Probe Tool Research Articles

Gentle cell handling with an ultra-slow instrument: creep-manipulation of cells

In biotechnology, medicine and cell biological research, tasks like the advancement of a probe into a cell aggregate without causing cellular damage or the selection and removal of a specific cell or group from a culture surface or from a cell aggregate without undue stress require gentle cell manipulation. Currently, this requires mechanical or biochemical treatment, usually trypsination. However, these current techniques do induce cell stress and physiological reactions. We surmised that these tasks might be gently performed if the probe or recovery tool were moved sufficiently slowly, i.e. at a speed matched to the cell dynamics. Here, we show that it is possible to move an ultra-slow probe through a monolayer of cultured cells or into a 3D cell aggregate without causing obvious damage. We also demonstrate that a cell can be detached from a culture substrate by an ultra-slow probe (moving 1/500 to 1/1000 times slower than typical for a micro pipette) in the absence of any chemical treatment. This is the first time ultra-slow probes have been used to our knowledge. Finally, the practical relevance of such slow instrument movements in medicine, biotechnology and cell biology as well as possible applications and perspectives are discussed.

Metal film characterization with qualified spreading resistance

The spreading resistance probe (SRP) tool is widely used for obtaining the electrically active dopant profile in silicon. In this work, the capabilities of SRP for thin metal film (Cu/Al/TaN) characterization are investigated. It is well known that quite large correction factors (∼500) are involved in sub-100 nm silicon SRP profiling to extract the underlying carrier depth profiles from the measured raw resistances. These large correction factors also allow, in principle, for the characterization of sub-100 nm metal layers, as their measured resistances will fall in the 1–100 ohm range. Structures consisting of Cu or Al metal layers, respectively, with different thicknesses (25–400 nm) on a Ta/TaN barrier layer (∼20 nm) on SiO2 have been characterized with SRP. For calibration, the characteristics of the probe imprints have been measured with atomic force microscopy. Present results indicate that for the thinnest Cu films, it is possible to obtain a resistivity depth profile in good agreement with available theoretical predictions, based on the impact of an electron mean-free-path length of 39 nm.

Probing UPD-Induced Surface Atomic Rearrangement of Polycrystalline Gold Nanofilms with Surface Plasmon Resonance Spectroscopy and Cyclic Voltammetry

Silver underpotential deposition (UPD)-induced surface atomic rearrangement of polycrystalline gold nanofilms was probed with use of surface plasmon resonance spectroscopy (SPRs) as a novel probe tool in combination with cyclic voltammetry. Interestingly, upon repetitive electrochemical UPD and stripping of Ag, the surface structure of the resulting bare Au film is rearranged due to strong adatom−substrate interactions, which causes a large angle shift of SPR R−θ curves, in a good linear relationship with the number of UPDs, to a lower SPR angle. The n, K values of the surfacial Au monolayers before and after the repetitive Ag UPD and stripping for 27 times are found to be 0.133, 3.60 and 0.565, 9.39, respectively, corresponding to the huge shift of 1.61° to the left of the SPR minima. Cyclic voltammetry experiments in 0.10 M H2SO4 are carried out before and after the UPD treatment to examine the quality of the whole electrode surface and confirmed this change. To correlate the angle change in SPRs with t...

CO2 Offgas as a Mechanistic Probe and Scale-up Tool in N-Acylations Using Mixed Anhydrides from Amino Acids and Isobutyl Chloroformate

The reaction pathways of an N-acylation reaction, involving a mixed anhydride intermediate produced from reaction of an amino acid with isobutyl chloroformate, were analyzed using a novel technique involving the quantitation of CO2 evolved during various parts of the process. Under the normal mode of addition, in which chloroformate is added to a carboxylate anion solution, the dominant mode of yield loss to undesired product was shown to be the formation of a symmetric anhydride, implying that byproduct urethane formation was almost exclusively due to reaction of unreacted chloroformate with amine. This result suggests that inferred high concentrations of carboxylate anion present with the normal addition mode should be minimized to decrease yield loss. This hypothesis was confirmed by demonstrating that symmetric anhydride formation is almost eliminated when the reverse addition (viz., addition of carboxylate anion solution to chloroformate) was carried out. These results, in conjunction with the relati...

