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Gaitas A.,PICOCAL, Inc. | Gaitas A.,Technical University of Delft | Malhotra R.,PICOCAL, Inc. | Pienta K.,Johns Hopkins University
Applied Physics Letters | Year: 2013

In the present study we engineered a micro-machined polyimide cantilever with an embedded sensing element to investigate cellular adhesion, in terms of its relative ability to stick to a cross-linker, 3,3′- dithiobis[sulfosuccinimidylpropionate], coated on the cantilever surface. To achieve this objective, we investigated adhesive properties of three human prostate cancer cell lines, namely, a bone metastasis derived human prostate cancer cell line (PC3), a brain metastasis derived human prostate cancer cell line (DU145), and a subclone of PC3 (PC3-EMT14). We found that PC3-EMT14, which displays a mesenchymal phenotype, has the least adhesion compared to PC3 and DU145, which exhibit an epithelial phenotype. © 2013 AIP Publishing LLC.

Zhu W.,PICOCAL, Inc. | Park J.S.,University of Texas at Austin | Sessler J.L.,University of Texas at Austin | Gaitas A.,PICOCAL, Inc. | Gaitas A.,Technical University of Delft
Applied Physics Letters | Year: 2011

Substantial effort has been devoted to the synthesis of molecular receptors that can function as chemosensors for nitroaromatic explosives. In spite of several advantages, these receptors suffer from low sensitivity and difficulties translating the response into the gas phase. We have combined tetrathiafulvalene-functionalized calix[4]pyrrole, a colorimetric receptor, with a polyimide microcantilever, that includes a mechanical stress sensing element. The resulting system is capable of detecting 10 ppb trinitrobenzene vapor. This represents a 30-fold improvement relative to the receptor in halogenated solvents, suggesting that this approach can provide a solution to translating the chemical response of colorimetric chemosensors into practical devices. © 2011 American Institute of Physics.

Gaitas A.,PICOCAL, Inc. | Gaitas A.,Technical University of Delft
Applied Physics Letters | Year: 2013

In this preliminary effort, a moving nano-heater directs a chemical vapor deposition reaction (nano-CVD) demonstrating a tip-based nanofabrication (TBN) method. Localized nano-CVD of copper (Cu) and copper oxide (CuO) on a silicon (Si) and silicon oxide (SiO2) substrate from gasses, namely sublimated copper acetylacetonate (Cu(acac)2), argon (Ar), and oxygen (O2), is demonstrated. This technique is applicable to other materials. © 2013 American Institute of Physics.

Gaitas A.,PICOCAL, Inc. | Gaitas A.,Technical University of Delft | Gianchandani S.,PICOCAL, Inc. | Zhu W.,PICOCAL, Inc.
Review of Scientific Instruments | Year: 2011

Thermomechanical analysis (TMA) is widely used to characterize materials and determine transition temperatures and thermal expansion coefficients. Atomic-force microscopy (AFM) microcantilevers have been used for TMA. We have developed a micromachined probe that includes two embedded sensors: one for measuring the mechanical movement of the probe (deflection) and another for providing localized heating. The new probe reduces costs and complexity and allow for portability thereby eliminating the need for an AFM. The sensitivity of the deflection element ((RR)deflection) is 0.1 ppmnm and its gauge factor is 3.24. The melting temperature of naphthalene is measured near 78.5 C. © 2011 American Institute of Physics.

Gaitas A.,PICOCAL, Inc. | Gaitas A.,Technical University of Delft | Li T.,PICOCAL, Inc. | Zhu W.,PICOCAL, Inc.
Sensors and Actuators, A: Physical | Year: 2011

We report a microcantilever probe with a 5 nm gold deflection sensor for the study of local mechanical properties such as adhesion and elasticity on a sample. The probe has a dynamic range of tens of microns, which allows for a deeper insight into the mechanical properties of materials. The gauge factor of the piezoresistive sensor is 4.1 ± 0.1 and the deflection sensitivity is 0.1 ppm/nm. Noise analysis indicates a minimum detectable deflection of ≈0.7 nm. Topographical scans are demonstrated. Studies of adhesion and stiffness of two different samples demonstrate the usefulness of the probe in the investigation of local mechanical properties. © 2011 Elsevier B.V. All rights reserved.

