scholarly journals Sample Preparation and Diagnostic Methods for a Variety of Settings: A Comprehensive Review

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5666
Author(s):  
Zach E. Nichols ◽  
Chris D. Geddes

Sample preparation is an essential step for nearly every type of biochemical analysis in use today. Among the most important of these analyses is the diagnosis of diseases, since their treatment may rely greatly on time and, in the case of infectious diseases, containing their spread within a population to prevent outbreaks. To address this, many different methods have been developed for use in the wide variety of settings for which they are needed. In this work, we have reviewed the literature and report on a broad range of methods that have been developed in recent years and their applications to point-of-care (POC), high-throughput screening, and low-resource and traditional clinical settings for diagnosis, including some of those that were developed in response to the coronavirus disease 2019 (COVID-19) pandemic. In addition to covering alternative approaches and improvements to traditional sample preparation techniques such as extractions and separations, techniques that have been developed with focuses on integration with smart devices, laboratory automation, and biosensors are also discussed.

2020 ◽  
Vol 8 (3) ◽  
Author(s):  
Armin Shirvani ◽  
Leila Azimi ◽  
Roxana Mansour Ghanaie ◽  
Masoud Alebouyeh ◽  
Fatemeh Fallah ◽  
...  

: The laboratory diagnosis of SARS-CoV-2 should be done to confirm coronavirus disease 2019 (COVID-19) in suspected patients. Although several diagnostic methods have been developed in this regard, their accuracy for clinical application is not very clear yet. To compare the diagnostic value of laboratory tests for the detection of COVID-19 infection, this study provides an upcoming review of the newly developed detection methods. Sensitivity, specificity, detection limit, and turn-around-time of these methods are compared and challenges for their application in clinical settings are reviewed. PubMed and Google Scholar web sites were used for the systematic search until April 9, 2020 to identify the published studies based on the following keywords: “Detection”, “Coronavirus 2019”, “SARS-CoV-2”, and “Sensitivity”. Out of 526 results, a total of 54 articles, including 46 studies on detection methods, were considered eligible for the review. The results showed that most of the proposed tests focused on molecular methods, while immunological and point-of-care tests were investigated in 13 studies. There were also a few commercial automated methods for the qualitative detection of SARS-CoV-2 in clinical samples, most of which are not examined in the current review, as no data about their sensitivity and specificity were presented. Although the assessment of publication biases showed that 64% sensitivity and nearly 100% specificity for RT-PCR are close to reality, most of the related reports for serological methods are not valid and further studies are needed to confirm their utility in clinical settings. Moreover, the RT-PCR test alone cannot act as a gold standard because of bias in measurements. Therefore, antibody tests and other proposed methods could be used as supplementary diagnostic tests to improve RT-PCR accuracy. Although clinical findings are invaluable, in many cases, they can provide more valuable supportive data than serological tests.


Author(s):  
Earl R. Walter ◽  
Glen H. Bryant

With the development of soft, film forming latexes for use in paints and other coatings applications, it became desirable to develop new methods of sample preparation for latex particle size distribution studies with the electron microscope. Conventional latex sample preparation techniques were inadequate due to the pronounced tendency of these new soft latex particles to distort, flatten and fuse on the substrate when they dried. In order to avoid these complications and obtain electron micrographs of undistorted latex particles of soft resins, a freeze-dry, cold shadowing technique was developed. The method has now been used in our laboratory on a routine basis for several years.The cold shadowing is done in a specially constructed vacuum system, having a conventional mechanical fore pump and oil diffusion pump supplying vacuum. The system incorporates bellows type high vacuum valves to permit a prepump cycle and opening of the shadowing chamber without shutting down the oil diffusion pump. A baffeled sorption trap isolates the shadowing chamber from the pumps.


Author(s):  
P. B. Basham ◽  
H. L. Tsai

The use of transmission electron microscopy (TEM) to support process development of advanced microelectronic devices is often challenged by a large amount of samples submitted from wafer fabrication areas and specific-spot analysis. Improving the TEM sample preparation techniques for a fast turnaround time is critical in order to provide a timely support for customers and improve the utilization of TEM. For the specific-area sample preparation, a technique which can be easily prepared with the least amount of effort is preferred. For these reasons, we have developed several techniques which have greatly facilitated the TEM sample preparation.For specific-area analysis, the use of a copper grid with a small hole is found to be very useful. With this small-hole grid technique, TEM sample preparation can be proceeded by well-established conventional methods. The sample is first polished to the area of interest, which is then carefully positioned inside the hole. This polished side is placed against the grid by epoxy Fig. 1 is an optical image of a TEM cross-section after dimpling to light transmission.


Author(s):  
Mirna Burciaga-Flores ◽  
Marissa Reyes-Galeana ◽  
Tanya A. Camacho-Villegas ◽  
Abel Gutiérrez-Ortega ◽  
Darwin E. Elizondo-Quiroga

Author(s):  
Ng Sea Chooi ◽  
Chor Theam Hock ◽  
Ma Choo Thye ◽  
Khoo Poh Tshin ◽  
Dan Bockelman

Abstract Trends in the packaging of semiconductors are towards miniaturization and high functionality. The package-on-package(PoP) with increasing demands is beneficial in cost and space saving. The main failure mechanisms associated with PoP technology, including open joints and warpage, have created a lot of challenges for Assembly and Failure Analysis (FA). This paper outlines the sample preparation process steps to overcome the challenges to enable successful failure analysis and optical probing.


