Los autores agradecen el apoyo financiero de la Labex-Imust.

1. Preparación de la muestra biológica Todos los experimentos descritos en este estudio fueron aprobados por el Comité del CECCAPP (Lyon, Francia) (autorización # LYONSUD_2012_004) Cuidado de Animales y el empleo, y los experimentos se llevaron a cabo bajo la supervisión de las personas autorizadas (L. Sancey, DDPP autorización # 38 05 32). <ol><li> Añadir 1 ml de H 2 O a 100 mol de nanopartículas a base de gadolinio (Gd), esperar 15 minutos y añadir 20 l de HEPES 50 mM, NaCl 1,325 M, CaCl2 20 mM a 100 l de H 2 O y 80 l de la solución primaria de nanopartículas a base de Di-s para obtener una solución de 200 l de 40 mM listas para inyectar (Ciudad: Villeurbanne, en el laboratorio). </li><li> Se inyecta la solución de nanopartículas a base de Di-s 200 l por vía intravenosa en los roedores portadores de tumores anestesiados (Ciudad: Lyon Sud (Oullins), a 15 km de laboratorio). </li><li> 1-24 horas después de la inyección, sacrificar a los ratones unad Vuelva a colocar las muestras biológicas en isopentano enfriado con nitrógeno líquido. Almacene las muestras a - 80 ° C (Ciudad: Lyon Sud (Oullins), a 15 km desde el laboratorio). </li><li> Cortar la muestra (Ciudad: generalmente Grenoble, a 100 km desde el laboratorio, voy a tratar de tener un acceso en Lyon Sud) en 100 diapositivas micras de espesor y poner las diapositivas biológicas en platos de plástico específicos (plato de Petri). Almacenar a -80 ° C. Nota: Los platos de plástico son básicamente una muestra de polímero de alta pureza. Se utilizan para evitar la interferencia con los elementos contenidos en el tejido. </li></ol> 2. Preparación de muestras para la calibración <ol><li> Preparar viales con dosis crecientes de nanopartículas a base de Gd en agua (0 nM, 100 nM, 500 nM, 1 mM, 5 mM, 10 mM, 50 mM, 100 mM, 500 mM, 1 mM y 5 mM). </li><li> Ponga un l-gota de cada solución de separación constante de 3 mm en la placa de Petri 5. </li><li> En seco a temperatura ambiente durante 20 min. </li></ol>3. Experimento LIBS <ol><li> La inicialización del programa de instalación LIBS <ol><li> Configuración de láser. Después de conectar los instrumentos, espere 10-20 minutos para la estabilización de la energía del pulso láser y el enfriamiento de la cámara ICCD hasta -20 ° C. Ajuste la energía de pulso con el atenuador. Nota: Los parámetros del láser óptimas para tejidos de mapeo son 5 ns de duración de impulsos, 1064 nm de longitud de onda y la energía de pulso de aproximadamente 4 mJ. El láser utiliza un típico Nd: YAG láser de nanosegundos. </li><li> LIBS Configuración. Establecer la posición de enfoque del láser (con respecto a la superficie de la muestra) para obtener el diámetro del cráter más pequeño (alrededor de 50 micras o menos). Nota: Esto corresponde a una focalización pulso de láser 100 micras por debajo de la superficie de la muestra. </li><li> Configuración del espectrómetro. Utilice el espectrómetro de Czerny-Turner combinado con un 1200 líneas / mm rejilla y una cámara de alta resolución ICCD temporal. Controlar todos estos dispositivos por ordenador. Establezca el valor de hendidura de entrada a 40 micras. Ajuste el rango espectral reGårding el elemento a analizar. Utilice el rango espectral que cubre 325-355 nm para detectar Di-s con alta sensibilidad, así como de Na, Cu y Ca. Establezca los parámetros ICCD con un retraso de 300 nanosegundos, una puerta de 2 microsegundos, y una ganancia de 200. </li></ol></li><li> Medición Mapping <ol><li> Coloque la muestra biológica en el soporte de la muestra LIBS motorizados. </li><li> Ajuste la altura de la muestra de acuerdo con la posición de enfoque del láser. </li><li> Tome una fotografía de alta resolución de la rebanada de la muestra. </li><li> Ajuste el módulo de mapeo del software de adquisición de LIBS para realizar un mapa con los típicos 100 x 100 puntos de medición separados por una resolución de alrededor de 100 micras. </li><li> Inicie la adquisición. Desde este punto de automatizar todo; la secuencia, así como la grabación del espectro en movimiento y el ahorro. Se requieren 40 minutos para una cartografía de los 10.000 puntos (equivalente a 1 cm 2 para una resolución de 100 m). Reagrupar todos los espectros registrados en un mismo archivo. </li><li> Cuando finished, tomar una segunda fotografía de la rebanada de la muestra </li></ol></li><li> Medición Calibración </li></ol> Con los mismos parámetros experimentales, medir las muestras de calibración (para los detalles de preparación, ver sección 2). Realizar un mapa o ficha 25 espectros (obtenido a partir de los sitios de medición en la parte central de la gota) en cada una de las gotas de calibración. 4 Análisis de espectro LIBS:. Construcción de Imágenes Químicas <ol><li> Grabar todos los espectros LIBS del mapeo del tejido y cargarlos en el análisis de software LIBS. Reste la línea de base para cada espectro y construir las imágenes químicas con escala de intensidad relativa usando un color falso. Nota: Un algoritmo recupera intensidad de las líneas específicas, tales como Gd, Cu, Na, o Ca. </li><li> Realice la misma operación en el espectro medido de la muestra calibrada para permitir el cálculo de las curvas de calibración (relación entre la intensidad y la concentración) y construir aqmapa cuantitativas a o imagen de Di-s (u otro elemento de interés). </li><li> Aplicar los tratamientos adecuados para las imágenes químicos, tales como la interpolación o suavizado. Guarde los mapas de intensidad o concentración en formato de imagen (mapa de bits). </li></ol>

