Handling Of Biological Samples Research Articles

Effectiveness of TRIzol in Inactivating Animal Pathogens

Introduction: Safe handling of biological samples sourced from wild ecosystems is a pressing concern for scientists in disparate fields, including ecology and evolution, OneHealth initiatives, bioresources, geography, veterinary medicine, conservation, and many others. This is especially relevant given the growing global research community and collaborative networks that often span international borders. Treatments to inactivate potential pathogens of concern during transportation and analysis of biospecimens while preserving molecular structures of interest are necessary. Objective: We provide a detailed resource on the effectiveness and limitations of TRIzol™ Reagent, a product commonly used in molecular biology to inactivate bacterial and viral pathogens found in wild animals. Methods: By literature review, we evaluate the mode of action of TRIzol Reagent and its main components on bacterial and viral structures. We also synthesize peer-reviewed literature on the effectiveness of TRIzol in inactivating a broad range of infectious bacteria and viruses. Key Findings: TRIzol Reagent inactivation is based on phenol, chaotropic salts, and sodium acetate. We find evidence of widespread efficacy in deactivating bacteria and a broad range of enveloped viruses. The efficacy against a subset of potential pathogens, including some nonenveloped viruses, remains uncertain. Conclusion: Available evidence suggests that TRIzol Reagent is effective in inactivating a broad spectrum of bacteria and viruses from cells, tissues, and liquids in biological samples when the matrices are exposed to at least 10 min at room temperature to the reagent. We highlight areas that require additional research and discuss implications for laboratory protocols.

Design of a Novel Magnetically Actuated Biaxial Robot With Compact Structure and Easy Operation

This paper presents the design, fabrication, and testing of a novel magnetically actuated biaxial robot with compact structure and easy operation. For the first time, the untethered robot enables grasping, rotating, and transporting operations of the target object by integrating magnetic torque and force driving. The grasping and rotating operations are realized via the magnetic torque produced by custom-built electromagnetic coils. The transporting process is implemented by the magnetic force created by permanent magnets carried on an external manipulator. Analytical models are established for studying the working principle. Optimization of the robot's structural parameters is carried out by performing a finite-element analysis simulation to achieve the expected performance. To characterize the actual performance, a magnetically actuated biaxial robot prototype is fabricated, and experimental tests are conducted. For demonstration, a zebrafish embryo has been dexterously manipulated by the proposed robot operating in a Petri dish filled with pure water. The results indicate that the reported robot can be used in the practical application of biological sample handling.

Organ-on-a-chip and 3D printing as preclinical models for medical research and practice

In recent years, ever-increasing scientific knowledge and modern high-tech advancements in micro- and nano-scales fabrication technologies have impacted significantly on various scientific fields. A micro-level approach so-called “microfluidic technology” has rapidly evolved as a powerful tool for numerous applications with special reference to bioengineering and biomedical engineering research. Therefore, a transformative effect has been felt, for instance, in biological sample handling, analyte sensing cell-based assay, tissue engineering, molecular diagnostics, and drug screening, etc. Besides such huge multi-functional potentialities, microfluidic technology also offers the opportunity to mimic different organs to address the complexity of animal-based testing models effectively. The combination of fluid physics along with three-dimensional (3-D) cell compartmentalization has sustained popularity as organ-on-a-chip. In this context, simple humanoid model systems which are important for a wide range of research fields rely on the development of a microfluidic system. Development of microfluidic-based technology bridges the gap between in vitro and in vivo models offering new approaches to research in medicine, biology, and pharmacology, among others.

Bioethical Education and Standardization of Sample Handling Procedures in Raman Spectroscopy Research Studies Involving Human Subjects

