CoSyn: Efficient single-cell analysis using a hybrid microfluidic platform

Abstract

Abstract-Single-cell genomics is used to advance our understanding of diseases such as cancer. Microfluidic solutions have recently been developed to classify cell types or perform singlecell biochemical analysis on pre-isolated types of cells. However, new techniques are needed to efficiently classify cells and conduct biochemical experiments on multiple cell types concurrently. System integration and design automation are major challenges in this context. To overcome these challenges, we present a hybrid microfluidic platform that enables complete single-cell analysis on a heterogeneous pool of cells. We combine this architecture with an associated design-automation and optimization framework, referred to as Co-Synthesis (CoSyn). The proposed framework employs real-time resource allocation to coordinate the progression of concurrent cell analysis. Simulation results show that CoSyn efficiently utilizes platform resources and outperforms baseline techniques.

Synthesis of Reconfigurable Flow-Based Biochips for Scalable Single-Cell Screening

“…Unlike the abovementioned methods, this mechanism allows biochip valves to be flexibly addressed, and it is similar to our proposed pin-constrained method. However, [17] considers only reliability issues, e.g., pressure degradation, associated with pinswitching activities, and it does not take into consideration Step 1Step ( [18], [27], (c) a 2-by-2 sorting network [1].…”

“…The simplest form of an RFB that contains more than a single control vector is a 2-by-2 crossbar (also known as a transposer [18]); see Fig. 6.…”

“…These valves also need to be controlled in real-time in response to identified cell types; the control actions for these valves are not known a priori. In [18], an RFB solution was introduced for scalable barcoding using a fully reconfigurable valve-based crossbar, where an n-to-m crossbar can route a barcoding droplet from any of the n inputs to any of the limited m outputs. However, it can be shown that a simple 40-to-4 crossbar requires at least 1344 valves, thus direct-addressing of valves using pressure ports is prohibitively expensive.…”

Fault-tolerant valve-based microfluidic routing fabric for droplet barcoding in single-cell analysis

“…Single-cell analysis is used to gain insights into diseases such as cancer. This analysis is done in three steps, namely cell encapsulation and differentiation [1], droplet barcoding [2], and type-driven cell analysis [3], [4]. Recent developments in microfluidic techniques have paved the way for singlecell analysis on biochips [5].…”

“…Despite the advent of affordable microfluidic technologies, each of these steps in single-cell analysis can only be carried out efficiently in a specific microfluidic technology domain [3], [8]. Therefore, to perform single-cell analysis efficiently on a single chip, a hybrid platform was recently introduced in [2]. This platform consists of components that work in different microfluidic domains.…”