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Los autores no tienen nada que revelar.

Aplicado a la muestra biológica, esta técnica permite que la imagen química, es decir, el mapeo y cuantificación, de Di-s y Si a partir de nanopartículas basadas-Di-s inyectados en diferentes órganos. A partir de los ajustes principales críticos, el control de las propiedades de láser (longitud de onda, la energía de pulso, de enfoque, y de estabilidad) es crítico para una ablación del tejido preciso y fino (es decir, una resolución de mapeo), así como para la sensibilidad. Trabajar en la ...

El amplio desarrollo de las nanopartículas para aplicaciones biológicas instó a la mejora paralela de técnicas analíticas para su cuantificación y de formación de imágenes en muestras biológicas. Por lo general, la detección y el mapeo de las nanopartículas en los órganos son hechas por fluorescencia o microscopía confocal. Desafortunadamente estos métodos requieren el etiquetado de las nanopartículas por un colorante de infrarrojo cercano que puede modificar la biodistribución de las nanopartículas, especialmente para nanopartículas muy pequeñas debido a sus propiedades hidrófobas. La detección de nanopartículas marcadas, y en especial las nanopartículas muy pequeñas (de tamaño &lt;10 nm), por lo tanto podría interferir con su biodistribución en toda la escala del cuerpo, sino también en los tejidos y de células niveles. El desarrollo de nuevos dispositivos capaces de detectar las nanopartículas sin ningún etiquetado ofrece nuevas posibilidades para el estudio de su comportamiento y la cinética. Por otra parte, el papel de los elementos traza tales como hierro y cobre en el cerebro enfermedades Und enfermedades neurodegenerativas tales como la enfermedad de Alzheimer 1, de Menkes 2,3, o Wilson 4 sugieren el interés para estudiar y localizar estos elementos en los tejidos. Diversas técnicas se han utilizado para proporcionar el mapeo elemental o microanálisis de diferentes materiales. En su artículo de revisión publicado en 2006, R. lobinski et al. Proporcionan una visión general de las técnicas estándar disponibles para microanálisis elemental en el entorno biológico, uno de los entornos más difíciles para las ciencias analíticas 5. La microsonda de electrones, que se compone de energía dispersiva de microanálisis de rayos X en un microscopio electrónico de transmisión, se puede aplicar a numerosos estudios si la concentración elemento es suficiente (&gt; 100-1.000 mg / g). Para llegar a los límites de detección más bajos, se han utilizado las siguientes técnicas: <ul><li> microsonda haz de iones usando partículas inducida por rayos X de emisión μ-PIXE (1-10 mg / g) 6 </li><li> synchrotron microanálisis radiación μ-SXRF (0,1-1 mg / g) 7 </li><li> espectrometría de masas de iones secundarios SIMS (0,1 mg / g) 8 </li><li> la ablación con láser acoplado inductivamente espectrometría de masas LA-ICP-MS (hasta 0,01 mg / g) 9,10 </li></ul> Las técnicas mencionadas anteriormente-proporcionan una resolución micrométrica como se muestra en la Tabla 1 extraído de lobinski et al. Reconstrucción 3D de las investigaciones en 2D de serie también se podría proponer para la reconstrucción de los tejidos más profundos 11. Sin embargo, todos los dispositivos y sistemas requieren tanto de los profesionales cualificados, moderados a equipos muy caros y los experimentos de larga duración (por lo general más de 4 h para una 100 m x 100 m para μ-SXRF y 10 mm x 10 mm de LA-ICP-MS ) 12. En conjunto, estos requisitos hacen microanálisis elemental muy restrictivo e incompatible con los sistemas de imagen óptica convencionales,microscopía de fluorescencia o microscopía no lineal. Otro punto que se puede mencionar es que la capacidad de medición cuantitativa es aún bastante limitado y depende de la disponibilidad de las normas de laboratorio con ajuste matricial. La mayor generalización del uso de microanálisis elemental en procesos de la industria, la geología, la biología y otras áreas de aplicaciones generará avances conceptuales y tecnológicos significativos. El propósito de la presente manuscrito es proponer soluciones para el mapeo elemental cuantitativo (o microanálisis elemental) en los tejidos biológicos con una instrumentación mesa totalmente compatible con la microscopía óptica convencional. Nuestro enfoque se basa en la espectroscopía de descomposición inducida por láser (tecnología LIBS). En LIBS, un pulso de láser se enfoca en la muestra de interés para crear la descomposición y la chispa del material. La radiación emitida atómica en el plasma se analizó posteriormente por un espectrómetro y la elementalconcentraciones mentales se pueden recuperar con las medidas de calibración realizados previamente 13,14. Las ventajas de LIBS incluyen sensibilidad (g / g para casi todos los elementos), la compacidad, la preparación de la muestra muy básico, ausencia de contacto con la muestra, respuesta instantánea y precisamente localizada (micro) análisis de superficie. Sin embargo, la aplicación de imagen química del tejido sigue siendo un reto ya que la ablación con láser de tejido debe ser controlado finamente para realizar mapas con alta resolución espacial, junto con la sensibilidad en el rango g / g 15,16. Con esa solución, no se necesita la adición de trazadores o agentes de etiquetado, que permite la detección de elementos inorgánicos directamente en su entorno nativo en los tejidos biológicos. El instrumento LIBS desarrollado en nuestro laboratorio ofrece una resolución de corriente inferior a 100 micras con una sensibilidad estimada para Di-s por debajo de 35 g / g, equivalente a 0,1 mM de 16, lo que permitela asignación de muestras grandes (&gt; 1 cm 2) dentro de 30 min. Además, el software hecho en casa facilita la adquisición y explotación de los datos. Este instrumento se utiliza para detectar, cartografiar y cuantificar la distribución tisular de gadolinio nanopartículas (Gd) basados ​​en 17 a 18 en los riñones y muestras de tumores de animales pequeños, de 1 a 24 horas después de la inyección intravenosa de las partículas (tamaño &lt;5 nm) . Elementos inorgánicos, que son intrínsecamente contenidas en un tejido biológico, tales como Fe, Ca, Na, y P, también se han detectado y fotografiado.

