes numerous edges and juts. The GFEIHT field emission characteristics are investigated in a vacuum tube (10-7 Pa), and an anode current exceeding 2 mA is obtained. The authors also fabricated tipped-off x-ray tubes using GFEIHTs. No degradation in the anode current is observed under the operating conditions of 16.6 kV anode voltage and 160 μA anode current. The current dispersion, defined as the standard deviation (σ)/mean over 24 h, is 2.8%. The authors successfully demonstrated radiography and x-ray fluorescence spectrometry using an x-ray tube with GFEIHT.
{"title":"X-ray tube with a graphite field emitter inflamed at high temperature.","authors":"Yusuke Iwai, Takayoshi Koike, Youhei Hayama, Atsuo Jouzuka, Tomonori Nakamura, Yoshihiro Onizuka, Motosuke Miyoshi, Hidenori Mimura","doi":"10.1116/1.4769970","DOIUrl":"https://doi.org/10.1116/1.4769970","url":null,"abstract":"<p><p>The authors developed a class of novel graphite-based field emitters, known as graphite field emitters inflamed at high temperature (GFEIHTs), which includes numerous edges and juts. The GFEIHT field emission characteristics are investigated in a vacuum tube (10<sup>-7</sup> Pa), and an anode current exceeding 2 mA is obtained. The authors also fabricated tipped-off x-ray tubes using GFEIHTs. No degradation in the anode current is observed under the operating conditions of 16.6 kV anode voltage and 160 <i>μ</i>A anode current. The current dispersion, defined as the standard deviation (σ)/mean over 24 h, is 2.8%. The authors successfully demonstrated radiography and x-ray fluorescence spectrometry using an x-ray tube with GFEIHT.</p>","PeriodicalId":38110,"journal":{"name":"Journal of Vacuum Science and Technology B:Nanotechnology and Microelectronics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1116/1.4769970","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31574626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-11-01Epub Date: 2012-10-26DOI: 10.1116/1.4764095
Marian Mankos, Khashayar Shadman, Alpha T N'diaye, Andreas K Schmid, Henrik H J Persson, Ronald W Davis
Monochromatic, aberration-corrected, dual-beam low energy electron microscopy (MAD-LEEM) is a novel imaging technique aimed at high resolution imaging of macromolecules, nanoparticles, and surfaces. MAD-LEEM combines three innovative electron-optical concepts in a single tool: a monochromator, a mirror aberration corrector, and dual electron beam illumination. The monochromator reduces the energy spread of the illuminating electron beam, which significantly improves spectroscopic and spatial resolution. The aberration corrector is needed to achieve subnanometer resolution at landing energies of a few hundred electronvolts. The dual flood illumination approach eliminates charging effects generated when a conventional, single-beam LEEM is used to image insulating specimens. The low landing energy of electrons in the range of 0 to a few hundred electronvolts is also critical for avoiding radiation damage, as high energy electrons with kilo-electron-volt kinetic energies cause irreversible damage to many specimens, in particular biological molecules. The performance of the key electron-optical components of MAD-LEEM, the aberration corrector combined with the objective lens and a magnetic beam separator, was simulated. Initial results indicate that an electrostatic electron mirror has negative spherical and chromatic aberration coefficients that can be tuned over a large parameter range. The negative aberrations generated by the electron mirror can be used to compensate the aberrations of the LEEM objective lens for a range of electron energies and provide a path to achieving subnanometer spatial resolution. First experimental results on characterizing DNA molecules immobilized on Au substrates in a LEEM are presented. Images obtained in a spin-polarized LEEM demonstrate that high contrast is achievable at low electron energies in the range of 1-10 eV and show that small changes in landing energy have a strong impact on the achievable contrast. The MAD-LEEM approach promises to significantly improve the performance of a LEEM for a wide range of applications in the biosciences, material sciences, and nanotechnology where nanometer scale resolution and analytical capabilities are required. In particular, the microscope has the potential of delivering images of unlabeled DNA strands with nucleotide-specific contrast. This simplifies specimen preparation and significantly eases the computational complexity needed to assemble the DNA sequence from individual reads.
