The study of cell proliferation is of great importance for medical and biological research, as well as for industrial applications. To render the proliferation process accurately over time, real-time cell proliferation assay methods are required. This work presents a novel real-time and label-free approach for monitoring cell proliferation by continuously measuring changes in thermal properties that occur at the sensor interface during the process. The sensor consists of a single planar resistive structure deposited on a thin foil substrate, integrated at the bottom of a cell culture reservoir. During measurement, the structure is excited with square wave current pulses. Meanwhile, the temperature-induced voltage change measured over the structure is used to derive variations in the number of cells at the interface. This principle is demonstrated first by performing cell sedimentation measurements to quantify the presence of cells at the sensor interface in the absence of cell growth. Later, cell proliferation experiments were performed, whereby parameters such as the available nutrient content and the cell starting concentration were modified. Results from these experiments show that the thermal-based sensor is able to accurately measure variations in the number of cells at the interface. Moreover, the influence of the modified parameters could be observed in the obtained proliferation curves. These findings highlight the potential for the presented thermal method to be incorporated in a standardized well plate format for high-throughput monitoring of cell proliferation.
Multidevice synchronous measurement and thus a fusion of data from multiple sensor sources is becoming a fundamental but nontrivial task. Essentially, different sensors have their own limitations and uncertainties; the fusion of the data serves to increase the accuracy of performance. This research aims to expand the possibilities of multiparameter sensing by integrating impedance and thermal sensors into a microplate format for the simultaneous assessment of electrical and thermal properties. The sensor uses a modified transient plane source (TPS) measuring principle to monitor thermal changes and interdigitated electrodes (IDEs) for impedance analysis. The sensor is put to the test in the characterization of different glycerol and NaCl dilutions based on the varying thermal and electrical properties. At last, to demonstrate the added value of data fusion for liquid identification, a proof-of-application experiment shows the identification of fruit juices based on both measurands using a Gaussian mixture model. These experiments already highlight the power of this combined measuring technology in simple liquid identification processes, hence showing great potential to develop advanced diagnostics in various fields, such as healthcare, biology, or food quality by providing the ability to effectively perform parallel impedance and thermal-based measurements.
23 October 2020 in IEEE Transactions on Instrumentation and Measurement
In many sensing applications, ranging from processes monitoring to bioassays, interactions occur between a thin film and a liquid medium. For such applications, it is generally crucial to monitor physical changes in the film over time. Consequently, the demand for sensitive, yet robust readout methods that can be used to do so is high. In this article, we present a new, thermal-based readout principle that can be applied to monitor physical changes in thin samples over time. This new Transient Thermal Offset (TTO) method is derived from the widely used Transient Plane Source (TPS) method, but intentionally deviates from the condition to not apply thermal pulses that probe deeper than the boundaries of the thin sample. By doing so, it is possible to use the properties of the sample on top of the film as a reference with the novel data processing method. The sensing principle was first demonstrated via numerical simulations in COMSOL Multiphysics. software. Then, for experimental validation, we performed TTO measurements to monitor the removal process of a thin film over time. The results show that the TTO method can be used reliably in practice for monitoring physical changes in thin films. Since also the properties of the surrounding material are measured, it is possible to distinguish between changes in the thin film and changes in the direct environment.
Measurements of thermal conductivity on microliter-sized samples can be of great value in applications where the sample fluid is costly or scarcely available. Such measurements can be used for a broad range of purposes such as quality control and bioanalytical applications. Currently available methods for measuring the thermal conductivity of small liquid samples are often not suited for high-throughput testing due to the complexity of the sensor hardware, or the complexity of the required data processing. In this study, a novel sensor device and sensing method are presented that require only one simple planar resistive sensing structure to be incorporated in a microchannel. The working principle of the so-called Transient Thermal Offset (TTO) method is demonstrated with numerical simulations, as well as by practical experiments on various water/ethanol mixtures using an in-house designed prototype sensor device. The developed device is able to determine the thermal conductivity of water/ethanol mixtures with volumes less than 3 μl with an accuracy of 0.5%. The standard deviation on the experimental measurements is less than 0.009 W/mK. The setup enables rapid testing of small amounts of static liquid samples at high-throughput, as well as long-time monitoring of changes in thermal conductivity of liquids inside a microchannel. The purposeful sensor design enables further miniaturization that would allow testing even smaller sample volumes.
Deposition of minerals, particularly calcium phosphates such as hydroxyapatite, is an important process in the formation of hard tissues such as bone. Herein, a new, affordable, straightforward and nondestructive method based on complex capacitance spectroscopy, an application of electrochemical impedance spectroscopy, is described which allows repeated and real‐time measurements of the same sample throughout the calcium phosphate deposition process. In contrast with end‐point assays which require large numbers of samples to obtain useful time‐course data, this method allows the kinetics of deposition to be measured using a single sample by measuring the impedance of a pair of interdigitated electrodes at a range of frequencies as the layer of mineral is deposited. Changes in the complex capacitance curve over time with deposition can be compared with images of the coating deposited on model substrates, and show different behavior depending on the composition of the coating and the conditions of deposition.