<table border="0" cellpadding="0" cellspacing="0" width="747">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Laser nanosecond Nd:YAG</td>
			<td style="width:129px;">Quantel</td>
			<td style="width:119px;">Brillant</td>
			<td style="width:283px;">5ns pulse witdh, wavelength 1064 nm</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Spectrometer</td>
			<td>Andor Technology</td>
			<td>Shamrock 303</td>
			<td>with 1200 l/mm blazed at 300 nm grating</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Detector ICCD</td>
			<td>Andor Technology</td>
			<td style="width:119px;">Istar</td>
			<td>2 ns temporal resolution</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">LIBS Unit</td>
			<td style="width:129px;">ILM</td>
			<td style="width:119px;"></td>
			<td>Homemade Instrumentation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;"></td>
			<td style="width:129px;"></td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Gd-based nanoparticles</td>
			<td style="width:129px;">Nano-H</td>
			<td style="width:119px;"></td>
			<td>particles</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">HEPES</td>
			<td style="width:129px;">Sigma-Aldrich</td>
			<td style="width:119px;">H4034</td>
			<td>for particle&#39;s dilution</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">CaCl2</td>
			<td style="width:129px;">Sigma-Aldrich</td>
			<td style="width:119px;">21108</td>
			<td>for particle&#39;s dilution</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">NaCl</td>
			<td style="width:129px;">Sigma-Aldrich</td>
			<td style="width:119px;">S5886</td>
			<td>for particle&#39;s dilution</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">mice</td>
			<td style="width:129px;">Charles River</td>
			<td style="width:119px;">depending of animal breeding</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">isoflurane</td>
			<td style="width:129px;">Coveto / Virbac</td>
			<td style="width:119px;"></td>
			<td>for anaesthesia - Isofluranum</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">isopentane</td>
			<td style="width:129px;">Sigma-Aldrich</td>
			<td style="width:119px;">59060</td>
			<td>to froze the sample&#160; slowly</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">liquide nitrogen</td>
			<td style="width:129px;">Air Liquide</td>
			<td style="width:119px;"></td>
			<td>to cool down the isopentane</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">cryostat</td>
			<td style="width:129px;">Leica</td>
			<td style="width:119px;">CM-3050S</td>
			<td>to slide the samples</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">petri dishes</td>
			<td style="width:129px;">Dutscher</td>
			<td style="width:119px;">353004</td>
			<td>to stick the sample</td>
		</tr>
	</tbody>
</table>

laser-induced breakdown spectroscopy: a new approach for nanoparticle's mapping and quantification in organ tissue

