High Sensitivity MEMS Biosensor for Monitoring Cell Attachment

2012 ◽  
Author(s):  
Fei Liu ◽  
Fang Li ◽  
David C. Spray ◽  
Anis Nurashikin Nordin ◽  
Ioana Voiculescu
Keyword(s):  
Resonant Frequency ◽  
Cell Attachment ◽  
High Sensitivity ◽  
Live Cells ◽  
Seeding Density ◽  
Impedance Sensing ◽  
Aortic Endothelial Cells ◽  
Frequency Measurements ◽  
Cell Substrate ◽  
Time Required

This paper presents the fabrication and testing of a novel microelectromechanical (MEMS) biosensor based on live cells. The biosensor combines two biosensing techniques; resonant frequency measurements and electric cell-substrate impedance sensing (ECIS) on a single device. The sensor is based on the innovative placement of the working microelectrode for ECIS technique as the upper electrode of a quartz crystal microbalance (QCM) resonator. This hybrid biosensor was tested with bovine aortic endothelial cells with different seeding densities. The cell attachment and spreading was monitored with both sensors; the QCM and the ECIS technique. After the cells form a monolayer the values of the impedance and resonant frequency measurements are constant. The optimal cell seeding density with minimal time required to attach and form a monolayer was observed to be 1.5×104 cells/cm2. This biosensor monitors the cells attachment and viability and could be used for screening toxicants in drinking water.

High-Sensitivity MEMS Resonant Biosensor for Monitoring Water Toxicity

2017 ◽  
Author(s):  
Kun-Lin Lee ◽  
Simon Ng ◽  
Fang Li ◽  
Ioana Voiculescu
Keyword(s):  
Resonant Frequency ◽  
Quartz Crystal ◽  
High Sensitivity ◽  
Live Cells ◽  
Toxicity Tests ◽  
Piezoelectric Resonator ◽  
Sensitivity Testing ◽  
Water Toxicity ◽  
Water Based ◽  
Trout Gill

This paper presents the use of a piezoelectric resonator, which can be applied to investigate live cells activity in water-based toxic solution. We perform toxicity tests using commercial quartz crystal microbalance (QCM). The QCM used in this research has the resonant frequency of 10 MHz and consists in an AT-cut crystal with gold electrodes on both sides. This QCM was transformed into a functional biosensor by integrating with polydimethylsiloxane (PDMS) culturing chambers. Rainbow trout gill epithelial cells (RTgill-W1) were cultured on the resonators as sensorial layer. The fluctuation of the resonant frequency, due to the change of cell morphology and adhesion, is an indicator of water toxicity. The shift of resonant frequency will provide information about the cells viability after exposure to toxicants. Experiment setup, fabrication process, and sensor sensitivity testing are addressed. The toxicity result shows distinct responses for different ammonia concentrations.

scholarly journals Nano and Microsensors for Mammalian Cell Studies

Micromachines ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 439 ◽  
Author(s):  
Ioana Voiculescu ◽  
Masaya Toda ◽  
Naoki Inomata ◽  
Takahito Ono ◽  
Fang Li
Keyword(s):  
Resonant Frequency ◽  
Cantilever Beam ◽  
Mammalian Cell ◽  
Temperature Sensor ◽  
Mammalian Cells ◽  
High Sensitivity ◽  
Biological Applications ◽  
Impedance Sensing ◽  
Frequency Regime ◽  
Response To Temperature

This review presents several sensors with dimensions at the nano- and micro-scale used for biological applications. Two types of cantilever beams employed as highly sensitive temperature sensors with biological applications will be presented. One type of cantilever beam is fabricated from composite materials and is operated in the deflection mode. In order to achieve the high sensitivity required for detection of heat generated by a single mammalian cell, the cantilever beam temperature sensor presented in this review was microprocessed with a length at the microscale and a thickness in the nanoscale dimension. The second type of cantilever beam presented in this review was operated in the resonant frequency regime. The working principle of the vibrating cantilever beam temperature sensor is based on shifts in resonant frequency in response to temperature variations generated by mammalian cells. Besides the cantilever beam biosensors, two biosensors based on the electric cell-substrate impedance sensing (ECIS) used to monitor mammalian cells attachment and viability will be presented in this review. These ECIS sensors have dimensions at the microscale, with the gold films used for electrodes having thickness at the nanoscale. These micro/nano biosensors and their mammalian cell applications presented in the review demonstrates the diversity of the biosensor technology and applications.

