Vanderbilt scientists have created a system in which the effects of various agents on colonies of cells or a single cell can be studied while the cell is maintained in an instrumented microfluidic cavity. The instrument(s) allows for the detection of extracellular, membrane, and intracellular parameters. The incorporation of closed-loop control techniques allows for the continuous monitoring of the health of the cell(s) and adjustment of the environmental and pharmacological parameters that control the cell. The matrix of responses can be used to identify the agent using a database of known responses. Alternatively, the alterations in metabolic activity can be studied using the responses.
The biological cell may act as a parallel processing, non-linear, multistate, analog computer. Because the cell behaves as an analog computer, it can be programmed. Historically, a limited set of interventions has allowed physiologists and engineers to study living cells and characterize the feedback control systems that govern cell function. With the advent of genetic engineering, it is now possible to reprogram the genetic machinery of a cell, although there has been little effort and progress for inserting man-made devices into the control system of a single living cell so as to convert the cell into a programmable computational engine. Hence, there is a need to merge cellular biophysics, microcircuits and microfluidics, and information technology to create, among other things, programmable microsystems that can be used for sensing, feedback, control and analysis of a single cell and/or an array of interconnected and instrumented living cells. Current bio-sensors use biological molecules for specific agent detection via specific binding reactions. However, wide-spectrum detection is expensive, requiring a large quantity of specific cells. In addition, conventional assays lack cellular machinery to increase sensitivity. Therefore, there is also a need to develop new systems and methods that are capable of providing a complete bio-functional signature an agent, environmental contaminant, unknown drug, or other threats for better, fast, sensitive accurate and efficient detection. Technology Description:
This platform technology is amenable for customization in a variety of modes. The common theme is that of (i) maintaining the viability of the cell population through feedback loop control of the microfluidic system and (ii) continuous extracellular and intra-cellular monitoring for a variety of signals. The system is capable of studying the cellular response to a variety of imposed stimuli.
This technology allows for a variety of applications, including:
- Monitoring the status of a cell that is metabolically active
- Detecting the response of a plurality of cells to at least one analyte of interest
- Monitoring the status of at least one cell, wherein the cell has a membrane forming an enclosed structure and defining an intracellular space within
- Measuring the response of at least one cell to a medium, the response being characterized by reaction time
- Discriminating an agent