Novelty: Raman spectroscopy is extensively explored for the disease diagnostics in recent decade. There is limited literature available concerning the standardization of sample handling procedures in Raman spectroscopy research studies involving human subjects. In fact, the present study provided guidance for a harmonize data to conduct Raman spectroscopy research studies involving human subjects for better outcomes based on ethical principles. Objectives: Globally, multi-disciplinary research is conducted for better outcomes in the welfare of humankind. The present study was aimed to provide basic guidance of bioethical education for research students conducting research involving human subjects. Further, the present study was attempted to standardize sample handling procedure in Raman spectroscopy research involving human subjects for better outcomes in disease diagnosis. Materials and methods: We have provided bioethical recommendations based on fundamental ethics codes. The standardization of sample handling procedure was developed using human surgical samples of breast cancer patients. Findings: The researcher should justify the inclusion and exclusion criteria for biological samples to conduct the scientifically valid research study. Research studies involving biological samples shall develop research protocol for the preparation and handling of biological samples. The results of present study suggest that fresh clinically unprocessed tissue samples are superior to conduct research studies involving Raman spectroscopy for disease progression. In case the research is not concerned with positive net benefit for human participants with diagnosis of communicable diseases, the researcher shall exclude these patients from the research study. Informed consent, preferably in writing, has to be obtained from participants in a language in that participant comprehend. Conclusion: The present study described primary bioethical education and standardization techniques for research students to plan and conduct Raman spectroscopy research studies involving human biological materials. Keywords: Raman spectroscopy; Bioethics; Cancer; Diagnosis; Spectrum

An Update on Sphingolipidomics: Is Something Still Missing? Some Considerations on the Analysis of Complex Sphingolipids and Free-Sphingoid Bases in Plasma and Red Blood Cells.

The main concerns in targeted “sphingolipidomics” are the extraction and proper handling of biological samples to avoid interferences and achieve a quantitative yield well representing all the sphingolipids in the matrix. Our work aimed to compare different pre-analytical procedures and to evaluate a derivatization step for sphingoid bases quantification, to avoid interferences and improve sensitivity. We tested four protocols for the extraction of sphingolipids from human plasma, at different temperatures and durations, and two derivatization procedures for the conversion of sphingoid bases into phenylthiourea derivatives. Different columns and LC-MS/MS chromatographic conditions were also tested. The protocol that worked better for sphingolipids analysis involved a single-phase extraction in methanol/chloroform mixture (2:1, v/v) for 1 h at 38 °C, followed by a 2 h alkaline methanolysis at 38 °C, for the suppression of phospholipids signals. The derivatization of sphingoid bases promotes the sensibility of non-phosphorylated species but we proved that it is not superior to a careful choice of the appropriate column and a full-length elution gradient. Our procedure was eventually validated by analyzing plasma and erythrocyte samples of 20 volunteers. While both extraction and methanolysis are pivotal steps, our final consideration is to analyze sphingolipids and sphingoid bases under different chromatographic conditions, minding the interferences.

POSITIVE IMPACT OF AN AUTOMATED PRE-ANALYTICAL & POST-ANALYTICAL WORKFLOW SYSTEM IN A TERTIARY HIGH-VOLUME REFERRAL CLINICAL LABORATORY

Context: Handling of biological samples in a laboratory is labour intensive complex process and automation has become a necessity for optimizing health care costs, reduce medical errors and to aid in safety of healthcare workers. Biological Sample handling in the sample reception area involves sample tube de-capping for ready processing, sorting section-wise, scanning the sample to track its progress, distribution to various analysers and archival for storage. The aim of the present study is to evaluate the positive effects of an automatic pr Objective: e analytical automation in our clinical laboratory workow. We recently installed Beckman Automate 2550 analyser for our wor Design: kow pre & post analytical automation.This preanalytical unit processes blood specimens through automated specimen sorting, centrifugation, de-capping, labelling, aliquoting, and placement of the processed specimen in the analytical rack. We analysed the system by processing samples to test the salient features of this system. Turnaround time with increase in volume of tests with no additional manpower was analysed pre & post automation. The turnaround ti Results: me (TAT) of various laboratory processes demonstrated a signicant improvement. The number of errors experienced in tube sorting with manual processing, sorting mislabelled tubes, unlabelled tubes, specimen lost, wrong destination entered for tubes and tube mismatch was decreased post-implementation of the system. Also, increased workload was handled by the sorter efciently. Conclusions: Reduction time in pre analytical processing and sorting of samples led to signicant improvements in TAT and specimen processing after automation. The manual errors & manhours associated with sorting, labelling, aliquoting the blood samples also reduced. These results conclude that automated sample sorting improves specimen accessioning and processing workow.