Multiparametric MEMS Biosensors With Integrated Impedance Spectroscopy and Gravimetric Measurements for Water Toxicity Sensing

2013 ◽  
Author(s):  
Fei Liu ◽  
Fang Li ◽  
Ali Khademhosseini ◽  
Ioana Voiculescu
Keyword(s):  
Resonant Frequency ◽  
Mammalian Cells ◽  
False Positive Rate ◽  
Cell Monolayer ◽  
Ammonia Solution ◽  
Toxicity Tests ◽  
Single Chip ◽  
Impedance Sensing ◽  
Aortic Endothelial Cells ◽  
Positive Rate

This paper presents the design, fabrication and characterization of a novel multiparametric microelectromechanical (MEMS) biosensor based on live mammalian cells with capabilities of sensing the toxicity of field water with minimized false-positive rate. This biosensor combines two biosensing techniques, resonant frequency measurements and electric cell-substrate impedance sensing (ECIS) on a single chip. The sensor is based on the innovative placement of the working microelectrode for ECIS technique as the upper electrode of a quartz crystal microbalance (QCM) resonator. This multiparametric biosensor was characterized with bovine aortic endothelial cells (BAECs). Toxicity tests to study BAECs responsiveness to health-threatening concentrations of ammonia in de-ionized water as a toxicant model will also be presented. The increase of the resonant frequency and decrease of impedance of the biosensor indicated the detachment of cells as a result of toxicant stimulation of ammonia solution. These gravimetric and impedimetric measurements on the same cell monolayer demonstrate that the multiparametric biosensor is able to perform two types of measurements simultaneously and this sensor can successfully be tested with drinking water containing toxicants.

scholarly journals Fluorescent Probes for Live Cell Thiol Detection

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3575
Author(s):  
Shenggang Wang ◽  
Yue Huang ◽  
Xiangming Guan
Keyword(s):  
Fluorescent Probes ◽  
Biological System ◽  
High Sensitivity ◽  
Intracellular Distribution ◽  
Live Cell ◽  
Live Cells ◽  
High Demand ◽  
Non Invasive

Thiols play vital and irreplaceable roles in the biological system. Abnormality of thiol levels has been linked with various diseases and biological disorders. Thiols are known to distribute unevenly and change dynamically in the biological system. Methods that can determine thiols’ concentration and distribution in live cells are in high demand. In the last two decades, fluorescent probes have emerged as a powerful tool for achieving that goal for the simplicity, high sensitivity, and capability of visualizing the analytes in live cells in a non-invasive way. They also enable the determination of intracellular distribution and dynamitic movement of thiols in the intact native environments. This review focuses on some of the major strategies/mechanisms being used for detecting GSH, Cys/Hcy, and other thiols in live cells via fluorescent probes, and how they are applied at the cellular and subcellular levels. The sensing mechanisms (for GSH and Cys/Hcy) and bio-applications of the probes are illustrated followed by a summary of probes for selectively detecting cellular and subcellular thiols.

scholarly journals Optimal Scheduling for Laboratory Automation of Life Science Experiments with Time Constraints

2021 ◽  
pp. 247263032110217
Author(s):  
Takeshi D. Itoh ◽  
Takaaki Horinouchi ◽  
Hiroki Uchida ◽  
Koichi Takahashi ◽  
Haruka Ozaki
Keyword(s):  
Scheduling Algorithms ◽  
Mixed Integer ◽  
Time Constraints ◽  
Live Cells ◽  
Laboratory Automation ◽  
Simulation Based Design ◽  
Simulation Based ◽  
Optimal Allocations ◽  
Scheduling Method ◽  
Time Required

In automated laboratories consisting of multiple different types of instruments, scheduling algorithms are useful for determining the optimal allocations of instruments to minimize the time required to complete experimental procedures. However, previous studies on scheduling algorithms for laboratory automation have not emphasized the time constraints by mutual boundaries (TCMBs) among operations, which is important in procedures involving live cells or unstable biomolecules. Here, we define the “scheduling for laboratory automation in biology” (S-LAB) problem as a scheduling problem for automated laboratories in which operations with TCMBs are performed by multiple different instruments. We formulate an S-LAB problem as a mixed-integer programming (MIP) problem and propose a scheduling method using the branch-and-bound algorithm. Simulations show that our method can find the optimal schedules of S-LAB problems that minimize overall execution time while satisfying the TCMBs. Furthermore, we propose the use of our scheduling method for the simulation-based design of job definitions and laboratory configurations.