单色、像差校正、双光束低能电子显微镜(MAD-LEEM)是一种新型成像技术,旨在对大分子、纳米粒子和表面进行高分辨率成像。MAD-LEEM 将三个创新的电子光学概念融合在一个工具中:单色器、镜像像差校正器和双电子束照明。单色仪可减少照明电子束的能量扩散,从而显著提高光谱和空间分辨率。为了在几百电子伏特的着陆能量下实现亚纳米分辨率,需要使用像差校正器。双泛光照明方法消除了传统单光束 LEEM 在对绝缘试样成像时产生的充电效应。0 到几百电子伏特范围内的低电子着陆能量对于避免辐射损伤也至关重要,因为动能达到千电子伏特的高能电子会对许多标本,特别是生物分子造成不可逆的损伤。对 MAD-LEEM 的关键电子光学组件--结合物镜的像差校正器和磁束分离器--的性能进行了模拟。初步结果表明,静电电子镜具有负球差和色差系数,可以在很大的参数范围内进行调整。电子镜产生的负像差可用于补偿 LEEM 物镜在一定电子能量范围内的像差,并为实现亚纳米级空间分辨率提供了途径。本文首次介绍了在 LEEM 中鉴定固定在金基底上的 DNA 分子的实验结果。在自旋极化 LEEM 中获得的图像表明,在 1-10 eV 的低电子能量范围内可以实现高对比度,并表明着陆能量的微小变化对可实现的对比度有很大影响。MAD-LEEM 方法有望显著提高 LEEM 的性能,广泛应用于生物科学、材料科学和纳米技术等需要纳米级分辨率和分析能力的领域。特别是,该显微镜可提供具有核苷酸特异性对比度的未标记 DNA 链图像。这不仅简化了标本制备过程,还大大降低了从单个读数组装 DNA 序列所需的计算复杂性。
{"title":"Progress toward an aberration-corrected low energy electron microscope for DNA sequencing and surface analysis.","authors":"Marian Mankos, Khashayar Shadman, Alpha T N'diaye, Andreas K Schmid, Henrik H J Persson, Ronald W Davis","doi":"10.1116/1.4764095","DOIUrl":"10.1116/1.4764095","url":null,"abstract":"<p><p>Monochromatic, aberration-corrected, dual-beam low energy electron microscopy (MAD-LEEM) is a novel imaging technique aimed at high resolution imaging of macromolecules, nanoparticles, and surfaces. MAD-LEEM combines three innovative electron-optical concepts in a single tool: a monochromator, a mirror aberration corrector, and dual electron beam illumination. The monochromator reduces the energy spread of the illuminating electron beam, which significantly improves spectroscopic and spatial resolution. The aberration corrector is needed to achieve subnanometer resolution at landing energies of a few hundred electronvolts. The dual flood illumination approach eliminates charging effects generated when a conventional, single-beam LEEM is used to image insulating specimens. The low landing energy of electrons in the range of 0 to a few hundred electronvolts is also critical for avoiding radiation damage, as high energy electrons with kilo-electron-volt kinetic energies cause irreversible damage to many specimens, in particular biological molecules. The performance of the key electron-optical components of MAD-LEEM, the aberration corrector combined with the objective lens and a magnetic beam separator, was simulated. Initial results indicate that an electrostatic electron mirror has negative spherical and chromatic aberration coefficients that can be tuned over a large parameter range. The negative aberrations generated by the electron mirror can be used to compensate the aberrations of the LEEM objective lens for a range of electron energies and provide a path to achieving subnanometer spatial resolution. First experimental results on characterizing DNA molecules immobilized on Au substrates in a LEEM are presented. Images obtained in a spin-polarized LEEM demonstrate that high contrast is achievable at low electron energies in the range of 1-10 eV and show that small changes in landing energy have a strong impact on the achievable contrast. The MAD-LEEM approach promises to significantly improve the performance of a LEEM for a wide range of applications in the biosciences, material sciences, and nanotechnology where nanometer scale resolution and analytical capabilities are required. In particular, the microscope has the potential of delivering images of unlabeled DNA strands with nucleotide-specific contrast. This simplifies specimen preparation and significantly eases the computational complexity needed to assemble the DNA sequence from individual reads.</p>","PeriodicalId":38110,"journal":{"name":"Journal of Vacuum Science and Technology B:Nanotechnology and Microelectronics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634312/pdf/JVTBD9-000030-06F402_1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31575276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-11-01Epub Date: 2012-10-29DOI: 10.1116/1.4762842
Michelle J Wilson, Yaming Jiang, Bernardo Yañez-Soto, Sara Liliensiek, William L Murphy, Paul F Nealey
Epithelial cells reside on specialized extracellular matrices that provide instructive cues to regulate and support cell function. The authors have previously demonstrated that substrate topography with dimensions similar to the native extracellular matrix (submicrometer and nanoscale features) significantly impacts corneal epithelial proliferation and migration. In this work, synthetic hydrogels were modified with both topographic and biochemical cues, where specified peptide ligands were immobilized within nanopatterned hydrogels. The efficient, systematic study of multiple instructive cues (peptide, peptide concentration, topographic dimensions), however, is contingent on the development of higher throughput platforms. Toward this goal, the authors developed a hydrogel array platform to systematically