Guía de práctica clínica para la bioseguridad en toma de muestras en México

Background. The collection of biological samples has several phases: pre-analytical, analytical and post-analytical. Every time a biological sample collection procedure is performed there are risks of exposure to infectious agents that require applying well-established biosafety protocols. Objective. In order to promote biosafety in the pre-analytical phase of biological samples and standardize its protocol, the authors developed Guía de práctica clínica para la bioseguridad en toma de muestras en México (Clinical Practice Guide for Biosafety in Sample Taking in Mexico), including recommendations for patient and worker safety. Methodology. An interdisciplinary group of health worker specialists involved in taking samples met. Bibliographic searches were carried out. The authors selected the articles and published guidelines, and adapted the recommendations to our country reality. Results. Biosafety procedures were developed for sampling, including essential actions for patient safety, reducing the risk of infections associated with health care, biosafety for the health worker, and the use of antiseptics. Conclusions. There is no official standard for preventive actions in reducing risks associated with the handling of biological samples. This Guía can contribute, through adequate dissemination, to standardize criteria and protocols.

Evaluation of henipavirus chemical inactivation methods for the safe removal of samples from the high-containment PC4 laboratory

Henipaviruses, Hendra (HeV) and Nipah (NiV), are highly pathogenic zoonotic agents that pose a serious health risk to human life, and as such are restricted to physical containment 4 (PC4) laboratories. For further analysis of virus-infected biological specimens, it is necessary to ensure absolute inactivation of any infectious virus present before removal from the PC4 laboratory. To evaluate the inactivation of HeV and NiV within infected samples, two chemical inactivation methods were assessed. Henipavirus-infected cell monolayers treated with 4 % paraformaldehyde (PFA) showed the complete inactivation of infectious virus, with an inactivation period of 15 min resulting in more than 8-log decrease in infectious titre. NiV-infected tissue samples treated with 10 % neutral-buffered formalin (NBF) showed a complete reduction of infectious virus in 7/8 ferret organs incubated for 24 h, with the remaining tissue demonstrating complete virus inactivation after 48 h. The chemical inactivation methods described herein evaluated two simple methods of henipavirus inactivation, resulting in the complete inactivation of infectious virus – an essential requirement for the safe removal and handling of biological samples from the PC4 laboratory.

A high throughput lipidomics method and its application in atrial fibrillation based on 96-well plate pretreatment and liquid chromatography-mass spectrometry

Successful applications of lipidomics in clinic need study large-scale samples, and the bottlenecks are in throughput and robustness of the lipid analytical method. Here, we report an untargeted lipidomics method by combining high throughput pretreatment in the 96-well plate with ultra-high performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry. The developed method was validated to have satisfactory analytical characteristics in terms of linearity, repeatability and extraction recovery. It can be used to handle 96 samples simultaneously in 25 min and detect 441 lipids in plasma sample. Storage stability investigation on lipid extracts provided an operable procedure for large-scale sample analysis and demonstrated most lipids were stable in autosampler at 10 °C within 36 h and at -80 °C within 72 h after the pretreatment. To prove the usefulness, the method was employed to investigate abnormal plasma lipidome related to atrial fibrillation. A biomarker panel with the area under the curve (AUC) values of 0.831 and 0.745 was achieved in the discovery and external validation sets, respectively. These results showed that the developed method is applicable for large-scale biological sample handling and lipid analysis of plasma.

Mechanisms of Plasma-Seed Treatments as a Potential Seed Processing Technology

Plasma treatments are currently being assessed as a seed processing technology for agricultural purposes where seeds are typically subjected to pre-sowing treatments to improve the likelihood of timely and uniform germination. The aim of this review is to summarize the hypotheses and present the evidence to date of how plasma treatments affect seeds, considering that there is difficulty in standardizing the methodology in this interdisciplinary field given the plethora of variables in the experimental setup of the plasma device and handling of biological samples. The ever increasing interest for plasma agriculture drives the need for a review dedicated to seeds, which is understandable to an interdisciplinary audience of biologists and plasma physicists. Seeds are the first step of the agricultural cycle and at this stage, the plant can be given the highest probability of establishment, despite environmental conditions, to exploit the genetic potential of the seed. Furthermore, seedlings seem to be too sensitive to the oxidation of plasma and therefore, seeds seem to be the ideal target. This review intentionally does not include seed disinfection and sterilization due to already existing reviews. Instead, a summary of the mechanisms of how plasma may be affecting the seed and its germination and developmental properties will be provided and discussed.

