Available for Licensing
US Patent: US 2020/0324289
Thomas Chen
Daniel Ball
Caleb Begly
Jessy McGowan
Jessy.McGowan@colostate.edu
970-491-7100
At a Glance
Investigators at Colorado State University have developed a Smart Well Device and Multimodal System. The system incorporates a smart well plate having miniature sensors inside each well to allow real-time monitoring of biological processes within each well. Furthermore, the set of sensors can be configured to allow customization and data can be augmented using optical imaging. The smart well plate may be operated as a stand-alone device, or incorporated into the larger Multimodal system, having an environmentally regulated chamber and motor system equipped with built-in optical microscopy with sophisticated software for real-time monitoring, observation, and multi-analyte analysis of biological samples all-in-one.
The environmentally regulated bioanalysis chamber with imaging allows scientists to run experiments within an environment with known temperature, humidity, and oxygen levels. Unlike existing chambers that only regulate temperature and humidity, The Multimodal system here is capable of regulating oxygen concentration for hypoxic conditions to mimic various cellular environments, such as the digestive tract.
Background
The determination of various cellular metabolic parameters, such as oxygen consumption rate (OCR) and extracellular acidification (ECAR), is helpful in the understanding of bioenergetics in health and disease. Abnormal cellular bioenergetics has been associated with diseases such as obesity, diabetes, cancer, neurodegeneration, and cardiomyopathy, for example. Mitochondrial respiration and glycolytic metabolism can be estimated by measuring changes in dissolved oxygen and pH.
However, OCR does not provide direct information about cellular substrate utilization, and ECAR can result from both glycolysis and oxidative metabolism. OCR and ECAR data alone may provide misleading results. Thus, co-measurement of other critical analytes such as extracellular glucose and lactate flux along with OCR and ECAR may provide further insight into cellular metabolic processes.
Optical techniques, including florescence imaging, can typically be used for separately measuring analytes of interest discussed above.
Optical measurement systems for imaging multiple samples typically include a plurality of wells seeded with a volume of cells and a single microscope which moves between each sample at predetermined intervals for imaging. Thus, such systems are not designed for real-time, single-cell, or simultaneous multiple analyte measurements. Even though, it is possible to devise multiple optical sensors for multiple wells for simultaneously measuring florescent/photobleaching intensity, such systems are typically very expensive. Existing electrochemical techniques also do not incorporate multi-analyte measurement seamlessly in a highly integrated and compact system. Accordingly, a need exists for real-time, single- and/or multi-cell, and simultaneous multiple analyte measurements in a highly integrated system that can be easily incorporated into the existing medical/biological technology ecosystem.
Overview
The smart well plates have the same size and the same well format as the traditional well plates – having a 6 to 24 well plate format. The smart well plate device consists of two parts: the disposable wells with custom-designed sensors at the bottom of the well; and the plate body with supporting electronics and wireless communication channels. Each well has a glass bottom with gold-plated electrodes. The well wall is a bio-compatible PMMA or CNC material mounted to the glass bottom. Each well in the smart well plate can be individually swapped in and out depending on the type of sensors are needed for a given well. The well is made for one-time use and disposable. The wells currently supports sensors for oxygen, glucose, lactate, and pH. Extensions to include glutamine, citrate, and nitrate are currently under development. The electrodes from the sensors are pinned out and connected to the electronic components on the plate body via a pinch-able pins to allow easy swap-in and swap-out of the wells from the device.
Incorporation of the smart well plate within the multimodal system allows for an all-in-one research platform. From the system interface, operation of the environmental chamber and internal optical microscope allows for real time, multi-analyte data capture. Data is subsequently transmitted via Bluetooth or WiFi for analysis.
Benefits
- Cost effective
- User friendly
- Multi functions
- Optimized size
- Provides continuous monitoring
- Provides simultaneous monitoring of target analytes
- Wireless interface
Applications
- Environmental measurements
- Live tissue and associated biomarker research
- Real-time cell culture, growth and cell counting experiments
- Standard and sophisticated monitoring
- Academic Biomedical and Chemistry research Labs
- Medical device
- Biomedical science education
Last updated: June 2023
