Developing Nanosensor Chemical Cytometry (NCC) to Support the Development of Cellular Therapeutics

How biology responds to the environment at the cellular level play an important role in human health and diseases. For example, it is common for cells of the same type and origin to be functionally significantly different from one cell to another. While previous methods have studied cell populations as a group, it is becoming increasingly clear that measuring cells individually provides important information that helps to predict their behavior as part of organisms.

Thus, the goal of this project is to develop a new platform for probing the functional properties of cells (i. e., cell cytometry) in a nondestructive way at the single cell level in a rapid manner. This platform will make use of novel nanosensors that can determine the properties of single cells flowing in a microchannel by detecting their reflections when illuminated with near infrared light.

Potential benefits of this platform include earlier detection of chronic conditions such as diabetes and cancer, as many of the initial changes responsible start as functional shifts within a cell population, and enhancement of new research into the use of cells as therapeutics. Because these cells are extracted from patients, it is important to develop techniques to examine their quality at the single-cell level to ensure that they function as intended.

The project will also further educational opportunities for undergraduates, high school students, and underrepresented minorities in the greater Boston area specifically through guided internship programs for teachers and high school and undergraduate underrepresented minority students. The new platform will enhance an ongoing Nanopore Sequencing Laboratory Module by connecting the new cell sensing platform to the existing platform, allowing students to study both the genetic and physical properties of a single cell.

The goal of this project is to utilize the interface of fluorescent nanosensor arrays within high throughput microfluidic channels such that scientifically relevant label free cellular populations can be studied nondestructively at the single cell level. The work builds on studies that will advance a new class of biophotonic monitoring platform pioneered by the investigator’s Lab at MIT.

The sensor consists of near-infrared (nIR) fluorescent single-walled carbon nanotube (SWNT) nanosensors along a microfluidic channel through which flowing cells are guided. These nanosensors can be engineered to be optically responsive to local concentrations of biologically relevant chemical signals. Preliminary results showed that one can utilize the flowing cell itself as a Gaussian lens to amplify the nanosensor emission signal and extract rich information on a per cell basis in real-time.

Due to the investigator’s method of imaging data collection, the biomolecular information extracted can be cross-correlated with individual cellular physical properties. As part of this project, first, the capabilities of such a system to accommodate multiple targeted nanosensors for multiplexed single cell detection will be studied. Next, the physical phenomenon of cellular lensing, including the effects of different cell types and experimental conditions will be studied.

Finally, the newly developed sensor platform will be utilized to study commonly used cell types used in cell therapy, including: monocytes, macrophages, T-cells or neural stem cells.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.