Extracellular Vesicles Analysis in the COVID-19 Era: Insights on Serum Inactivation Protocols towards Downstream Isolation and Analysis.

Since the outbreak of the COVID-19 crisis, the handling of biological samples from confirmed or suspected SARS-CoV-2-positive individuals demanded the use of inactivation protocols to ensure laboratory operators’ safety. While not standardized, these practices can be roughly divided into two categories, namely heat inactivation and solvent-detergent treatments. These routine procedures should also apply to samples intended for Extracellular Vesicles (EVs) analysis. Assessing the impact of virus-inactivating pre-treatments is therefore of pivotal importance, given the well-known variability introduced by different pre-analytical steps on downstream EVs isolation and analysis. Arguably, shared guidelines on inactivation protocols tailored to best address EVs-specific requirements will be needed among the analytical community, yet deep investigations in this direction have not yet been reported. We here provide insights into SARS-CoV-2 inactivation practices to be adopted prior to serum EVs analysis by comparing solvent/detergent treatment vs. heat inactivation. Our analysis entails the evaluation of EVs recovery and purity along with biochemical, biophysical and biomolecular profiling by means of a set of complementary analytical techniques: Nanoparticle Tracking Analysis, Western Blotting, Atomic Force Microscopy, miRNA content (digital droplet PCR) and tetraspanin assessment by microarrays. Our data suggest an increase in ultracentrifugation (UC) recovery following heat treatment; however, it is accompanied by a marked enrichment in EVs-associated contaminants. On the other hand, solvent/detergent treatment is promising for small EVs (<150 nm range), yet a depletion of larger vesicular entities was detected. This work represents a first step towards the identification of optimal serum inactivation protocols targeted to EVs analysis.

Assessment of inactivation procedures for SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), presents a challenge to laboratorians and healthcare workers around the world. Handling of biological samples from individuals infected with the SARS-CoV-2 virus requires strict biosafety measures. Within the laboratory, non-propagative work with samples containing the virus requires, at minimum, Biosafety Level-2 (BSL-2) techniques and facilities. Therefore, handling of SARS-CoV-2 samples remains a major concern in areas and conditions where biosafety for specimen handling is difficult to maintain, such as in rural laboratories or austere field testing sites. Inactivation through physical or chemical means can reduce the risk of handling live virus and increase testing ability especially in low-resource settings due to easier and faster sample processing. Herein we assess several chemical and physical inactivation techniques employed against SARS-CoV-2 isolates from Cambodia. This data demonstrates that all chemical (AVL, inactivating sample buffer and formaldehyde) and heat-treatment (56 and 98 °C) methods tested completely inactivated viral loads of up to 5 log10.

Design of a parallel robot with additively manufactured flexure hinges for a cryogenic work environment

Automation is ubiquitous in today’s industrial landscape and is finding its way into more and more highly specialised applications - also in the field of cryopreservation. The extreme work conditions in cryobanks place exceptionally high demands on the mechanical and electronic components used. The preservation and storage of biological samples take place at temperatures between -130 °C and -196 °C using liquid nitrogen as a cooling medium. The bearings and joints used in industrial parallel kinematic robots (for example, ball bearings or Cardan joints) jam at these ambient parameters and are unsuitable for an application within a cryobank. We, therefore, develop methods and technologies to enable fully automated handling of biological samples under cryogenic working conditions. The basis for this is a parallel kinematic robot structure that allows the drives to be placed outside the cold environment. In contrast, the rest of the robot structure can be actuated in a cryogenic container.In this context, the passive joints for this parallel robot are designed as additively manufactured monolithic flexure hinges. This paper presents the design, simulation, and construction of the parallel robot and focuses on the flexure hinges fabricated using the selective laser melting process (SLM). We describe the design of the flexure hinges, their intended use in the robot, and the experimental setup used for their validation. We also compare the operating parameters recorded in experiments (such as bending angle, bending moment) with the data obtained in finite element method simulations (FEM). In addition, we describe the geometric constraints and deviations of the manufactured joints due to the manufacturing process.

