A reconfigurable continuous-flow fluidic routing fabric using a modular, scalable primitive

IEEE Trans. Comput.-Aided Des. Integr. Circuits Syst.

Schlichtmann

2019

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. Nondeterministic cell-type identification, 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 designautomation 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. Besides this framework, a probabilistic model based on a discrete-time Markov chain (DTMC) is also deployed to investigate protocol settings where experimental conditions, such as sonication time, vary probabilistically among cell types. Simulation results show that CoSyn efficiently utilizes platform resources and outperforms baseline techniques.

Section: (B)mentioning

confidence: 99%

“…4(a), c 1 is equal to T f , whereas c 2 is equal to 2 T f , since even though a diagonal is shown in Fig. 3 as a fluidic path, routing of such paths in a transposer is implemented only along the x-and y-directions and the distances along these dimensions are equal [41]. Fig.…”

Section: Mapping To Algorithmic Models a Modeling Of A Valve-basmentioning

confidence: 99%

Synthesis of a Cyberphysical Hybrid Microfluidic Platform for Single-Cell Analysis

IEEE Trans. Comput.-Aided Des. Integr. Circuits Syst.

Schlichtmann

2019

“…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].…”

Section: A Synthesis Of Flow-based Biochipsmentioning

confidence: 99%

“…3(a) shows an RFB architecture that screens N streams of cells, classifies cells into K types, and barcodes the cells via W ports (W << K). This platform consists of three modules: valve-less fluorescence detection [3], barcoding crossbar [27], and sorting network [1]. Adaptation is achieved via the detection of samples in the fluorescence-detection module, whereas reconfiguration is carried out in response at both the barcoding crossbar and the sorting network.…”

Section: A Synthesis Of Flow-based Biochipsmentioning

confidence: 99%

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

Sridhar

IEEE Trans. Comput.-Aided Des. Integr. Circuits Syst.

et al. 2019

Single-cell screening is used to sort a stream of cells into clusters (or types) based on pre-specified biomarkers, thus supporting type-driven biochemical analysis. Reconfigurable flowbased microfluidic biochips (RFBs) can be utilized to screen hundreds of heterogeneous cells within a few minutes, but they are overburdened with the control of a large number of valves. To address this problem, we present a pin-constrained RFB design methodology for single-cell screening. The proposed design is analyzed using computational fluid dynamics simulations, mapped to an RC-lumped model, and combined with intervalve connectivity information to construct a high-level synthesis framework, referred to as Sortex. Simulation results show that Sortex significantly reduces the number of control pins and fulfills the timing requirements of single-cell screening.

“…In this work, we are focused on droplet barcoding and a valve-based fabric that is utilized as a crossbar to route a barcoding droplet from the reservoirs to the point where it is mixed with sample/reagents droplets [4]. This routing fabric is composed of transposers [9], which are connected using channels and controlled via pneumatic inputs. Fig.…”

Section: Introductionmentioning

confidence: 99%

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

Moradi

2018 Design, Automation &Amp; Test in Europe Conference &Amp; Exhibition (DATE)

et al. 2018

High-throughput single-cell genomics is used to gain insights into diseases such as cancer. Motivated by this important application, microfluidics has emerged as a key technology for developing comprehensive biochemical procedures for studying DNA, RNA, proteins, and many other cellular components. Recently, a hybrid microfluidic platform has been proposed to efficiently automate the analysis of a heterogeneous sequence of cells. In this design, a valve-based routing fabric based on transposers is used to label/barcode the target cells. However, the design proposed in prior work overlooked defects that are likely to occur during chip fabrication and system integration. We address the above limitation by investigating the fault tolerance of the valve-based routing fabric. We develop a theory of failure assessment and introduce a design technique for achieving fault tolerance. Simulation results show that the proposed method leads to a slight increase in the fabric size and decrease in cellanalysis throughput, but this is only a small price to pay for the added assurance of fault tolerance in the new design.