scholarly journals Complex Permittivity Characterization of Liquid Samples Based on a Split Ring Resonator (SRR)

Sensors ◽  
2021 ◽  
Vol 21 (10) ◽  
pp. 3385
Author(s):  
Jialu Ma ◽  
Jingchao Tang ◽  
Kaicheng Wang ◽  
Lianghao Guo ◽  
Yubin Gong ◽  
...  
Keyword(s):  
Resonant Frequency ◽  
Complex Permittivity ◽  
Ring Resonator ◽  
High Sensitivity ◽  
Split Ring Resonator ◽  
Debye Model ◽  
Split Ring ◽  
Liquid Samples ◽  
Microwave Sensor

A complex permittivity characterization method for liquid samples has been proposed. The measurement is carried out based on a self-designed microwave sensor with a split ring resonator (SRR), the unload resonant frequency of which is 5.05 GHz. The liquid samples in capillary are placed in the resonant zone of the fabricated senor for high sensitivity measurement. The frequency shift of 58.7 MHz is achieved when the capillary is filled with ethanol, corresponding a sensitivity of 97.46 MHz/μL. The complex permittivity of methanol, ethanol, isopropanol (IPA) and deionized water at the resonant frequency are measured and calibrated by the first order Debye model. Then, the complex permittivity of different concentrations of aqueous solutions of these materials are measured by using the calibrated sensor system. The results show that the proposed sensor has high sensitivity and accuracy in measuring the complex permittivity of liquid samples with volumes as small as 0.13 μL. It provides a useful reference for the complex permittivity characterization of small amount of liquid chemical samples. In addition, the characterization of an important biological sample (inositol) is carried out by using the proposed sensor.

A new photometric method for oxygen consumption measurements in cell suspensions

1986 ◽  
Vol 61 (2) ◽  
pp. 449-455 ◽  
Author(s):  
W. Mueller-Klieser ◽  
R. Zander ◽  
P. Vaupel
Keyword(s):  
Volume Fraction ◽  
High Sensitivity ◽  
Cell Suspensions ◽  
Measuring System ◽  
Photometric Method ◽  
O2 Consumption ◽  
Physical Density ◽  
O2 Concentration ◽  
Consumption Rates ◽  
Time Required

A new technique is described for measuring O2 consumption rates and O2 concentrations in suspensions of respiring cells. Aliquots of a cell suspension kept in a special thermostated precision syringe are injected into the measuring system in defined time intervals. The O2 content of these samples is determined photometrically, as reported previously. The O2 consumption per cellular wet weight and/or per single cell can be calculated from the cell volume fraction, the physical density, the cell concentration in the suspension, and the time-dependent decline of the O2 concentration in the precision syringe. The minimum detectable amount of O2 is 0.1 microliter O2, which corresponds to 0.001 (vol/vol) of O2 if a 100-microliters sample of suspended cells is analyzed. Reproducibility of the O2 consumption measurement is 9% of the measured value. The advantages offered by this method are the straightforward calibration in absolute terms, the short time required for one analysis (2–6 min), a high sensitivity, the simultaneous determination of overall O2 concentration and O2 consumption rates in cell suspensions, and the great variability in the application.

scholarly journals Electric Cell-Substrate Impedance Sensing To Monitor Viral Growth and Study Cellular Responses to Infection with Alphaherpesviruses in Real Time

mSphere ◽  
2017 ◽  
Vol 2 (2) ◽  
Author(s):  
Matthew R. Pennington ◽  
Gerlinde R. Van de Walle
Keyword(s):  
Real Time ◽  
Cellular Response ◽  
Cellular Responses ◽  
Cellular Damage ◽  
Impedance Sensing ◽  
Novel Technologies ◽  
Antiviral Therapies ◽  
Mucosal Surfaces ◽  
Cell Substrate ◽  
Hsv 1

