Enabling direct microcalorimetric measurement of metabolic activity and exothermic reactions onto microfluidic platforms via heat flux sensor integration

Abstract

All biological processes use or produce heat. Traditional microcalorimeters have been utilized to study the metabolic heat output of living organisms and heat production of exothermic chemical processes. Current advances in microfabrication have made possible the miniaturization of commercial microcalorimeters, resulting in a few studies on the metabolic activity of cells at the microscale in microfluidic chips. Here we present a new, versatile, and robust microcalorimetric differential design based on the integration of heat flux sensors on top of microfluidic channels. We show the design, modeling, calibration, and experimental verification of this system by utilizing Escherichia coli growth and the exothermic base catalyzed hydrolysis of methyl paraben as use cases. The system consists of a Polydimethylsiloxane based flow-through microfluidic chip with two 46 µl chambers and two integrated heat flux sensors. The differential compensation of thermal power measurements allows for the measurement of bacterial growth with a limit of detection of 1707 W/m3, corresponding to 0.021OD (2 ∙ 107 bacteria). We also extracted the thermal power of a single Escherichia coli of between 1.3 and 4.5 pW, comparable to values measured by industrial microcalorimeters. Our system opens the possibility for expanding already existing microfluidic systems, such as drug testing lab-on-chip platforms, with measurements of metabolic changes of cell populations in form of heat output, without modifying the analyte and minimal interference with the microfluidic channel itself.

Finite element-based feasibility study on utilizing heat flux sensors for early detection of vascular graft infections

“…The use of a heat flux sensor allows for the decoupling from globalized temperature fluctuations (fever, sport, and sleep) and focus on the localized heat production by infectious growth. Previous literature show that heat flux sensors embedded in microfluidic chips made of PDMS can detect the onset of bacterial growth from a heat source thermal density of 1707 W/m 3 29 which is in line with the early detection of bacterial growth at the onset of the exponential growth curve. With an approach of having a physical sensor (heat flux sensor) with the potential of long-term stability, we open the possibility of early detection and treatment of implant infections, drastically decreasing the mortality rate from between 17 and 40% 3 .…”

“…An infectious area with a radius of and a thickness of is above the commercial sensor resolution with a heat source of (corresponds to of the thermal power of a biofilm as described in Section 8 in the SI) and can be detected with a heat transfer coefficient of . We have previously shown in an experimental setup with heat flux sensor embedded in PDMS in a microfluidic chip that a heat source of is detectable with a commercial heat flux sensor 29 . In that setup, two heat flux sensors were used to measure the differentially compensated heat signal of bacterial growth through common mode rejection, from the onset throughout the exponential bacterial growth in an in vitro microfluidic chip 29 .…”

The influence of chemical and technological parameters of materials in the design of objects in industrial design on the example of state facilities

“…With a further increase in I 2 , at a certain point, the first maximum merges with the minimum of internal energy, as a result, the system loses stability and quickly passes into a stable state in the region of high density of defects (solid segments of curves 1–4). This transition reflects FP1 and corresponds to an intensive stage of fragmentation, which is accompanied by a sharp decrease in grain sizes and an improvement in the physical and mechanical properties of the metal [32–34]. It is known that in the case of FP1, the system (material) can simultaneously function in two metastable states or phases, which in this case means the simultaneous coexistence of two limit structures with different grain sizes (the realisation of two maxima V (h g )).…”

ZnO/Ag/Reduced Graphene Oxide Nanocomposite as a Conductive Layer for Electrochemical Monitoring of Candida albicans Biofilm Formation and Dynamics

“…Besides, the development of nanomaterials to combat fungal biofilms, another challenge faced in healthcare settings is to detect and monitor the progression/degradation of biofilms on medical devices in a noninvasive manner. Diverse detection techniques, such as turbidity measurement, Fiber optical devices, different flow cells, microfluidic platforms, , and various imaging technologies, have been employed so far to comprehend the properties of biofilms. However, electrochemical sensing systems, have emerged as highly successful tools for real-time monitoring of biofilms because of their ability to study various physical and electrical phenomenon happening at the interface such as changes in the capacitive behavior of the electrical double layer, variation in adsorption or desorption processes, or differences in the charge transfer reaction of an electrode, etc .…”