Espectroscopía de emisión de plasma inducida por láser se aplicó a análisis elemental de las muestras biológicas. Espectroscopía de descomposición inducida por láser (LIBS) realizado en secciones finas de tejidos de roedores: riñones y el tumor, permite la detección de elementos inorgánicos tales como (i) Na, Ca, Cu, Mg, P, y Fe, presente de forma natural en el cuerpo y (ii) Si y Di-s, detectados después de la inyección de nanopartículas a base de gadolinio. Los animales fueron sacrificados 1 a 24 horas después de la inyección intravenosa de partículas. Una exploración bidimensional de la muestra, lleva a cabo utilizando una micrométrico-etapa 3D motorizado, permite el haz de láser infrarrojo explorar la superficie con una resolución lateral de menos de 100 μ m. Imágenes químico cuantitativo de elemento de Di-s en el interior del órgano se obtuvieron con sensibilidad sub-mM. LIBS ofrece un método simple y robusto para estudiar la distribución de materiales inorgánicos sin ningún labeli específicang. Por otra parte, la compatibilidad de la instalación con el microscopio óptico estándar enfatiza su potencial para proporcionar múltiples imágenes del mismo tejido biológico con diferentes tipos de respuesta: elemental, moleculares o celulares.

Como se muestra en la Figura 1, el haz de un láser de Nd: YAG en la longitud de onda fundamental de 1064 nm se centra verticalmente hacia abajo sobre la lámina de tejido por una lente de cuarzo de 50 mm de distancia focal. La energía de pulso fue de 4 mJ y la tasa de repetición de 10 Hz. Con el fin de evitar la generación de plasma en el aire, el haz de láser se enfoca alrededor de 100 micras bajo la superficie de la muestra. No plasma de aire se observó en esta condición. Durante los experiment...

Watch this Scientific Journal Video about Laser-induced Breakdown Spectroscopy: A New Approach for Nanoparticle's Mapping and Quantification in Organ Tissue at JoVE.com

Laser-induced Breakdown Spectroscopy: A New Approach for Nanoparticle&#039;s Mapping and Quantification in Organ Tissue

Desglose espectroscopia inducida por láser se realiza en órgano fino y tejido del tumor con éxito detectado elementos naturales y gadolinio inyectado artificialmente (Gd), emitidas a partir de nanopartículas a base de D-os. Imágenes de los elementos químicos alcanzaron una resolución de 100 micras y la sensibilidad cuantitativa sub-mM. La compatibilidad de la instalación con el microscopio óptico estándar enfatiza su potencial para proporcionar múltiples imágenes de un mismo tejido biológico.

Inducida por láser Breakdown Spectroscopy: un nuevo enfoque para el mapeo y cuantificación de nanopartículas en tejidos de órganos

Emission spectroscopy of laser-induced plasma was applied to elemental analysis of biological samples. Laser-induced breakdown spectroscopy (LIBS) ...

laser-induced-breakdown-spectroscopy-new-approach-for-nanoparticle-s

Research

JoVE Journal

Engineering

Laser-induced Breakdown Spectroscopy: A New Approach for Nanoparticle's Mapping and Quantification in Organ Tissue

13.6K vistas.  CNRS - Université Lyon 1.  Desglose espectroscopia inducida por láser se realiza en órgano fino y tejido del tumor con éxito detectado elementos naturales y gadolinio inyectado artificialmente (Gd), emitidas a partir de nanopartículas a base de D-os. Imágenes de los elementos químicos alcanzaron una resolución de 100 micras y la sensibilidad cuantitativa sub-mM. La compatibilidad de la instalación con el microscopio óptico estándar enfatiza su potencial para proporcionar múltiples imág...