Author(s):  
Jason H. Lagar ◽  
Rudolf A. Sia

Abstract Most Wafer Level Chip Scale Package (WLCSP) units returned by customers for failure analysis are mounted on PCB modules with an epoxy underfill coating. The biggest challenge in failure analysis is the sample preparation to remove the WLCSP device from the PCB without inducing any mechanical defect. This includes the removal of the underfill material to enable further electrical verification and fault isolation analysis. This paper discusses the evaluations conducted in establishing the WLCSP demounting process and removal of the epoxy underfill coating. Combinations of different sample preparation techniques and physical failure analysis steps were evaluated. The established process enabled the electrical verification, fault isolation and further destructive analysis of WLCSP customer returns mounted on PCB and with an epoxy underfill coating material. This paper will also showcase some actual full failure analysis of WLCSP customer returns where the established process played a vital role in finding the failure mechanism.


Author(s):  
Hyoung H. Kang ◽  
Michael A. Gribelyuk ◽  
Oliver D. Patterson ◽  
Steven B. Herschbein ◽  
Corey Senowitz

Abstract Cross-sectional style transmission electron microscopy (TEM) sample preparation techniques by DualBeam (SEM/FIB) systems are widely used in both laboratory and manufacturing lines with either in-situ or ex-situ lift out methods. By contrast, however, the plan view TEM sample has only been prepared in the laboratory environment, and only after breaking the wafer. This paper introduces a novel methodology for in-line, plan view TEM sample preparation at the 300mm wafer level that does not require breaking the wafer. It also presents the benefit of the technique on electrically short defects. The methodology of thin lamella TEM sample preparation for plan view work in two different tool configurations is also presented. The detailed procedure of thin lamella sample preparation is also described. In-line, full wafer plan view (S)TEM provides a quick turn around solution for defect analysis in the manufacturing line.


2019 ◽  
Vol 26 (11) ◽  
pp. 1946-1959 ◽  
Author(s):  
Le Minh Tu Phan ◽  
Lemma Teshome Tufa ◽  
Hwa-Jung Kim ◽  
Jaebeom Lee ◽  
Tae Jung Park

Background:Tuberculosis (TB), one of the leading causes of death worldwide, is difficult to diagnose based only on signs and symptoms. Methods for TB detection are continuously being researched to design novel effective clinical tools for the diagnosis of TB.Objective:This article reviews the methods to diagnose TB at the latent and active stages and to recognize prospective TB diagnostic methods based on nanomaterials.Methods:The current methods for TB diagnosis were reviewed by evaluating their advantages and disadvantages. Furthermore, the trends in TB detection using nanomaterials were discussed regarding their performance capacity for clinical diagnostic applications.Results:Current methods such as microscopy, culture, and tuberculin skin test are still being employed to diagnose TB, however, a highly sensitive point of care tool without false results is still needed. The utilization of nanomaterials to detect the specific TB biomarkers with high sensitivity and specificity can provide a possible strategy to rapidly diagnose TB. Although it is challenging for nanodiagnostic platforms to be assessed in clinical trials, active TB diagnosis using nanomaterials is highly expected to achieve clinical significance for regular application. In addition, aspects and future directions in developing the high-efficiency tools to diagnose active TB using advanced nanomaterials are expounded.Conclusion:This review suggests that nanomaterials have high potential as rapid, costeffective tools to enhance the diagnostic sensitivity and specificity for the accurate diagnosis, treatment, and prevention of TB. Hence, portable nanobiosensors can be alternative effective tests to be exploited globally after clinical trial execution.


2020 ◽  
Vol 16 ◽  
Author(s):  
Mustafa Çelebier ◽  
Merve Nenni

Background: Metabolomics has gained importance in clinical applications over the last decade. Metabolomics studies are significant because the systemic metabolome is directly affected by disease conditions. Metabolome-based biomarkers are actively being developed for early diagnosis and to indicate the stage of specific diseases. Additionally, understanding the effect of an intervention on a living organism at the molecular level is a crucial strategy for understanding novel or unexpected biological processes. Results: The simultaneous improvements in advanced analytical techniques, sample preparation techniques, computer technology, and databank contents has enabled more valuable scientific information to be gained from metabolomics than ever before. With over 15,000 known endogenous metabolites, there is no single analytical technique capable of analyzing the whole metabolome. However, capillary electrophoresis-mass spectrometry (CE-MS) is a unique technique used to analyze an important portion of metabolites not accessible by liquid chromatography or gas chromatography techniques. The analytical capability of CE, combined with recent sample preparation techniques focused on extracting polar-ionic compounds, make CE-MS a perfect technique for metabolomic studies. Conclusion: Here, previous reviews of CE-MS based metabolomics are evaluated to highlight recent improvements in this technique. Specifically, we review papers from the last two years (2018 and 2019) on CE-MS based metabolomics. The current situation and the challenges facing metabolomic studies are discussed to reveal the high potential of CE-MS for further studies, especially in biomarker development studies.


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