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PubMed2002

An automated computer system to support ultra high throughput SNP genotyping.

Celera Genomics has constructed an automated computer system to support ultra high-throughput SNP genotyping that satisfies the increasing demand that disease association studies are placing on current genotyping facilities. This system consists of the seamless integration of target SNP selection, automated oligo design, in silico assay quality validation, laboratory management of samples, reagents and plates, automated allele calling, optional manual review of autocalls, regular status reports, and linkage disequilibrium analysis. Celera has proven the system by generating over 2.5 million genotypes from more than 10,000 SNPs, and is approaching the target capacity of over 10,000 genotypes per machine per hour using limited human intervention with state of the art laboratory hardware.

Automation↗
PubMed1977

Automated diagnosis of congenital dislocation of the hip.

A study of the automated diagnosis of luxatio coxae congenita (LCC) was performed to establish an automated screening system for hip radiographs. A specific parameter with high diagnostic accuracy was selected by the use of information theory. Pattern recognition programs were written to extract the parameter from digitized hip radiographs. Parameter measurement was performed on 10 radiographs and compared with manual measurements. Results showed good agreement with measurements obtained by specialists. This study confirms the possibilities of automated diagnosis of LCC.

Diagnosis, Computer-Assisted↗
PubMedDate not supplied

AutoCyte SCREEN interactive automated primary cytology screening system. A preliminary evaluation.

OBJECTIVE: To perform a preliminary evaluation of the relative sensitivity of a new interactive automated cytology screening system (AutoCyte SCREEN, AutoCyte, Inc., Elon College, North Carolina, U.S.A.) designed as a primary screening system for AutoCyte PREP monolayer slides (AutoCyte). STUDY DESIGN: Monolayer slides were prepared and evaluated in a masked review both manually and using the automated system. Human and machine performance was monitored and measured. RESULTS: Five hundred eighty-three monolayer preparations, including 56 clearly abnormal cases, were evaluated. The dual and combined computer and cytologist image evaluation resulted in a relatively low false positive rate, 20.8%, and 1.8% false negative rate. Use of the system was efficient, significantly reducing cytotechnologist screening time. CONCLUSION: The integrated AutoCyte cell preparation and automated screening approach seems to hold significant promise for primary cytology screening applications.

Adenocarcinoma↗
PubMed2005

Automated oscillometric determination of the ankle-brachial index provides accuracy necessary for office practice.

Peripheral arterial disease (PAD) remains underdiagnosed by primary care and cardiovascular physicians. The office-based assessment of PAD is limited by the need for specialized equipment and the time required for performance of the ankle-brachial index (ABI). We explored whether the accuracy of automated ABI measurement by oscillometry compared favorably with the gold-standard method using continuous-wave Doppler ultrasound. Consecutive patients referred to our university hospital noninvasive vascular laboratory for ABI measurement were invited for participation. Of 205 patients, 201 participated, including 55 with PAD. The ABI was measured by automated oscillometry and Doppler ultrasound. The test of trends revealed a correlation coefficient of 0.78 in the left leg and 0.78 in the right leg (P<0.01 for both). The mean ABI difference between methods was 0.04+/-0.01 and 0.06+/-0.01, respectively, in the left and right legs. The differences between the methods followed a normal distribution. Oscillometric determination of the ABI provides an accurate determination of the ABI in an outpatient population. Our findings show automated oscillometry to be a reliable and easier method of ABI measurement, lowering the barrier to incorporation of this diagnostic test into clinical practice.

Aged↗
PubMed1997

A new automated computerized analyzing system simplifies readings and reduces the variability in ultrasound measurement of intima-media thickness.