Video: Laser-induced Breakdown Spectroscopy: A New Approach for Nanoparticle's Mapping and Quantification in Organ Tissue

Angle-resolved Photoemission Spectroscopy At Ultra-low Temperatures

The physical properties of a material are defined by its electronic structure. Electrons in solids are characterized by energy (&omega;) and momentum (k) and the probability to find them in a particular state with given &omega; and k is described by the spectral function A(k, &omega;). This function can be directly measured in an experiment based on the well-known photoelectric effect, for the explanation of which Albert Einstein received the Nobel Prize back in 1921. In the photoelectric effect the light shone on a surface ejects electrons from the material. According to Einstein, energy conservation allows one to determine the energy of an electron inside the sample, provided the energy of the light photon and kinetic energy of the outgoing photoelectron are known. Momentum conservation makes it also possible to estimate k relating it to the momentum of the photoelectron by measuring the angle at which the photoelectron left the surface. The modern version of this technique is called Angle-Resolved Photoemission Spectroscopy (ARPES) and exploits both conservation laws in order to determine the electronic structure, i.e. energy and momentum of electrons inside the solid. In order to resolve the details crucial for understanding the topical problems of condensed matter physics, three quantities need to be minimized: uncertainty* in photon energy, uncertainty in kinetic energy of photoelectrons and temperature of the sample.
In our approach we combine three recent achievements in the field of synchrotron radiation, surface science and cryogenics. We use synchrotron radiation with tunable photon energy contributing an uncertainty of the order of 1 meV, an electron energy analyzer which detects the kinetic energies with a precision of the order of 1 meV and a He3 cryostat which allows us to keep the temperature of the sample below 1 K. We discuss the exemplary results obtained on single crystals of Sr2RuO4 and some other materials. The electronic structure of this material can be determined with an unprecedented clarity.

The overall goal of this method is to determine the low-energy electronic structure of solids at ultra-low temperatures using Angle-Resolved Photoemission Spectroscopy with synchrotron radiation.

De ángulo resuelto espectroscopia de fotoemisión a bajas temperaturas

The physical properties of a material are defined by its  electronic structure. Electrons in solids are characterized by energy (&omega;)  and momentum ...

Investigación

Ingeniería

Probing and Mapping Electrode Surfaces in Solid Oxide Fuel Cells

Solid oxide fuel cells (SOFCs) are potentially the most efficient and cost-effective solution to utilization of a wide variety of fuels beyond hydrogen 1-7. The performance of SOFCs and the rates of many chemical and energy transformation processes in energy storage and conversion devices in general are limited primarily by charge and mass transfer along electrode surfaces and across interfaces. Unfortunately, the mechanistic understanding of these processes is still lacking, due largely to the difficulty of characterizing these processes under in situ conditions. This knowledge gap is a chief obstacle to SOFC commercialization. The development of tools for probing and mapping surface chemistries relevant to electrode reactions is vital to unraveling the mechanisms of surface processes and to achieving rational design of new electrode materials for more efficient energy storage and conversion2. Among the relatively few in situ surface analysis methods, Raman spectroscopy can be performed even with high temperatures and harsh atmospheres, making it ideal for characterizing chemical processes relevant to SOFC anode performance and degradation8-12. It can also be used alongside electrochemical measurements, potentially allowing direct correlation of electrochemistry to surface chemistry in an operating cell. Proper in situ Raman mapping measurements would be useful for pin-pointing important anode reaction mechanisms because of its sensitivity to the relevant species, including anode performance degradation through carbon deposition8, 10, 13, 14 ("coking") and sulfur poisoning11, 15 and the manner in which surface modifications stave off this degradation16. The current work demonstrates significant progress towards this capability. In addition, the family of scanning probe microscopy (SPM) techniques provides a special approach to interrogate the electrode surface with nanoscale resolution. Besides the surface topography that is routinely collected by AFM and STM, other properties such as local electronic states, ion diffusion coefficient and surface potential can also be investigated17-22. In this work, electrochemical measurements, Raman spectroscopy, and SPM were used in conjunction with a novel test electrode platform that consists of a Ni mesh electrode embedded in an yttria-stabilized zirconia (YSZ) electrolyte. Cell performance testing and impedance spectroscopy under fuel containing H2S was characterized, and Raman mapping was used to further elucidate the nature of sulfur poisoning. In situ Raman monitoring was used to investigate coking behavior. Finally, atomic force microscopy (AFM) and electrostatic force microscopy (EFM) were used to further visualize carbon deposition on the nanoscale. From this research, we desire to produce a more complete picture of the SOFC anode.

We present a unique platform for characterizing electrode surfaces in solid oxide fuel cells (SOFCs) that allows simultaneous performance of multiple characterization techniques (e.g. in situ Raman spectroscopy and scanning probe microscopy alongside electrochemical measurements). Complementary information from these analyses may help to advance toward a more profound understanding of electrode reaction and degradation mechanisms, providing insights into rational design of better materials for SOFCs.

Sondeo y Cartografía superficies de los electrodos en pilas de óxido sólido

Solid oxide fuel cells (SOFCs) are potentially the most efficient and cost-effective solution to utilization of a wide variety of fuels beyond hydrogen ...