and rapidly evaluate combinations of two different peptide motifs and a range of nanoscale topographic dimensions. Specifically, distinct functional pegylated peptide ligands, RGD (GGGRGDSP) and AG73 (GRKRLQVQLSIRT), were synthesized for incorporation into an inert hydrogel network. Elastomeric stencils with arrays of millimeter-scale regions were used to spatially confine hydrogel precursor solutions on elastomeric stamps with nanoscale patterns generated by soft lithography. The resulting topographically and peptide-functionalized hydrogel arrays were used to characterize single cell migration. Epithelial cell migration speed and persistence were governed by both the biochemical and topographical cues of the underlying substrate.
{"title":"Arrays of topographically and peptide-functionalized hydrogels for analysis of biomimetic extracellular matrix properties.","authors":"Michelle J Wilson, Yaming Jiang, Bernardo Yañez-Soto, Sara Liliensiek, William L Murphy, Paul F Nealey","doi":"10.1116/1.4762842","DOIUrl":"https://doi.org/10.1116/1.4762842","url":null,"abstract":"<p><p>Epithelial cells reside on specialized extracellular matrices that provide instructive cues to regulate and support cell function. The authors have previously demonstrated that substrate topography with dimensions similar to the native extracellular matrix (submicrometer and nanoscale features) significantly impacts corneal epithelial proliferation and migration. In this work, synthetic hydrogels were modified with both topographic and biochemical cues, where specified peptide ligands were immobilized within nanopatterned hydrogels. The efficient, systematic study of multiple instructive cues (peptide, peptide concentration, topographic dimensions), however, is contingent on the development of higher throughput platforms. Toward this goal, the authors developed a hydrogel array platform to systematically and rapidly evaluate combinations of two different peptide motifs and a range of nanoscale topographic dimensions. Specifically, distinct functional pegylated peptide ligands, RGD (GGGRGDSP) and AG73 (GRKRLQVQLSIRT), were synthesized for incorporation into an inert hydrogel network. Elastomeric stencils with arrays of millimeter-scale regions were used to spatially confine hydrogel precursor solutions on elastomeric stamps with nanoscale patterns generated by soft lithography. The resulting topographically and peptide-functionalized hydrogel arrays were used to characterize single cell migration. Epithelial cell migration speed and persistence were governed by both the biochemical and topographical cues of the underlying substrate.</p>","PeriodicalId":38110,"journal":{"name":"Journal of Vacuum Science and Technology B:Nanotechnology and Microelectronics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1116/1.4762842","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31574625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-03-01Epub Date: 2012-03-22DOI: 10.1116/1.3692962
Casey N Ta, Yuko Kono, Christopher V Barback, Robert F Mattrey, Andrew C Kummel
Contrast-enhanced ultrasound (CEUS) enables highly specific time-resolved imaging of vasculature by intravenous injection of ∼2 μm gas filled microbubbles. To develop a quantitative automated diagnosis of breast tumors with CEUS, breast tumors were induced in rats by administration of N-ethyl-N-nitrosourea. A bolus injection of microbubbles was administered and CEUS videos of each tumor were acquired for at least 3 min. The time-intensity curve of each pixel within a region of interest (ROI) was analyzed to measure kinetic parameters associated with the wash-in, peak enhancement, and wash-out phases of microbubble bolus injections since it was expected that the aberrant vascularity of malignant tumors will result in faster and more diverse perfusion kinetics versus those of benign lesions. Parameters were classified using linear discriminant analysis to differentiate between benign and malignant tumors and improve diagnostic accuracy. Preliminary results with a small dataset (10 tumors, 19 videos) show 100% accuracy with fivefold cross-validation testing using as few as two choice variables for training and validation. Several of the parameters which provided the best differentiation between malignant and benign tumors employed comparative analysis of all the pixels in the ROI including enhancement coverage, fractional enhancement coverage times, and the standard deviation of the envelope curve difference normalized to the mean of the peak frame. Analysis of combinations of five variables demonstrated that pixel-by-pixel analysis produced the most robust information for tumor diagnostics and achieved 5 times greater separation of benign and malignant cases than ROI-based analysis.