BACKGROUND AND PURPOSE: A computerized analyzing system with manual tracing of echo interfaces for measurement of intima-media thickness and lumen diameter in carotid and femoral arteries was previously developed by our research group and has been used for many years in several laboratories. However, manual measurements are not only time consuming, but the results from these readings are also dependent on training and subjective judgement. A further problem is the observed drift in measurements over time. A new computerized technique for automatic detection of echo interfaces was therefore developed. The aim of this study was to evaluate the new automated computerized analyzing system. METHODS: The new system is based on dynamic programming and includes optional interactive modification by the human operator. Local measurements of vessel echo intensity, intensity gradient, and boundary continuity are extracted by image analysis techniques and included as weighed terms in a cost function. The dynamic programming procedure is used for determining the optimal location of the vessel interfaces in a way that the cost function is minimized. RESULTS: With the new automated computerized analyzing system the measurement results were less dependent on the reader's experience, and the variability between readers was less compared with the old manual analyzing system. The measurements were also less time consuming. CONCLUSIONS: The new automated analyzing system will not only greatly increase the speed of measurements but also reduce the variability between readers. It should also reduce the variability between different laboratories if the same analyzing program is used. Furthermore, the new system will probably prevent the problem with drift in measurements over time.

Automation↗
PubMed2000

Evaluation of new online automated embolic signal detection algorithm, including comparison with panel of international experts.

BACKGROUND AND PURPOSE: The clinical application of Doppler detection of circulating cerebral emboli will depend on a reliable automated system of embolic signal detection; such a system is not currently available. Previous studies have shown that frequency filtering increases the ratio of embolic signal to background signal intensity and that the incorporation of such an approach into an offline automated detection system markedly improved performance. In this study, we evaluated an online version of the system. In a single-center study, we compared its performance with that of a human expert on data from 2 clinical situations, carotid stenosis and the period immediately after carotid endarterectomy. Because the human expert is currently the "gold standard" for embolic signal detection, we also compared the performance of the system with an international panel of human experts in a multicenter study. METHODS: In the single-center evaluation, the performance of the software was tested against that of a human expert on 20 hours of data from 21 patients with carotid stenosis and 18 hours of data from 9 patients that was recorded after carotid endarterectomy. For the multicenter evaluation, a separate 2-hour data set, recorded from 5 patients after carotid endarterectomy, was analyzed by 6 different human experts using the same equipment and by the software. Agreement was assessed by determining the probability of agreement. RESULTS: In the 20 hours of carotid stenosis data, there were 140 embolic signals with an intensity of > or =7 dB. With the software set at a confidence threshold of 60%, a sensitivity of 85.7% and a specificity of 88.9% for detection of embolic signals were obtained. At higher confidence thresholds, a specificity >95% could be obtained, but this was at the expense of a lower sensitivity. In the 18 hours of post-carotid endarterectomy data, there were 411 embolic signals of > or =7-dB intensity. When the same confidence threshold was used, a sensitivity of 95.4% and a specificity of 97.5% were obtained. In the multicenter evaluation, a total of 127 events were recorded as embolic signals by at least 1 center. The total number of embolic signals detected by the 6 different centers was 84, 93, 108, 92, 63, and 78. The software set at a confidence threshold of 60% detected 90 events as embolic signals. The mean probability of agreement, including all human experts and the software, was 0.83, and this was higher than that for 2 human experts and lower than that for 4 human experts. The mean values for the 6 human observers were averaged to give P=0.84, which was similar to that of the software. CONCLUSIONS: By using the frequency specificity of the intensity increase occurring with embolic signals, we have developed an automated detection system with a much improved sensitivity. Its performance was equal to that of some human experts and only slightly below the mean performance of a panel of human experts

Algorithms↗
PubMed2006

Automated ribotyping to distinguish the different non Sau/ non Sep staphylococcal emerging pathogens in orthopedic implant infections.

