Isothermal calorimetry measures the heat flow of biological processes, which is proportional to the rate at which a given chemical or physical process takes place. Modern isothermal microcalorimeters make measurements of less than a microwatt of heat flow possible. As a result, as few as 10 000-100 000 active bacterial cells in culture are sufficient to produce a real-time signal dynamically related to the number of cells present and their activity. Specimens containing bacteria need little preparation, and isothermal microcalorimetry (IMC) is a nondestructive method. After IMC measurements, the undisturbed samples can be evaluated by any other means desired. In this review, we present a basic description of microcalorimetry and examples of microbiological applications of IMC for medical and environmental microbiology. In both fields, IMC has been used to quantify microbial activity over periods of hours or even days. Finally, the recent development of highly parallel instruments (up to 48 channels) and the constantly decreasing costs of equipment have made IMC increasingly attractive for microbiology. Miniaturization of isothermal calorimeters provides an even wider range of possibilities.

Use of isothermal microcalorimetry to monitor microbial activities

A module may be provided with at least one opening, the opening being an endpoint of a microfluidic channel that passes through at least part of the module. A set of multiple such modules may be arranged into an arrangement of modules, which may be coupled together using one or more coupling mechanisms included on each module. The arrangement of modules may fit within a regular polyhedral grid, and each module within the arrangement of modules may have a form suitable for arrangement of the modules within the regular polyhedral grid. Fluid may then flow through at least a subset of the arrangement of modules via the microfluidic channel of each module of the subset of the arrangement of modules. Some modules may include sensors, actuators, or inner microfluidic channel surface coatings. The arrangement of modules may form a microfluidic circuit that can perform a microfluidic circuit function.

https://www.pnas.org/content/pnas/111/42/15013.full.pdf

Discrete elements for 3d microfluidics

High-sensitivity microfluidic calorimeters raise the prospect of achieving high-throughput biochemical measurements with minimal sample consumption. However, it has been challenging to realize microchip-based calorimeters possessing both high sensitivity and precise sample-manipulation capabilities. Here, we report chip-based microfluidic calorimeters capable of characterizing the heat of reaction of 3.5-nL samples with 4.2-nW resolution. Our approach, based on a combination of hard- and soft-polymer microfluidics, provides both exceptional thermal response and the physical strength necessary to construct high-sensitivity calorimeters that can be scaled to automated, highly multiplexed array architectures. Polydimethylsiloxane microfluidic valves and pumps are interfaced to parylene channels and reaction chambers to automate the injection of analyte at 1 nL and below. We attained excellent thermal resolution via on-chip vacuum encapsulation, which provides unprecedented thermal isolation of the minute microfluidic reaction chambers. We demonstrate performance of these calorimeters by resolving measurements of the heat of reaction of urea hydrolysis and the enthalpy of mixing of water with methanol. The device structure can be adapted easily to enable a wide variety of other standard calorimeter operations; one example, a flow calorimeter, is described.

https://www.pnas.org/content/pnas/106/36/15225.full.pdf

High-sensitivity microfluidic calorimeters for biological and chemical applications

Microbial growth and isothermal microcalorimetry: Growth models and their application to microcalorimetric data

Introduction: A key part of drug design and development is the optimization of molecular interactions between an engineered drug candidate and its binding target. Thermodynamic characterization provides information about the balance of energetic forces driving binding interactions and is essential for understanding and optimizing molecular interactions. Areas covered: This review discusses the information that can be obtained from thermodynamic measurements and how this can be applied to the drug development process. Current approaches for the measurement and optimization of thermodynamic parameters are presented, specifically higher throughput and calorimetric methods. Relevant literature for this review was identified in part by bibliographic searches for the period 2004 – 2011 using the Science Citation Index and PUBMED and the keywords listed below. Expert opinion: The most effective drug design and development platform comes from an integrated process utilizing all available information from structur...

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Thermodynamic studies for drug design and screening.

A new micro-fluid chip calorimeter for biochemical applications

A micro-fluid chip calorimeter measuring system with highly stable thermostat (0.1 mK) was developed based on an improved nano calorimetry thin-film thermopile chip with excellent chemical and mechanical reliability fabricated in SU-8 technology for insulation and passivation layers. Biochemical processes (e.g. enzyme catalyzed reaction) can be investigated with heat power detection limit

M. Nietzsch

Papers

A new micro-fluid chip calorimeter for biochemical applications

Highly sensitive thermopile heat power sensor for micro-fluid calorimetry of biochemical processes

Nano-calorimetry of small-sized biological samples