The Anatomic Pathology laboratory adjustments in the era of COVID-19 pandemic: The experience of a laboratory in a Portuguese central hospital

The coronavirus disease 2019 (COVID-19) pandemic has dramatically changed the world over the past weeks, with already 8,25 million infections and 445,000 deaths worldwide, leading to an unprecedented international global effort to contain the virus and prevent its spread. The emergence of novel respiratory viruses such as the SARS-CoV-2 creates dramatic challenges to the healthcare services, including surgical pathology laboratories, despite their extensive daily experience in dealing with biological and chemical hazards. Here, we cover important aspects on the knowledge on COVID-19 gathered during the first six months of the pandemic and address relevant issues on human biological sample handling in the Anatomic Pathology laboratory in the context of COVID-19 global threat. In addition, we detail our strategy to minimize the risk of contamination upon exposure to the different biological products received in the laboratory, which can be of general interest to other laboratories worldwide. Our approach has enabled a safe work environment for laboratory staff, while ensuring the maintenance of high quality standards of the work performed. In times of uncertainty and given the lack of specific guidelines directed at Anatomic Pathology services to better deal with the global COVID-19 public-health emergency, it is essential to share with the community rigorous methodologies that will enable us to better cope with probable novel waves of COVID-19 infection and other viruses that will possibly arise in the near future.

Strengthening of Molecular Diagnosis of SARS-CoV-2 / COVID-19 with a Special Focus on India

Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2), a novel coronavirus initially reported in Wuhan, China, is the causative agent of coronavirus disease (COVID-19) pandemic. Symptoms of the disease comprise of fever, tiredness, dry cough, aches and pains, nasal congestion, runny nose, sore throat, diarrhoea and pneumonia at the late stage. SARS-CoV-2 has severely crippled the healthcare system and has caused huge economic losses. Following the outbreak, the SARS-CoV-2 was recognized timely and its genome was sequenced, leading to the development of real-time polymerase chain reaction assays for its detection in clinical samples collected from suspected cases. The management of the pandemic is limited by a number of misconceptions and insufficient information about laboratory testing for SARS-CoV-2 to confirm the disease. This includes a lack of awareness about procedures for the collection, transport, testing, and handling of biological samples for COVID diagnosis. This article provides an overview of the current laboratory diagnostic methods with a purpose to provide information and guidance to laboratories, stakeholders, broader community and especially public health professionals involved in laboratory testing for SARS-CoV-2.

Pre-formulation investigations for establishing a protocol for treosulfan handling and activation

Introduction: Treosulfan is an alkylating agent that is used for the treatment of ovarian cancer and for conditioning prior to stem cell transplantation. It is a prodrug that is activated non-enzymatically to two active epoxides.Objectives: To optimize a protocol for both in vivo samples handling and in vitro drug preparation. Treosulfan stability was tested in biological fluids at different conditions as well as for its cytotoxicity on cell lines.Results: Plasma samples can be safely frozen for a short period up to 8 h, however; for longer periods, samples should be acidified. Urine samples and cell culture media can be safely frozen regardless their pH. For in vitro investigations, incubation of treosulfan at 37 °C for 24 h activated 100% of the drug. Whole blood acidification should be avoided for the risk of hemolysis. Finally; treosulfan cytotoxicity on HL-60 cells has increased following pre-incubation for 24 h at 37 °C compared to K562 cell line.Conclusion: The stability profiling of treosulfan provided a valuable reference for handling of biological samples for both in vivo and in vitro studies. These results can be utilized for further investigations concerning the drug kinetics and dynamics in addition to the development of new pharmaceutical formulations.

Organs-on-a-Chip Module: A Review from the Development and Applications Perspective.

In recent years, ever-increasing scientific knowledge and modern high-tech advancements in micro- and nano-scales fabrication technologies have impacted significantly on various scientific fields. A micro-level approach so-called “microfluidic technology” has rapidly evolved as a powerful tool for numerous applications with special reference to bioengineering and biomedical engineering research. Therefore, a transformative effect has been felt, for instance, in biological sample handling, analyte sensing cell-based assay, tissue engineering, molecular diagnostics, and drug screening, etc. Besides such huge multi-functional potentialities, microfluidic technology also offers the opportunity to mimic different organs to address the complexity of animal-based testing models effectively. The combination of fluid physics along with three-dimensional (3-D) cell compartmentalization has sustained popularity as organ-on-a-chip. In this context, simple humanoid model systems which are important for a wide range of research fields rely on the development of a microfluidic system. The basic idea is to provide an artificial testing subject that resembles the human body in every aspect. For instance, drug testing in the pharma industry is crucial to assure proper function. Development of microfluidic-based technology bridges the gap between in vitro and in vivo models offering new approaches to research in medicine, biology, and pharmacology, among others. This is also because microfluidic-based 3-D niche has enormous potential to accommodate cells/tissues to create a physiologically relevant environment, thus, bridge/fill in the gap between extensively studied animal models and human-based clinical trials. This review highlights principles, fabrication techniques, and recent progress of organs-on-chip research. Herein, we also point out some opportunities for microfluidic technology in the future research which is still infancy to accurately design, address and mimic the in vivo niche.