Several species belonging to Staphylococcus genus, other than Staphylococcus aureus and Staphylococcus epidermidis (non Sau/ non Sep species), exhibit increasing abilities as opportunistic pathogens in the colonisation of periprosthetic tissues. Consequently, the availability of means for accurate identification is crucial to assess the pathogenic characteristics and to clarify clinical relevance of the individual species. Here, 146 clinical staphylococcal isolates belonging to non Sau/ non Sep species from prosthesis-associated orthopedic infections were analyzed by conventional enzymatic galleries and by automated ribotyping. Twelve different species were recognised: S. capitis, S. caprae, S. cohnii, S. equorum, S. haemolyticus, S. hominis, S. lugdunensis, S. pasteuri, S. sciuri, S. simulans, S. warneri, S. xylosus. Ribotype identifications were compared with the phenotypes obtained by the Api 20 Staph system and/or ID 32 Staph system. ID 32 Staph profiles were more consistent with ribotyping results than Api Staph profiles. Across the different staphylococcal species investigated, correct identifications with Api Staph were 45%, while with ID 32 Staph they were 59%. It has, however, to be mentioned that ID 32 Staph was mostly applied to discriminate unmatched ribotyping and Api Staph identifications, thus to a subpopulation of strains with ""atypical"" metabolic profile. Automated ribotyping provided a correct identification for 91% of the isolates. These results confirm automated ribotyping as a convenient rapid technique, still subject to improvements, which will accurately and rapidly recognise the newly emerging staphylococcal pathogens in implant-related orthopedic infections.

Automation↗
PubMed2001

HTPS flow cytometry: a novel platform for automated high throughput drug discovery and characterization.

The flow cytometer is unique among biomedical analysis instruments because it makes simultaneous and multiple optical measurements on individual cells or particles at high rates. High throughput flow cytometry represents a potentially important multifactorial approach for screening large combinatorial libraries of compounds. Limiting this approach has been the availability of instrumentation and methods in flow cytometry for automated sample handling on the scale required for drug discovery applications. Here, we describe an automated system in which a novel patented fluidics-based pharmacology platform, the HTPS (High Throughput Pharmacological System), is coupled to a flow cytometer using a recently described plug flow-coupling valve technology. Individual samples are aspirated sequentially from microplate wells and delivered to a flow cytometer for rapid multiparametric analysis. For primary screening to detect and quantify cell fluorescence in endpoint assays, a high-speed no-wash protocol enabled processing of 9-10 cell samples/min from 96-well microplates. In an alternate primary screening format, soluble receptor ligands were sampled from microplate wells at rates of 3-4 samples/minute and successfully assessed for the ability to elicit intracellular calcium responses. Experiments with fluorescent beads validated the accurate automated production by the HTPS of exponential and linear gradients of soluble compounds. This feature enabled rapid (2- to 3-min) characterization of the intracellular calcium dose response of myeloid cells to formyl peptide as well as the quantitative relationship between formyl peptide receptor occupancy and cell response. HTPS flow cytometry thus represents a powerful high throughput multifactorial approach to increase the efficiency with which novel bioresponse-modifying drugs may be identified and characterized.

Automation↗
PubMed2005

Development and application of an automated solution stability assay for drug discovery.

Screening of solution stability provides an early alert on potential liabilities of drug candidates so that strategies can be developed to overcome the challenges. A fully automated solution stability assay has been developed to accelerate traditional manual operation. The assay uses the advanced capabilities of a high-performance liquid chromatography instrument that is present in many pharmaceutical research laboratories. The samples are prepared automatically by a temperature-controlled autosampler. The samples are delivered to the stability matrices, mixed, incubated, and injected at selected time points during the reaction time course. This automated process occurs without operator intervention, thus allowing 96 experiments to be run with 0.5 h of a scientist's time compared to 8 h for the same study when performed manually. Automation not only eliminates the manual operation but also improves accuracy and throughput. The assay protocol has been optimized to achieve homogenous mixing and eliminate carryover. The assay is robust, flexible, and high throughput. It can be used to study stability for a large number of samples under multiple incubation conditions and has a wide range of applications in drug discovery and development, such as screening compound stability in biological assay media, obtaining a stability-pH profile, surveying compound stability in physiological fluids, and performing development forced degradation and excipient compatibility.

Automation↗
PubMed1979

An automated microscope for quantitative cytology combining television image analysis and stage scanning microphotometry.

This paper describes an automated microscope developed for operation in conjunction with the Leyden Television Analysis System. It features automated control of magnification, illumination, movement of scanning stages, and fine focus. These functions are controlled by means of a microcomputer. This enables a flexible design and relieves the supervising computer of simple but time consuming tasks. The combination of an automated microscope and Leyden Television Analysis System provides a powerful tool in quantitative cytological research. The flexible design permits other microscopic functions to be added with relatively little effort.