{"title":"Automating tumor classification with pixel-by-pixel contrast-enhanced ultrasound perfusion kinetics.","authors":"Casey N Ta, Yuko Kono, Christopher V Barback, Robert F Mattrey, Andrew C Kummel","doi":"10.1116/1.3692962","DOIUrl":"https://doi.org/10.1116/1.3692962","url":null,"abstract":"<p><p>Contrast-enhanced ultrasound (CEUS) enables highly specific time-resolved imaging of vasculature by intravenous injection of ∼2 μm gas filled microbubbles. To develop a quantitative automated diagnosis of breast tumors with CEUS, breast tumors were induced in rats by administration of N-ethyl-N-nitrosourea. A bolus injection of microbubbles was administered and CEUS videos of each tumor were acquired for at least 3 min. The time-intensity curve of each pixel within a region of interest (ROI) was analyzed to measure kinetic parameters associated with the wash-in, peak enhancement, and wash-out phases of microbubble bolus injections since it was expected that the aberrant vascularity of malignant tumors will result in faster and more diverse perfusion kinetics versus those of benign lesions. Parameters were classified using linear discriminant analysis to differentiate between benign and malignant tumors and improve diagnostic accuracy. Preliminary results with a small dataset (10 tumors, 19 videos) show 100% accuracy with fivefold cross-validation testing using as few as two choice variables for training and validation. Several of the parameters which provided the best differentiation between malignant and benign tumors employed comparative analysis of all the pixels in the ROI including enhancement coverage, fractional enhancement coverage times, and the standard deviation of the envelope curve difference normalized to the mean of the peak frame. Analysis of combinations of five variables demonstrated that pixel-by-pixel analysis produced the most robust information for tumor diagnostics and achieved 5 times greater separation of benign and malignant cases than ROI-based analysis.</p>","PeriodicalId":38110,"journal":{"name":"Journal of Vacuum Science and Technology B:Nanotechnology and Microelectronics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1116/1.3692962","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31476333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-03-01Epub Date: 2012-03-05DOI: 10.1116/1.3692250
Robert M Taylor, Dale L Huber, Todd C Monson, Victor Esch, Laurel O Sillerud
The authors report the synthesis, from simple salts, and the physical characterization of superparamagnetic iron platinum nanoparticles (SIPPs) suitable for use as contrast agents in magnetic resonance imaging. The properties of these particles were determined by means of transmission electron microscopy (TEM), thermogravimetric analysis, inductively coupled plasma-optical emission spectroscopy (ICP-OES), superconducting quantum interference device (SQUID) magnetometry, and nuclear magnetic resonance relaxivity at 4.7 T. TEM showed that the diameters of the particles ranged from 9.3 to 10 nm, depending on the mole ratio of iron to platinum precursors, and on the concentration of octadecylamine (ODA) used in their preparation. The iron to platinum stoichiometry determined by ICP-OES varied from 1.4:1 to 3.7:1 and was similarly dependent on the initial mole ratios of iron and platinum salts, as well as on the concentration of ODA in the reaction. SQUID magnetometry showed that the SIPPs were superparamagnetic and had magnetic moments that increased with increasing iron content from 62 to 72 A·m2/kg Fe. The measured relaxivities of the SIPPs at 4.7 T were higher than commercially available superparamagnetic iron oxide nanoparticles, suggesting that these particles may be superior contrast agents in T2-weighted magnetic resonance imaging.