ABSTRACT Alphaherpesviruses, including those that commonly infect humans, such as HSV-1 and HSV-2, typically infect and cause cellular damage to epithelial cells at mucosal surfaces, leading to disease. The development of novel technologies to study the cellular responses to infection may allow a more complete understanding of virus replication and the creation of novel antiviral therapies. This study demonstrates the use of ECIS to study various aspects of herpesvirus biology, with a specific focus on changes in cellular morphology as a result of infection. We conclude that ECIS represents a valuable new tool with which to study alphaherpesvirus infections in real time and in an objective and reproducible manner. Electric cell-substrate impedance sensing (ECIS) measures changes in an electrical circuit formed in a culture dish. As cells grow over a gold electrode, they block the flow of electricity and this is read as an increase in electrical impedance in the circuit. ECIS has previously been used in a variety of applications to study cell growth, migration, and behavior in response to stimuli in real time and without the need for cellular labels. Here, we demonstrate that ECIS is also a valuable tool with which to study infection by alphaherpesviruses. To this end, we used ECIS to study the kinetics of cells infected with felid herpesvirus type 1 (FHV-1), a close relative of the human alphaherpesviruses herpes simplex virus 1 (HSV-1) and HSV-2, and compared the results to those obtained with conventional infectivity assays. First, we demonstrated that ECIS can easily distinguish between wells of cells infected with different amounts of FHV-1 and provides information about the cellular response to infection. Second, we found ECIS useful in identifying differences between the replication kinetics of recombinant DsRed Express2-labeled FHV-1, created via CRISPR/Cas9 genome engineering, and wild-type FHV-1. Finally, we demonstrated that ECIS can accurately determine the half-maximal effective concentration of antivirals. Collectively, our data show that ECIS, in conjunction with current methodologies, is a powerful tool that can be used to monitor viral growth and study the cellular response to alphaherpesvirus infection. IMPORTANCE Alphaherpesviruses, including those that commonly infect humans, such as HSV-1 and HSV-2, typically infect and cause cellular damage to epithelial cells at mucosal surfaces, leading to disease. The development of novel technologies to study the cellular responses to infection may allow a more complete understanding of virus replication and the creation of novel antiviral therapies. This study demonstrates the use of ECIS to study various aspects of herpesvirus biology, with a specific focus on changes in cellular morphology as a result of infection. We conclude that ECIS represents a valuable new tool with which to study alphaherpesvirus infections in real time and in an objective and reproducible manner.

Electrical cell-substrate impedance sensing as a non-invasive tool for cancer cell study

The Analyst ◽  
2011 ◽  
Vol 136 (2) ◽  
pp. 237-245 ◽  
Author(s):  
Jongin Hong ◽  
Karthikeyan Kandasamy ◽  
Mohana Marimuthu ◽  
Cheol Soo Choi ◽  
Sanghyo Kim
Keyword(s):  
Cancer Cell ◽  
Impedance Sensing ◽  
Non Invasive ◽  
Cell Substrate ◽  
Cell Study

scholarly journals Comparison of Leading Biosensor Technologies to Detect Changes in Human Endothelial Barrier Properties in Response to Pro-Inflammatory TNFα and IL1β in Real-Time

Biosensors ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 159
Author(s):  
James J. W. Hucklesby ◽  
Akshata Anchan ◽  
Simon J. O'Carroll ◽  
Charles P. Unsworth ◽  
E. Scott Graham ◽  
...  
Keyword(s):  
Human Brain ◽  
Real Time ◽  
Barrier Properties ◽  
Endothelial Barrier ◽  
Endothelial Monolayer ◽  
Impedance Sensing ◽  
Endothelial Monolayers ◽  
Impedance Data ◽  
Cell Substrate ◽  
Limited Frequency

Electric Cell-Substrate Impedance Sensing (ECIS), xCELLigence and cellZscope are commercially available instruments that measure the impedance of cellular monolayers. Despite widespread use of these systems individually, direct comparisons between these platforms have not been published. To compare these instruments, the responses of human brain endothelial monolayers to TNFα and IL1β were measured on all three platforms simultaneously. All instruments detected transient changes in impedance in response to the cytokines, although the response magnitude varied, with ECIS being the most sensitive. ECIS and cellZscope were also able to attribute responses to particular endothelial barrier components by modelling the multifrequency impedance data acquired by these instruments; in contrast the limited frequency xCELLigence data cannot be modelled. Consistent with its superior impedance sensing, ECIS exhibited a greater capacity than cellZscope to distinguish between subtle changes in modelled endothelial monolayer properties. The reduced resolving ability of the cellZscope platform may be due to its electrode configuration, which is necessary to allow access to the basolateral compartment, an important advantage of this instrument. Collectively, this work demonstrates that instruments must be carefully selected to ensure they are appropriate for the experimental questions being asked when assessing endothelial barrier properties.

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