Computers↗
PubMed2003

Performance of plate-based cytokine flow cytometry with automated data analysis.

BACKGROUND: Cytokine flow cytometry (CFC) provides a multiparameter alternative to ELISPOT assays for rapid quantitation of antigen-specific T cells. To increase the throughput of CFC assays, we have optimized methods for stimulating, staining, and acquiring whole blood or PBMC samples in 96-well or 24-well plates. RESULTS: We have developed a protocol for whole blood stimulation and processing in deep-well 24- or 96-well plates, and fresh or cryopreserved peripheral blood mononuclear cell (PBMC) stimulation and processing in conventional 96-well round-bottom plates. Samples from both HIV-1-seronegative and HIV-1-seropositive donors were tested. We show that the percent response, staining intensity, and cell recovery are comparable to stimulation and processing in tubes using traditional methods. We also show the equivalence of automated gating templates to manual gating for CFC data analysis. CONCLUSION: When combined with flow cytometry analysis using an automated plate loader and an automated analysis algorithm, these plate-based methods provide a higher throughput platform for CFC, as well as reducing operator-induced variability. These factors will be important for processing the numbers of samples required in large clinical trials, and for epitope mapping of patient responses.

Algorithms↗
PubMed2006

Prediction of fluid responsiveness using respiratory variations in left ventricular stroke area by transoesophageal echocardiographic automated border detection in mechanically ventilated patients.

BACKGROUND: Left ventricular stroke area by transoesophageal echocardiographic automated border detection has been shown to be strongly correlated to left ventricular stroke volume. Respiratory variations in left ventricular stroke volume or its surrogates are good predictors of fluid responsiveness in mechanically ventilated patients. We hypothesised that respiratory variations in left ventricular stroke area (DeltaSA) can predict fluid responsiveness. METHODS: Eighteen mechanically ventilated patients undergoing coronary artery bypass grafting were studied immediately after induction of anaesthesia. Stroke area was measured on a beat-to-beat basis using transoesophageal echocardiographic automated border detection. Haemodynamic and echocardiographic data were measured at baseline and after volume expansion induced by a passive leg raising manoeuvre. Responders to passive leg raising manoeuvre were defined as patients presenting a more than 15% increase in cardiac output. RESULTS: Cardiac output increased significantly in response to volume expansion induced by passive leg raising (from 2.16 +/- 0.79 litres per minute to 2.78 +/- 1.08 litres per minute; p < 0.01). DeltaSA decreased significantly in response to volume expansion (from 17% +/- 7% to 8% +/- 6%; p < 0.01). DeltaSA was higher in responders than in non-responders (20% +/- 5% versus 10% +/- 5%; p < 0.01). A cutoff DeltaSA value of 16% allowed fluid responsiveness prediction with a sensitivity of 92% and a specificity of 83%. DeltaSA at baseline was related to the percentage increase in cardiac output in response to volume expansion (r = 0.53, p < 0.01). CONCLUSION: DeltaSA by transoesophageal echocardiographic automated border detection is sensitive to changes in preload, can predict fluid responsiveness, and can quantify the effects of volume expansion on cardiac output. It has potential clinical applications.

Adult↗
PubMed2004

Automated interpretation of protein subcellular location patterns: implications for early cancer detection and assessment.

Fluorescence microscopy is a powerful tool for analyzing the subcellular distributions of proteins, but that power has not been fully utilized because most analysis of those distributions has been done by visual examination. This limitation can be overcome using automated pattern recognition methods widely used in other fields. This article summarizes work demonstrating that automated systems can recognize the patterns of major organelles in both two- and three-dimensional images of cultured cells, and that these systems can distinguish similar patterns better than visual examination. The basis for these systems are sets of Subcellular Location Features that capture the essence of subcellular patterns without being sensitive to the extensive variation that occurs in the size, shape, and orientation of cells in microscope images. These features can also be used to make sensitive, statistical comparisons of the distribution of a protein between two conditions, such as in the presence and absence of a drug. The possible use of automated pattern analysis methods for improving detection of abnormal cells in cancerous or precancerous tissues is also discussed.

