Pin-constrained Digital Microfluidic Biochips Research Articles

On-Line Test of Pin-Constrained Digital Microfluidic Biochips with Connect-5 Structure

Digital microfluidic biochips (DMFBs) are widely used in the field of biochemistry. Effective off-line and on-line test for the biochips are required to ensure the system reliability. For direct addressing digital microfluidic biochips (DDMFBs), each control pin corresponds to only one electrode, and that can facilitate the testing of such biochips. However, in pin-constrained digital microfluidic biochips (PDMFBs), multiple electrodes may share one control pin, and thus the testing will be more difficult. In this paper, the pin constraint formula for PDMFBs with connect-5 structure is derived. A novel pin assignment scheme is also proposed, which can conduct on-line test that rarely considered by the previous methods. Furthermore, a hybrid method combining the priority strategy and genetic algorithm is introduced for the on-line test of pin-constrained digital microfluidic biochip with connect-5 structure. The simulation results show that the shortest test path acquired by the proposed method is equal to the optimal value of Euler path, which indicates that the method can effectively implement the on-line test of PDMFBs with connect-5 structure.

Pin Addressing Method Based on an SVM With a Reliability Constraint in Digital Microfluidic Biochips

Digital microfluidic biochips (DMFBs) are increasingly important and are used for point-of-care, drug discovery, clinical diagnosis, immunoassays, etc. Pin-constrained DMFBs are an important part of digital microfluidic biochips, and they have gained increasing attention from researchers. However, many previous works have focused on the problem of electrode addressing and aimed to minimize the number of control pins in pin-constrained DMFBs. Although the number of control pins can be effectively redistributed through broadcast addressing technology, the chip reliability will be reduced if the signals are shared arbitrarily. Arbitrary signal sharing can lead to a large number of actuations for many idle electrodes, and as a result, a trapping charge or decreasing contact angle problem could occur for some electrodes, reducing the reliability of the chip. To address this problem, the appropriate electrode matching object should be carefully selected, and the influence of these factors on chip reliability should be fully considered. For this purpose, we aimed to fully consider electrode addressing and the reliability of the chip in improving the reliability of DMFBs. This paper proposed a pin addressing method based on a support vector machine (SVM) with the reliability constraint algorithm, which can fully consider the electrode addressing method and the reliability of the chip together. The proposed method achieved an average maximum number of electrode actuations that was 53.8% and 18.2% smaller than those of the baseline algorithm and the graph-based algorithm, respectively. The simulation experiment results showed that the proposed method can efficiently solve reliability problems during the DMFB design process.

Optimization Techniques for the Synchronization of Concurrent Fluidic Operations in Pin-Constrained Digital Microfluidic Biochips

The implementation of bioassays in pin-constrained digital microfluidic biochips may involve pin-actuation conflicts if the concurrently-implemented fluidic operations are not carefully synchronized. We propose a two-phase optimization method to identify and synchronize the fluidic operations that can be executed in parallel. The goal is to implement these fluidic operations without pin-actuation conflict, and minimize the duration of implementing the outcome sequence after synchronization. We also extend the synchronization method with the addition of a small number of control pins, in order to further minimize the completion time while avoiding pin-actuation conflicts. The effectiveness of the proposed synchronization method is demonstrated for a representative 3-plex assay performed on a commercial pin-constrained biochip and for multiplexed in-vitro diagnostics performed on an experimental pin-constrained biochip.

Broadcast Electrode-Addressing and Scheduling Methods for Pin-Constrained Digital Microfluidic Biochips

Recent advances in digital microfluidics have enabled lab-on-a-chip devices for DNA sequencing, immunoassays, clinical chemistry, and protein crystallization. Basic operations such as droplet dispensing, mixing, dilution, localized heating, and incubation can be carried out using a 2-D array of electrodes and nanoliter volumes of liquid. The number of independent input pins used to control the electrodes in such microfluidic “biochips” is an important cost-driver, especially for disposable printed circuit board devices that are being developed for clinical and point-of-care diagnostics. However, most prior work on biochip design-automation has assumed independent control of the electrodes using a large number of input pins. We present a broadcast-addressing-based design technique for pin-constrained multifunctional biochips. The proposed method provides high throughput for bioassays and it reduces the number of control pins by identifying and connecting control pins with “compatible” actuation sequences. We also describe two scheduling methods to map fluidic operations on the pin-constrained design, in order to minimize the completion time while avoiding pin-actuation conflicts. The proposed methods are evaluated using multifunctional chips designed to execute a set of multiplexed bioassays, the polymerase chain reaction, and a protein dilution assay.

A Two-Stage Integer Linear Programming-Based Droplet Routing Algorithm for Pin-Constrained Digital Microfluidic Biochips

With the increasing design complexities, the design of pin-constrained digital microfluidic biochips (PDMFBs) is of practical importance for the emerging marketplace. However, solutions of current pin-count reduction are inevitably limited by simply adopting it after the droplet routing stage. In this paper, we propose the first droplet routing algorithm for PDMFBs that can integrate pin-count reduction with droplet routing stage. Furthermore, our algorithm is capable of minimizing the number of control pins, the number of used cells, and the droplet routing time. We first present a basic integer linear programming (ILP) formulation to optimally solve the droplet routing problem for PDMFBs with simultaneous multiobjective optimization. Due to the complexity of this ILP formulation, we also propose a two-stage technique of global routing followed by incremental ILP-based routing to reduce the solution space. To further reduce the runtime, we present a deterministic ILP formulation that casts the original routing optimization problem into a decision problem, and solve it by a binary solution search method that searches in logarithmic time. Extensive experiments demonstrate that in terms of the number of the control pins, the number of the used cells, and the routing time, we obtain much better achievement than all the state-of-the-art algorithms in any aspect.

Automated design of pin-constrained digital microfluidic biochips under droplet-interference constraints

Microfluidics-based biochips, also referred to as lab-on-a-chip, are devices that integrate fluid-handling functions such as sample preparation, analysis, separation, and detection. This emerging technology combines electronics with biology to open new application areas such as point-of-care diagnosis, on-chip DNA analysis, and automated drug discovery. We propose a design automation method for pin-constrained biochips that manipulate nanoliter volumes of discrete droplets on a microfluidic array. In contrast to the direct-addressing scheme that has been studied thus far in the literature, we assign a small number of independent control pins to a large number of electrodes in the biochip, thereby reducing design complexity and product cost. The design procedure relies on a droplet-trace-based array partitioning scheme and an efficient pin assignment technique, referred to as the “Connect-5 algorithm.” The proposed method is evaluated using a set of multiplexed bioassays.