Learning for learning providers

Presents the findings from a study of 48 Colleges of Further Education (FE) who have participated in a diagnostic benchmarking exercise using the learning probe methodology. Learning probe has been developed from the established service probe tool (developed originally by London Business School and IBM Consulting) to support colleges of FE in their pursuit of excellence. Examines five main areas of business practice and performance consisting of business leadership; service processes; people; performance management and business results. Goes on to highlight the key strengths of the FE sector and their main areas for improvement (as defined by the sample of participating colleges). Although there are a number of practice and performance areas that need attention in particular practices relating to service processes, the sample also identifies that a number of colleges demonstrate strengths in these same areas. These issues are discussed and compared with experiences and anecdotal evidence collated from working with the FE sector over a number of years. Additionally, a comparison is made with a separate, regional benchmarking exercise that considered a number of educational organisations. Using the findings, the paper suggests a way forward for colleges to use the information which has grown out of this research. It is intended that the database will continue to grow as an information resource as learning probe becomes more widely adopted within the FE sector.

Estimating permeability distribution from 3D interval pressure transient tests

In this paper, the basic features of 3D (spatially r and z and time) interval pressure transient testing (IPTT) are described for the estimation of horizontal and vertical permeabilities and delineation of fracture and fault conductivities using the packer module and observation probe tool combination of the multiprobe wireline formation tester. Mathematical models for the pressure behavior of IPTT tests for using the packer module and the observation probes in multilayer (stratified) formations are presented. The maximum likelihood (ML) method is presented for nonlinear parameter estimation to handle uncertainty in error variances (weights) in observed data. The main advantage of the ML method over the traditional weighted least squares (WLS) is that it eliminates the trial-and-error procedure required to determine appropriate weights to be used in the WLS estimation. As shown by the examples presented in the paper, the ML method provides significant improvement in parameter estimation when working with pressure data sets of disparate orders of magnitude and noise, e.g., pressure measurements for the packer–probe and multiprobe interval tests. A field example where eight IPTT tests were conducted in a major carbonate formation is presented for characterization of vertical and horizontal layer permeabilities and vertical communication through the main producing reservoir section. These IPTT tests were conducted with a Formation Tester Dual Straddle Packer and two Probe Modules in a newly drilled well. An IPTT test at each location was interpreted using an appropriate geological model with the packer and probe pressure and flow rate measurements. The interpretation procedure consisted of identification of the different flow regimes followed by history (type curve) matching for the estimation of vertical and horizontal permeabilities for each layer. A detailed interpretation of two of the interval pressure transient tests is presented.

Methodology for the Performance Evaluation of a Conflict Probe

A conflict probe is an air traffic management tool that can predict conflicts well in advance, using information on aircraft position, speed and plans along with forecasts of wind and temperature profiles. Strategic (early) resolution of conflicts has the potential to reduce the cost associated with conflict resolution maneuvers. A conflict probe would be especially useful in a free flight environment, which is expected to have a less structured traffic flow compared to the current operating environment. This paper presents a comprehensive methodology to quantitativel y evaluate the performance of a conflict probe, using real traffic data and expanded separation criteria. The methodology is generic in nature, and can be applied to any conflict probe. It can therefore provide a framework for a comparative study of conflict probes. Several metrics of conflict probe performance have been developed and evaluated. The missed alert rate and false alert rate are primary metrics that quantify the reliability of a conflict probe; the mean conflict warning time and errors in key conflict prediction parameters such as minimum horizontal and vertical separations are important secondary metrics that quantify the accuracy of a conflict probe. Work is underway to validate the evaluation methodology developed in this work by applying it to the Center-TRACON Automation System's Conflict Probe Tool, using real traffic data from the Denver Air Route Traffic Control Center; some preliminary results are presented as an example.