Automation↗
PubMed1978

Automation in the animal house.

Whilst appearing attractive, automation must be appraoched with caution. Much time, effort and money is put into curing 'symptoms' without really defining the problem. Too often organizations launch a programme of automation when what they really need is rationalization. Unless you know precisely how much time and effort is currently involved in an operation, you are in grave danger of making costly mistakes in considering automation. A prerequisite is to make sure that your present operation is as productive as it is capable of being.

Animals↗
PubMed2003

Clinical agreement between automated and calculated ultrasound measurements of bladder volume.

Non-invasive urine volume measurement is an important tool in the management of dysfunctional and neuropathic bladders in children. Ultrasound imaging devices have been used for many years for this purpose. An automated scanner (Bladderscan) is now available and has been recommended by a number of authors, but there is conflicting evidence in the literature regarding the accuracy and appropriate clinical application of the device. We aimed to assess the level of clinical agreement between the two methods. 36 urine volume measurements were made on 11 children using both instruments. Although there was a good correlation between the methods (r=0.97), the clinical agreement was poor (limits of agreement +/-77 ml). 13 voided volumes were directly measured and compared with the difference between pre- and post-void ultrasound measurements. The systematic errors were small but the mean absolute errors were 54 ml and 23 ml, respectively, for the automated and ultrasound imaging methods. If used correctly, ultrasound imaging provides more accurate results and can compete with the cost, convenience and ease of use of the automated method. Low cost, highly portable ultrasound imaging devices are now available and should be used in preference to the Bladderscan.

Automation↗
PubMed2004

Automated ribotyping, a rapid typing method for analysis of Erysipelothrix spp. strains.

Automated ribotyping classified 70 Erysipelothrix species strains, previously classified into 14 RAPD patterns and into 63 PFGE patterns, into 27 ribogroups. Twenty-three strains of the 70 analyzed and classified into 13 ribogroups were previously classified into six ribotypes by the traditional ribotyping method. Moreover, automated ribotyping differentiated seven strains that were not differentiated by PFGE. Therefore, automated ribotyping was more sensitive than RAPD and traditional ribotyping, and it might be a useful method for a rapid screening in epidemiological study of strains of this genus, and more accurate results can be obtained when this method is used together with PFGE.

Automation↗
PubMed2002

Fully automated screening systems.

A fully automated system is one of the most valuable tools available for HTS. However, proper sourcing, installation and operation of an automated system requires a thorough inventory of your needs and a strong attention to detail in the implementation and operation. As you could see from the examples, assays can usually be transferred to an automated robotic system with minimum changes. However details must be reviewed to assure that the results will be consistent within a run and as compared to the same assay performed manually on the bench or on workstations. Validation is a crucial element to assure that the integrated system and the individual components are operating within their designated tolerances.

Automation↗
PubMed2000

Automated enzymatic mitochondrial antibody assay for the diagnosis of primary biliary cirrhosis.

Primary biliary cirrhosis is a progressive autoimmune disease that affects middle aged women, resulting in liver cirrhosis. We describe here an automated enzymatic mitochondrial antibody assay adapted for performance on laboratory analysers for the serological diagnosis of primary biliary cirrhosis. This assay detects the characteristic autoantibody directed against the 74kDa E2 subunit of the pyruvate dehydrogenase complex. Analysis of receiver operator characteristic curve data indicated that the automated enzymatic mitochondrial assay procedure discriminated clinically identified patients with primary biliary cirrhosis from normal subjects with a sensitivity of 83% and a specificity of 100%. This method compared favourably against a commercial ELISA method which had a sensitivity of 73% and a specificity of 100%. The automated enzymatic mitochondrial antibody assay is a high throughput assay of use for the routine diagnosis of patients with primary biliary cirrhosis with autoantibodies to the E2 subunit of the pyruvate dehydrogenase complex. The method is of potential value for economical and rapid screening to detect asymptomatic primary biliary cirrhosis in the at-risk segment of the population, namely middle aged women.

Autoantibodies↗