{"title":"Structural and magnetic characterization of superparamagnetic iron platinum nanoparticle contrast agents for magnetic resonance imaging.","authors":"Robert M Taylor, Dale L Huber, Todd C Monson, Victor Esch, Laurel O Sillerud","doi":"10.1116/1.3692250","DOIUrl":"https://doi.org/10.1116/1.3692250","url":null,"abstract":"<p><p>The authors report the synthesis, from simple salts, and the physical characterization of superparamagnetic iron platinum nanoparticles (SIPPs) suitable for use as contrast agents in magnetic resonance imaging. The properties of these particles were determined by means of transmission electron microscopy (TEM), thermogravimetric analysis, inductively coupled plasma-optical emission spectroscopy (ICP-OES), superconducting quantum interference device (SQUID) magnetometry, and nuclear magnetic resonance relaxivity at 4.7 T. TEM showed that the diameters of the particles ranged from 9.3 to 10 nm, depending on the mole ratio of iron to platinum precursors, and on the concentration of octadecylamine (ODA) used in their preparation. The iron to platinum stoichiometry determined by ICP-OES varied from 1.4:1 to 3.7:1 and was similarly dependent on the initial mole ratios of iron and platinum salts, as well as on the concentration of ODA in the reaction. SQUID magnetometry showed that the SIPPs were superparamagnetic and had magnetic moments that increased with increasing iron content from 62 to 72 A·m<sup>2</sup>/kg Fe. The measured relaxivities of the SIPPs at 4.7 T were higher than commercially available superparamagnetic iron oxide nanoparticles, suggesting that these particles may be superior contrast agents in T<sub>2</sub>-weighted magnetic resonance imaging.</p>","PeriodicalId":38110,"journal":{"name":"Journal of Vacuum Science and Technology B:Nanotechnology and Microelectronics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1116/1.3692250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32748619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J E Baio, T Weidner, G Interlandi, C Mendoza-Barrera, H E Canavan, R Michel, D G Castner
In this study the binding and assembly of bovine serum albumin (BSA) onto three different calcium phosphate phases (hydroxyapatite, dibasic calcium phosphate dihydrate, and β-tricalcium phosphate) was investigated using a combination of X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). XPS was used to record adsorption isotherms and to quantify the amount of BSA adsorbed onto the different CaP surfaces. On all three surfaces a monolayer of adsorbed BSA was formed. ToF-SIMS was then used to investigate how the structure of BSA changes upon surface binding. ToF-SIMS data from BSA films on the three CaP surfaces showed intensity differences of secondary ions originating from both hydrophobic and hydrophilic amino acids. For a more quantitative examination of structural changes, we developed a ratio comparing the sum of intensities of secondary ions from hydrophobic and hydrophilic residues. A small, but statistically significant, increase in the value of this ratio (7%) was observed between a BSA film on hydroxyapatite versus dibasic calcium phosphate dihydrate. From this ratio we can make some initial hypotheses about what specific changes in BSA structure relate to these differences observed in the ToF-SIMS data.
{"title":"Probing Albumin Adsorption onto Calcium Phosphates by XPS and ToF-SIMS.","authors":"J E Baio, T Weidner, G Interlandi, C Mendoza-Barrera, H E Canavan, R Michel, D G Castner","doi":"10.1116/1.3613919","DOIUrl":"https://doi.org/10.1116/1.3613919","url":null,"abstract":"<p><p>In this study the binding and assembly of bovine serum albumin (BSA) onto three different calcium phosphate phases (hydroxyapatite, dibasic calcium phosphate dihydrate, and β-tricalcium phosphate) was investigated using a combination of X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). XPS was used to record adsorption isotherms and to quantify the amount of BSA adsorbed onto the different CaP surfaces. On all three surfaces a monolayer of adsorbed BSA was formed. ToF-SIMS was then used to investigate how the structure of BSA changes upon surface binding. ToF-SIMS data from BSA films on the three CaP surfaces showed intensity differences of secondary ions originating from both hydrophobic and hydrophilic amino acids. For a more quantitative examination of structural changes, we developed a ratio comparing the sum of intensities of secondary ions from hydrophobic and hydrophilic residues. A small, but statistically significant, increase in the value of this ratio (7%) was observed between a BSA film on hydroxyapatite versus dibasic calcium phosphate dihydrate. From this ratio we can make some initial hypotheses about what specific changes in BSA structure relate to these differences observed in the ToF-SIMS data.</p>","PeriodicalId":38110,"journal":{"name":"Journal of Vacuum Science and Technology B:Nanotechnology and Microelectronics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1116/1.3613919","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30405403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}