Scanning-probe Single-electron Capacitance Spectroscopy

The integration of low-temperature scanning-probe techniques and single-electron capacitance spectroscopy represents a powerful tool to study the electronic quantum structure of small systems - including individual atomic dopants in semiconductors. Here we present a capacitance-based method, known as Subsurface Charge Accumulation (SCA) imaging, which is capable of resolving single-electron charging while achieving sufficient spatial resolution to image individual atomic dopants. The use of a capacitance technique enables observation of subsurface features, such as dopants buried many nanometers beneath the surface of a semiconductor material1,2,3. In principle, this technique can be applied to any system to resolve electron motion below an insulating surface.
As in other electric-field-sensitive scanned-probe techniques4, the lateral spatial resolution of the measurement depends in part on the radius of curvature of the probe tip. Using tips with a small radius of curvature can enable spatial resolution of a few tens of nanometers. This fine spatial resolution allows investigations of small numbers (down to one) of subsurface dopants1,2. The charge resolution depends greatly on the sensitivity of the charge detection circuitry; using high electron mobility transistors (HEMT) in such circuits at cryogenic temperatures enables a sensitivity of approximately 0.01 electrons/Hz&frac12; at 0.3 K 5.

Scanning-probe single-electron capacitance spectroscopy facilitates the study of single-electron motion in localized subsurface regions. A sensitive charge-detection circuit is incorporated into a cryogenic scanning probe microscope to investigate small systems of dopant atoms beneath the surface of semiconductor samples.

Sonda de barrido de un solo electrón espectroscopia de capacitancia

The integration of low-temperature scanning-probe techniques and single-electron capacitance spectroscopy represents a powerful tool to study the ...

Measurement and Analysis of Atomic Hydrogen and Diatomic Molecular AlO, C2, CN, and TiO Spectra Following Laser-induced Optical Breakdown

In this work, we present time-resolved measurements of atomic and diatomic spectra following laser-induced optical breakdown. A typical LIBS arrangement is used. Here we operate a Nd:YAG laser at a frequency of 10 Hz at the fundamental wavelength of 1,064 nm. The 14 nsec pulses with anenergy of 190 mJ/pulse are focused to a 50 &#181;m spot size to generate a plasma from optical breakdown or laser ablation in air. The microplasma is imaged onto the entrance slit of a 0.6 m spectrometer, and spectra are recorded using an 1,800 grooves/mm grating an intensified linear diode array and optical multichannel analyzer (OMA) or an ICCD. Of interest are Stark-broadened atomic lines of the hydrogen Balmer series to infer electron density. We also elaborate on temperature measurements from diatomic emission spectra of aluminum monoxide (AlO), carbon (C2), cyanogen (CN), and titanium monoxide (TiO).
The experimental procedures include wavelength and sensitivity calibrations. Analysis of the recorded molecular spectra is accomplished by the fitting of data with tabulated line strengths. Furthermore, Monte-Carlo type simulations are performed to estimate the error margins. Time-resolved measurements are essential for the transient plasma commonly encountered in LIBS.

Measurement and Analysis of Atomic Hydrogen and Diatomic Molecular AlO, C2, CN, and TiO Spectra Following Laser-induced Optical Breakdown

Time-resolved atomic and diatomic molecular species are measured using LIBS. The spectra are collected at various time delays following the generation of optical breakdown plasma with Nd:YAG laser radiation&#160;and are analyzed to infer electron density and temperature.

Medición y Análisis de hidrógeno atómico y molecular diatómico AlO, C<sub&gt; 2</sub&gt;, CN, y el TiO Spectra siguiente desglose óptica inducida por láser

In this work, we present time-resolved measurements of atomic and diatomic spectra following laser-induced optical breakdown. A typical LIBS arrangement ...

Proton Transfer and Protein Conformation Dynamics in Photosensitive Proteins by Time-resolved Step-scan Fourier-transform Infrared Spectroscopy

Monitoring the dynamics of protonation and protein backbone conformation changes during the function of a protein is an essential step towards understanding its mechanism. Protonation and conformational changes affect the vibration pattern of amino acid side chains and of the peptide bond, respectively, both of which can be probed by infrared (IR) difference spectroscopy. For proteins whose function can be repetitively and reproducibly triggered by light, it is possible to obtain infrared difference spectra with (sub)microsecond resolution over a broad spectral range using the step-scan Fourier transform infrared technique. With ~102-103 repetitions of the photoreaction, the minimum number to complete a scan at reasonable spectral resolution and bandwidth, the noise level in the absorption difference spectra can be as low as ~10-4, sufficient to follow the kinetics of protonation changes from a single amino acid. Lower noise levels can be accomplished by more data averaging and/or mathematical processing. The amount of protein required for optimal results is between 5-100 &#181;g, depending on the sampling technique used. Regarding additional requirements, the protein needs to be first concentrated in a low ionic strength buffer and then dried to form a film. The protein film is hydrated prior to the experiment, either with little droplets of water or under controlled atmospheric humidity. The attained hydration level (g of water / g of protein) is gauged from an IR absorption spectrum. To showcase the technique, we studied the photocycle of the light-driven proton-pump bacteriorhodopsin in its native purple membrane environment, and of the light-gated ion channel channelrhodopsin-2 solubilized in detergent.