Developing a MEMS Device with Built-in Microfluidics for Biophysical Single Cell Characterization.

This study combines the high-throughput capabilities of microfluidics with the sensitive measurements of microelectromechanical systems (MEMS) technology to perform biophysical characterization of circulating cells for diagnostic purposes. The proposed device includes a built-in microchannel that is probed by two opposing tips performing compression and sensing separately. Mechanical displacement of the compressing tip (up to a maximum of 14 µm) and the sensing tip (with a quality factor of 8.9) are provided by two separate comb-drive actuators, and sensing is performed with a capacitive displacement sensor. The device is designed and developed for simultaneous electrical and mechanical measurements. As the device is capable of exchanging the liquid inside the channel, different solutions were tested consecutively. The performance of the device was evaluated by introducing varying concentrations of glucose (from 0.55 mM (0.1%) to 55.5 mM (10%)) and NaCl (from 0.1 mM to 10 mM) solutions in the microchannel and by monitoring changes in the mechanical and electrical properties. Moreover, we demonstrated biological sample handling by capturing single cancer cells. These results show three important capabilities of the proposed device: mechanical measurements, electrical measurements, and biological sample handling. Combined in one device, these features allow for high-throughput multi-parameter characterization of single cells.

Integrating printed microfluidics with silicon photomultipliers for miniaturised and highly sensitive ATP bioluminescence detection

Bioluminescence has been widely used for important biosensing applications such as the measurement of adenosine triphosphate (ATP), the energy unit in biological systems and an indicator of vital processes. The current technology for detection is mainly based on large equipment such as readers and imaging systems, which require intensive and time-consuming procedures. A miniaturised bioluminescence sensing system, which would allow sensitive and continuous monitoring of ATP, with an integrated and low-cost disposable microfluidic chamber for handling of biological samples, is highly desirable. Here, we report the design, fabrication and testing of 3D printed microfluidics chips coupled with silicon photomultipliers (SiPMs) for high sensitive real-time ATP detection. The 3D microfluidic chip reduces reactant consumption and facilitates solution delivery close to the SiPM to increase the detection efficiency. Our system detects ATP with a limit of detection (LoD) of 8nM and an analytical dynamic range between 15nM and 1µM, showing a stability error of 3%, and a reproducibility error below of 20%. We demonstrate the dynamic monitoring of ATP in a continuous-flow system exhibiting a fast response time, ~4s, and a full recovery to the baseline level within 17s. Moreover, the SiPM-based bioluminescence sensing system shows a similar analytical dynamic range for ATP detection to that of a full-size PerkinElmer laboratory luminescence reader.

3D FEM analyses of the ultrasonic transducer for controlled nanowire rotary driving

Controlled rotary driving of single nano objects is an important technology in the assembling of nano structures, handling of biological samples, nano measurement, etc. However, there have been little analyses on the ultrasonic transducers for the nano rotary driving, which makes the transducer’s optimization impossible. In this work, vibration characteristics of the ultrasonic transducer for rotary driving of single nanowires, which has been proposed by the authors’ group, are analyzed by the 3D finite element method (FEM), and some useful guidelines for designing the transducer are achieved. It is found that the working point still exists when the commonly used metal materials in ultrasonic transducers are used as the vibration transmission strip, and when the vibration transmission strip’s size changes. It is also found that the direction of the elliptical motion of the micro manipulating probe’s tip may be reversed by changing the size of the vibration transmission strip properly. In addition, to ensure the performance consistency of the device, the micro manipulating probe’s length Lm or driving frequency should be designed to avoid the resonance of the micro manipulating probe.