OCTO

Problem Statement

Spatial Transcriptomics is a relatively new field, with many technologies being severely time or cost-inefficient. Most instruments used have been focused on creating modular or comprehensive packages. This strategy has resulted in microscope prices soaring into the hundreds of thousands as fabricators have to specialize in various technologies. Moreover, as detailed below, the workflow for the process can take weeks as the combination of mapping, barcoding, and sequencing can accumulate with slow equipment. We believe there is a need for a new generation of specialized instruments that will promote the optimization of smaller processes within the workflow. At the bottom of the page, we have laid out how we have accomplished this task under the scope of tissue scanning. 

Spatial Transcriptomics

Spatial transcriptomics is a cutting-edge technology that combines molecular biology and imaging to map gene expression within tissue sections. By using specialized slides with barcoded capture probes, it captures the spatial distribution of RNA molecules, allowing researchers to visualize where specific genes are active within the tissue context. This technique enables a deeper understanding of tissue architecture and cellular functions by preserving spatial information that traditional transcriptomics methods lose. Applications include cancer research, where it helps identify tumor heterogeneity and microenvironment interactions, and neuroscience, where it maps gene activity in complex brain tissues. Overall, spatial transcriptomics provides invaluable insights into the molecular mechanisms underlying health and disease.

Work Flow

1. Sample Preparation (1-2 days)

2. Slide Preparation (1 day)

3. Optional Tissue Staining (1 day)

4. Imaging (1 day)

5. Tissue Permeabilization (a few hours)

6. DNA synthesis and barcoding (1 day)

7. Library Preparation (1-2 days)

8. Sequencing (1-3 days)

9. Data Analysis (1 week)

Solution Overview

After months of careful research and prototyping, the team decided that the scanning function was the target area of improvement. With the time of a single tissue scanning taking up to a day, each trial can take excessive amounts of time to complete. To combat this issue, the team has designed the OCTO, a low-cost microscope capable of scanning a tissue and identifying regions of interest. The finalized design of the microscope does not include microfluidics, but rather: a 3-axis stepper motor stage, whitefield illumination, a 20x objective, a 12-megapixel camera, and a variety of 3D printed components such as the sample holder. The bulk structural components of the microscope were scrapped from spare materials and 3D-printed parts. More on the team's design can be found here.

Inspiration

The team took inspiration for many components of our model from the SQUID [2]. The SQUID is a modular low-cost spatial transcriptomics microscope capable of having pieces switched out for varying processes. While no components were directly taken from the SQUID design, many of the original prototypes which allowed the team to cement their understanding of the project, pulled direct inspiration from the SQUID. The team was originally able to get an understanding of microscope design and production by extensively reading the SQUID's article. Below is a figure demonstrating its design.

References

1. “A Brief Overview of Spatial Transcriptomics.” YouTube, YouTube, 28 Sept. 2017, www.youtube.com/watch?v=rz-Evzk94o0&ab_channel=SpatialTranscriptomics.

2. Li H., et al. “Squid: Simplifying Quantitative Imaging Platform Development and Deployment” bioRxiv (2020).

3. Tian, L., Chen, F. & Macosko, E.Z. The expanding vistas of spatial transcriptomics. Nat Biotechnol41, 773–782 (2023). https://doi.org/10.1038/s41587-022-01448-2

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