Key steps of protein function, in particular backbone conformational changes and proton transfer reactions, often take place in the microsecond to millisecond time scale. These dynamical processes can be studied by time-resolved step-scan Fourier-transform infrared spectroscopy, in particular for proteins whose function is triggered by light.

Transferencia de Protones y Proteína Conformación Dinámica de proteínas fotosensibles por Time resuelto-Step-scan transformada de Fourier espectroscopia de infrarrojo

Monitoring the dynamics of protonation and protein backbone conformation changes during the function of a protein is an essential step towards ...

In Situ Time-dependent Dielectric Breakdown in the Transmission Electron Microscope: A Possibility to Understand the Failure Mechanism in Microelectronic Devices

The time-dependent dielectric breakdown (TDDB) in on-chip interconnect stacks is one of the most critical failure mechanisms for microelectronic devices. The aggressive scaling of feature sizes, both on devices and interconnects, leads to serious challenges to ensure the required product reliability. Standard reliability tests and post-mortem failure analysis provide only limited information about the physics of failure mechanisms and degradation kinetics. Therefore it is necessary to develop new experimental approaches and procedures to study the TDDB failure mechanisms and degradation kinetics in particular. In this paper, an in situ experimental methodology in the transmission electron microscope (TEM) is demonstrated to investigate the TDDB degradation and failure mechanisms in Cu/ULK interconnect stacks. High quality imaging and chemical analysis are used to study the kinetic process. The in situ electrical test is integrated into the TEM to provide an elevated electrical field to the dielectrics. Electron tomography is utilized to characterize the directed Cu diffusion in the insulating dielectrics. This experimental procedure opens a possibility to study the failure mechanism in interconnect stacks of microelectronic products, and it could also be extended to other structures in active devices.

In Situ Time-dependent Dielectric Breakdown in the Transmission Electron Microscope: A Possibility to Understand the Failure Mechanism in Microelectronic Devices

The time-dependent dielectric breakdown (TDDB) in on-chip interconnect stacks is one of the most critical failure mechanisms for microelectronic devices. This paper demonstrates the procedure of an in situ TDDB experiment in the transmission electron microscope, which opens a possibility to study the failure mechanism in microelectronic products.

En Desglose dieléctrica Situ dependiente del tiempo en el microscopio electrónico de transmisión: una posibilidad de comprender el mecanismo de falla en los dispositivos microelectrónicos

The time-dependent dielectric breakdown (TDDB) in on-chip interconnect stacks is one of the most critical failure mechanisms for microelectronic devices. ...

Laser-induced Forward Transfer for Flip-chip Packaging of Single Dies

Flip-chip (FC) packaging is a key technology for realizing high performance, ultra-miniaturized and high-density circuits in the micro-electronics industry. In this technique the chip and/or the substrate is bumped and the two are bonded via these conductive bumps. Many bumping techniques have been developed and intensively investigated since the introduction of the FC technology in 19601 such as stencil printing, stud bumping, evaporation and electroless/electroplating2. Despite the progress that these methods have made they all suffer from one or more than one drawbacks that need to be addressed such as cost, complex processing steps, high processing temperatures, manufacturing time and most importantly the lack of flexibility. In this paper, we demonstrate a simple and cost-effective laser-based bump forming technique known as Laser-induced Forward Transfer (LIFT)3. Using the LIFT technique a wide range of bump materials can be printed in a single-step with great flexibility, high speed and accuracy at RT. In addition, LIFT enables the bumping and bonding down to chip-scale, which is critical for fabricating ultra-miniature circuitry.

We demonstrate the use of the Laser-induced Forward Transfer (LIFT) technique for flip-chip assembly of optoelectronic components. This approach provides a simple, cost-effective, low-temperature, fast and flexible solution for fine-pitch bumping and bonding on chip-scale for achieving high-density circuits for optoelectronic applications.

Transferencia Forward inducida por láser para Flip-chip de embalaje de muñones individuales

Flip-chip (FC) packaging is a key technology for realizing high performance, ultra-miniaturized and high-density circuits in the micro-electronics ...