Generic Metrics for the Estimation of the Prediction Accuracy of Aircraft to Aircraft Conflicts by a Strategic Conflict Probe Tool

An aircraft conflict probe is a strategic tool used by the air traffic controller to predict aircraft flight paths and to identify future conflicts. The FAA has designated the strategic conflict probe as a core function for the future ground based systems required for “Free Flight.” With these systems under development, there is a need for a generic set of metrics to quantify the performance of the conflict probe. This paper presents definitions of the two fundamental measures of the conflict prediction accuracy, missed alert and false alert probabilities. These fundamental probabilities are expanded upon to define a conflict prediction sensitivity measure, referred to as the sharpness metric, and specific examples on how the sharpness measure can be applied are presented.

Field-Test Results of a Three-Phase Holdup Measurement in Horizontal Wells With a Pulsed-Neutron Source

Summary A new method of obtaining three-phase holdup (oil/water/gas) information in horizontal wells has been field tested. The method uses the data available from a pulsed-neutron tool. This measurement uses the inelastic near/far countrate ratio in addition to the near and far carbon/oxygen (C/O) ratios. The inelastic near/far countrate ratio response is dominated by gas in the borehole, whereas the near and far C/O ratios are used to separate the water and oil contributions of the borehole and formation. By using a linear programming approach, this information is combined to produce quantitative three-phase holdup answers. Calibration ofthe measurement is achieved by the combined use of laboratory measurements and Monte Carlo modeling predictions. To obtain independent verification of the three-phase holdup answer, a local probe tool was run in combination with the pulsedneutron tool. The local probe tool is sensitive to two phases (water and hydrocarbon) and, hence, can be used for a partial verification of results. Field-test results show good agreement between the two independent measurements under various conditions of gas, oil, and water holdup in the horizontal borehole.

A magnetically levitated, automated, contact analytical probe tool

With the challenge of the shrinking dimensions in the fabrication process, demands are growing for higher precision and more powerful analytical probing stations to be used for characterization and failure analysis of integrated circuits. A magnetic levitation-based approach to analytical probing stations is proposed and investigated in this paper. This approach permits the process to be automated while maintaining better resolution and easier operation than is currently available. Further, force control can be implemented to ensure that the probe contact does not scratch the device under testing. Feedback controllers are designed and used in both the suspension and the XY positioning. The suspension motion controller is implemented in analog circuitry while the XY motion controller is implemented in a digital controller. An air gap sensor and optical position sensors are used for the position feedback. A simple open loop control method is derived for the force control. A positioning repeatability of 0.2 /spl mu/m and a force repeatability of 80 mgf are observed from the experimental results. >

Cholecystokinin Augmentation of 'Surgical' Pancreatitis

The management of acute pancreatitis has not changed appreciably throughout several decades. Recent evidence has suggested that cholecystokinin (CCK) may play an important role in pancreatic disease. Investigations into the precise role of CCK in acute pancreatitis have been hampered by the lack of a specific CCK receptor antagonist. Using a newly described, highly potent and specific CCK receptor antagonist, L-364,718, the effect of CCK in two models of acute "surgical" pancreatitis was examined: (1) the bile salt ductal perfusion model in the rat and (2) a traumatic model in the guinea pig. At a suboptimal dose for pancreatic enzyme secretion (25 pmol/kg/h), CCK was found to potentiate the severity of the ensuing pancreatitis in both models. Continuous CCK receptor blockade with L-364,718 (25 nmol/kg/h) improved biochemical, morphologic, and survival indexes. This study suggests that physiologic levels of CCK play an important permissive role in the evolution of acute pancreatitis. The use of L-364,718 as an investigative probe or therapeutic tool for acute pancreatitis is worthy of further consideration.