Gaitas A.,PICOCAL, Inc. | Gaitas A.,Technical University of Delft | French P.,Technical University of Delft
Sensors and Actuators, A: Physical | Year: 2012

Microcantilevers are used in a number of applications including atomic-force microscopy (AFM). In this work, deflection-sensing elements along with heating elements are integrated onto micromachined cantilever arrays to increase sensitivity, and reduce complexity and cost. An array of probes with 5-10 nm gold ultrathin film sensors on silicon substrates for high throughput scanning probe microscopy is developed. The deflection sensitivity is 0.2 ppm/nm. Plots of the change in resistance of the sensing element with displacement are used to calibrate the probes and determine probe contact with the substrate. Topographical scans demonstrate high throughput and nanometer resolution. The heating elements are calibrated and the thermal coefficient of resistance (TCR) is 655 ppm/K. The melting temperature of a material is measured by locally heating the material with the heating element of the cantilever while monitoring the bending with the deflection sensing element. The melting point value measured with this method is in close agreement with the reported value in literature. © 2011 Elsevier B.V. All rights reserved.

Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 199.92K | Year: 2012

NSF invites funding requests from current Small Business Innovation Research and Small Business Technology Transfer (SBIR/STTR) Phase II grantees to perform collaborative research with an Engineering Research Center (ERC). The goals of this collaborative effort are to provide a mutually beneficial research and commercialization platform where SBIR/STTR Phase II grantees can perform collaborative research with ERC faculty, researchers, and graduate students, to strengthen the capacity of their firms, and/or speed the transition of ERC advances to the marketplace. In accordance with the NSF solicitation NSF 10-617, PICOCAL, Inc has submitted a request for additional funding. The sub-awardee identified in the request is the University of Michigan. This proposal/request meets the requirements of the solicitation NSF 10-023. The proposed collaboration leverages and extends the work from PICOCALs Phase II (SBIR Phase II Award Id: 0822810) and the Engineering Research Center (ERC) for Wireless Integrated Microsystems grants. PICOCAL would be leveraging technology developed during its NSF SBIR Phase II in order to grow individual nanostructures while controlling their dimensions and orientation. During its Phase II effort, a vacuum scanning system was developed to provide nanometer positioning accuracy and accommodate specialized scanning thermal probes and probe arrays. From the ERC's side, the on-going research in the AMPP (advanced materials, processes, and packaging) thrust is relevant to the manufacturing of probes that can operate at elevated temperatures and in chemically reactive environments. This proposal provides an opportunity for the small business (PICOCAL) and the ERC (WIMS) to work synergistically together to develop a manufacturing technology for carbon nanotubes (CNT) that would have control over location, size, shape, and orientation not currently possible by other commercial methods. The SBIR Phase II to PICOCAL developed a specialized vacuum scanning system to allow nanometer accuracy when using scanning thermal probes and probe arrays. The ERC provides advanced materials expertise and additional expertise in scanning probes that will be important to the extension of the Phase II technology. The proposed collaboration will extend the Phase II technologies and translate this technology into the marketplace more rapidly. The proposed work, if successful, can have broad applications across a number of fields, including health care, energy systems, and environmental monitoring. The use of nanoprobes to control the growth and orientation of nanostructures can have a tremendous effect on nanotechnology and is something that will be synergistic with research now being pursued in the WIMS Engineering Research Center. The expected deliverables from this work include an improved probe tip, and improved probe wear. The proposed activity also helps broaden the participation underrepresented groups.

Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 150.00K | Year: 2013

This Small Business Innovation Research (SBIR) Phase I project aims to develop a micromachined patch-clamp probe that enables sub-cellular imaging, electrophysiology, and fluidic delivery at the nanoscale with control of applied force at pN levels. The probe can operate like a force sensing finger to sense contact & membrane rupture, no longer damaging cells. The small aperture allows for micro-injections and interrogation of ion channels. Additional information such as imaging, ion channel localization/mapping, and elastography can be obtained. The probe will provide new insights in the workings of cells. The broader impact/commercial potential of this project is to address the increasing need for tools to study the structure and function of single living cells. Patch clamps and micro-injectors are indispensible tools for studying cellular activity. However, these tools are plagued with numerous problems, such as damaging cells and lack of resolution, which recent innovations fail to address. The proposed nano-patch clamp addresses these problems and enables single cell analysis (SCA) for basic or clinical studies and drug discovery. The micro-machined patch clamp can become a versatile tool for SCA, which has direct implications in diagnostics, understanding disorders, and the discovery of new drugs. With the costs of clinical trials in the billion dollar range, SCA offers researchers an inexpensive way to quickly and harmlessly test and screen drug candidates on cells before testing on animals or humans. At the same time, new personalized treatments tested on the patient?s own cells, rather than one-size-fits-all treatments, have an excellent likelihood of effectively treating diseases in the future.

Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 1.26M | Year: 2013

DESCRIPTION In this SBIR Phase II PicoCal will develop a high throughput apparatus to measure changes in cell adhesion at the level of individual receptor ligand interactions in real time This tool finds critical applications in research and drug development and would allow researchers to study and manipulate adhesion by bioactive compounds to promote or inhibit physiological processes There is a significant industrial and scientific need to detect changes that can be induced by chemokines or other highly bioactive compounds in order to elucidate the different pathways of signaling mechanisms within a cell and to screen for new key compounds interfering with such pathways These findings may help to develop new therapies for cancer arteriosclerosis and autoimmune diseases like rheumatoid arthritis In research and drug development scientists have to study thousands of compounds to determine if a compound activates or inhibits adhesion In addition many diseases such as cancer are complex and require testing multiple analytes and new key compounds for accurate drug development and treatment There is a need for new tools in drug development to identify bio active compounds that inhibit or promote adhesion or modulate subtle changes in receptor affinity The instrument can also aid researchers in studying the mechanisms of cell adhesion changes such as in tumor promotion and organ specific metastasis Key research and pharmaceutical applications include leukocyte and hematopoietic stem cell adhesion to blood vessels as well as to other cells bone marrow niche or to extracellular matrix ECM proteins platelet adhesion bacteria and micro organism adhesion bio fouling PUBLIC HEALTH RELEVANCE PicoCal Inc will develop an apparatus that finds critical applications in research and drug development The instrument can aid researchers in studying the mechanisms of cancer metastasis atherosclerotic coronary artery disease and bacteria and micro organism adhesion bio fouling among others These findings may help develop new therapies for cancer arteriosclerosis and autoimmune diseases like rheumatoid arthritis

Agency: National Science Foundation | Branch: | Program: STTR | Phase: Phase I | Award Amount: 149.87K | Year: 2010

This Small Business Technology Transfer Phase I project aims to develop highly sensitive and inexpensive uncooled microbolometers using ultra-thin films of metals, metal oxides, or semi-metals. These microbolometers will be attractive for use in portable night vision devices and other thermal imaging applications that require a Noise Equivalent Temperature Difference (NETD) of less than 20 mK. We have already demonstrated metal microbolometers microfabricated from titanium thin films on SiO2/Si3N4/SiO2 cantilevers with a negative temperature coefficient of resistance (TCR) as high as - 0.67%/K (which is higher than that of bulk titanium films), with a NETD of approximately 18 mK and a 1/f noise lower than that of vanadium oxide films. The TCR can be further increased to values greater than 2%/K using alternative metals, metal oxides, or semimetals. Furthermore, thin film metallic or semimetallic microbolometers have low noise characteristics and other important advantages, including a simplified fabrication process and a lower manufacturing cost. The broader impact/commercial potential of this project is to achieve low-cost and high-sensitivity infrared (IR) detection with uncooled microbolometers, which will allow the replacement of cooled IR detectors in some low-end military and civilian applications, including night vision, navigation, biological radiometry, target discrimination, spectroscopy, and thermal profiling. Microbolometers can be further scaled down to reduce each pixel?s thermal mass, allowing a faster response to a given amount of radiation, while maintaining or improving mechanical strength. By exploring other ultra-thin film materials for uncooled IR detectors, the manufacturing cost, reliability, and uniformity can be further improved during the fabrication process. This research work will also help us further understand the electrical, optical, mechanical and thermal properties of ultrathin films of metals and semimetals. The proposed activity broadens the participation of underrepresented groups, since senior research scientists involved belong to underrepresented groups. Undergraduate involvement in this project will enhance NSF?s educational goals. Finally, the results of this project will be disseminated through publications in scientific and industry journals.

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