Energy Dispersive X-ray Tomography for 3D Elemental Mapping of Individual Nanoparticles

Energy dispersive X-ray spectroscopy within the scanning transmission electron microscope (STEM) provides accurate elemental analysis with high spatial resolution, and is even capable of providing atomically resolved elemental maps. In this technique, a highly focused electron beam is incident upon a thin sample and the energy of emitted X-rays is measured in order to determine the atomic species of material within the beam path. This elementally sensitive spectroscopy technique can be extended to three dimensional tomographic imaging by acquiring multiple spectrum images with the sample tilted along an axis perpendicular to the electron beam direction.
Elemental distributions within single nanoparticles are often important for determining their optical, catalytic and magnetic properties. Techniques such as X-ray tomography and slice and view energy dispersive X-ray mapping in the scanning electron microscope provide elementally sensitive three dimensional imaging but are typically limited to spatial resolutions of &gt; 20 nm. Atom probe tomography provides near atomic resolution but preparing nanoparticle samples for atom probe analysis is often challenging. Thus, elementally sensitive techniques applied within the scanning transmission electron microscope are uniquely placed to study elemental distributions within nanoparticles of dimensions 10-100 nm.
Here, energy dispersive X-ray (EDX) spectroscopy within the STEM is applied to investigate the distribution of elements in single AgAu nanoparticles. The surface segregation of both Ag and Au, at different nanoparticle compositions, has been observed.

The use of energy dispersive X-ray tomography in the scanning transmission electron microscope to characterize elemental distributions within single nanoparticles in three dimensions is described.

La tomografía de rayos X de energía dispersiva de 3D Mapping elemental de nanopartículas individuales

Energy dispersive X-ray spectroscopy within the scanning transmission electron microscope (STEM) provides accurate elemental analysis with high spatial ...

Detection and Recovery of Palladium, Gold and Cobalt Metals from the Urban Mine Using Novel Sensors/Adsorbents Designated with Nanoscale Wagon-wheel-shaped Pores

Developing low-cost, efficient processes for recovering and recycling palladium, gold and cobalt metals from urban mine remains a significant challenge in industrialized countries. Here, the development of optical mesosensors/adsorbents (MSAs) for efficient recognition and selective recovery of Pd(II), Au(III), and Co(II) from urban mine was achieved. A simple, general method for preparing MSAs based on using high-order mesoporous monolithic scaffolds was described. Hierarchical cubic Ia3d wagon-wheel-shaped MSAs were fabricated by anchoring chelating agents (colorants) into three-dimensional pores and micrometric particle surfaces of the mesoporous monolithic scaffolds. Findings show, for the first time, evidence of controlled optical recognition of Pd(II), Au(III), and Co(II) ions and a highly selective system for recovery of Pd(II) ions (up to ~95%) in ores and industrial wastes. Furthermore, the controlled assessment processes described herein involve evaluation of intrinsic properties (e.g., visual signal change, long-term stability, adsorption efficiency, extraordinary sensitivity, selectivity, and reusability); thus, expensive, sophisticated instruments are not required. Results show evidence that MSAs will attract worldwide attention as a promising technological means of recovering and recycling palladium, gold and cobalt metals.

Because of the importance and extensive use of palladium, gold and cobalt metals in high-technology equipment, their recovery and recycling constitute an important industrial challenge. The metal recovery system described herein is a simple, low-cost means for the effective detection, removal, and recovery of these metals from the urban mine.

Detección y recuperación de paladio, oro y cobalto Metales de la Mina Urbana utilizando sensores Novela / adsorbentes designados con nanoescala Los poros en forma de rueda-Wagon

Developing low-cost, efficient processes for recovering and recycling palladium, gold and cobalt metals from urban mine remains a significant challenge in ...

Blast Quantification Using Hopkinson Pressure Bars

Near-field blast load measurement presents an issue to many sensor types as they must endure very aggressive environments and be able to measure pressures up to many hundreds of megapascals. In this respect the simplicity of the Hopkinson pressure bar has a major advantage in that while the measurement end of the Hopkinson bar can endure and be exposed to harsh conditions, the strain gauge mounted to the bar can be affixed some distance away. This allows protective housings to be utilized which protect the strain gauge but do not interfere with the measurement acquisition. The use of an array of pressure bars allows the pressure-time histories at discrete known points to be measured. This article also describes the interpolation routine used to derive pressure-time histories at un-instrumented locations on the plane of interest. Currently the technique has been used to measure loading from high explosives in free air and buried shallowly in various soils.

This protocol details the use of Hopkinson pressure bars to measure reflected blast loading from near-field explosive events. It is capable of interpolating a pressure-time history at any point on a reflective boundary and as such can be used to fully characterize the spatial and temporal variations in loading produced.

Explosión Cuantificación Utilizando listones de presión de Hopkinson

Near-field blast load measurement presents an issue to many sensor types as they must endure very aggressive environments and be able to measure pressures ...