Bhargab B. Bhattacharya

Waste-aware dilution and mixing of biochemical samples with digital microfluidic biochips

A key challenge in design automation of digital microfluidic biochips is to carry out on-chip dilution/mixing of biochemical samples/reagents for achieving a desired concentration factor (CF). In a bioassay, reducing the waste is crucial because the waste droplet handling is cumbersome and the number of waste reservoirs on-chip needs to be minimized to use limited volume of sample and expensive reagents and hence to reduce the cost of a biochip. The existing dilution algorithms attempt to reduce the number of mix/split steps required in the process but focus little on minimization of sample requirement or waste droplets. In this work, we characterize the underlying combinatorial properties of waste generation and identify the inherent limitations of two earlier mixing algorithms (BS algorithm by Thies et al., Natural Computing 2008; DMRW algorithm by Roy et al., IEEE TCAD 2010) in addressing this issue. Based on these properties, we design an improved dilution/mixing algorithm (IDMA) that optimizes the usage of intermediate droplets generated during the dilution process, which in turn, reduces the demand of sample/reagent and production of waste. The algorithm terminates in O(n) steps for producing a target CF with a precision of 1/2n. Based on simulation results for all CF values ranging from 1/1024 to 1023/1024 using a sample (100% concentration) and a buffer solution (0% concentration), we present an integrated scheme of choosing the best waste-aware dilution algorithm among BS, DMRW, and IDMA for any given value of CF. Finally, an architectural layout of a DMF biochip that supports the proposed scheme is designed.

Layout-Aware Solution Preparation for Biochemical Analysis on a Digital Microfluidic Biochip

A biochemical analysis is based on several laboratory protocols that require repeated mixing of samples with reagents. Sample preparation and analyte identification steps in such bioassays often involve mixing for solution preparation, i.e., various fluids are to be mixed in a certain volumetric ratio in their resulting mixture. We present an efficient approach for automated mixing of three or more fluids on a droplet based digital micro fluidic biochip and design a layout for implementing this algorithm. The proposed method reduces the droplet transportation time from boundary reservoirs to on chip mixers as well as cross-contamination among overlapping droplet routing paths. Simulation of several example solutions reveals encouraging results.

On residue removal in digital microfluidic biochips

Multiplexing several assays in time on the same digital microfluidic biochip is often needed in several biochemical applications. Contamination may lead to undesirable mixing of the residue left by one assay with the droplets of the subsequent assay. Hence, cleaning the droplet pathways of such a biochip by wash droplets between successive assays is required. Since a wash droplet may have a finite capability of residue removal, one has to design an efficient route planning for wash droplet(s) that minimizes the washing time and/or electrode actuation. In this paper, we formulate the problem in terms of graph Eulerization and Capacitated Chinese Postman Problem. We also propose efficient solutions and report some simulation results.

Fault diagnosis in reversible circuits under missing-gate fault model

This article presents a novel technique for fault detection as well as fault location in a reversible combinational circuit under the missing gate fault model. It is shown that in an (nxn) reversible circuit implemented with k-CNOT gates, addition of only one extra control line along with duplication each k-CNOT gate, yields an easily testable design, which admits a universal test set (UTS) of size (n+1) that detects all single missing-gate faults (SMGFs), repeated-gate faults (RGFs), and partial missing-gate faults (PMGFs) in the circuit. Furthermore, storage of only one vector (seed) of the UTS is required; the rest can be generated by n successive cyclic bit-shifts from the seed. For fault location under the SMGF model, a technique for identifying the faulty gate is also presented that needs application of a single test vector, provided the circuit is augmented with some additional observable outputs.

Test Planning in Digital Microfluidic Biochips Using Efficient Eulerization Techniques

Digital microfluidic technology is now being extensively used for implementing a lab-on-a-chip. Microfluidic biochips are often used for safety-critical applications, clinical diagnosis, and for genome analysis. Thus, devising effective and faster testing methodologies to warrant correct operations of these devices after manufacture and during bioassay operations, is very much needed. In this paper, we propose an Euler tour based technique to obtain the route plan of a test droplet for the purpose of structural testing of biochips. The method is applicable to various digital microfluidic biochip architectures, e.g., fully reconfigurable arrays, application specific biochips, pin-constrained irregular geometry biochips, and to defect-tolerant biochips. We show that in general, the optimal Eulerization and subsequent determination of an Euler tour in the graph model of a biochip can be abstracted in terms of the classical Chinese postman problem. The Euler tour can be identified by running the classical Hierholzer’s algorithm, which relies on a simple cycle decomposition and splicing method. This improved Eulerization technique leads to an efficient test plan for the chip. This can also be used in phase-based test planning that yields savings in testing time. The method provides a unified approach towards structural testing and can be easily adopted to design a droplet routing procedure for functional testing of digital microfluidic biochips.

Entropy-based automatic segmentation of bones in digital X-ray images

Bone image segmentation is an integral component of orthopedic Xray image analysis that aims at extracting the bone structure from the muscles and tissues. Automatic segmentation of the bone part in a digital X-ray image is a challenging problem because of its low contrast with the surrounding flesh, which itself needs to be discriminated against the background. The presence of noise and spurious edges further complicates the segmentation. In this paper, we propose an efficient entropy-based segmentation technique that integrates several simple steps, which are fully automated. Experiments on several X-ray images reveal encouraging results as evident from a segmentation entropy quantitative assessment (SEQA) metric [Hao, et al. 2009].

Construction of 3D orthogonal cover of a digital object

The orthogonal cover of a 3D digital object is a minimum-volume 3D polytope having surfaces parallel to the coordinate planes, and containing the entire object so as to capture its approximate shape information. An efficient algorithm for construction of such an orthogonal cover imposed on a background grid is presented in this paper. A combinatorial technique is used to classify the grid faces constituting the polytope while traversing along the surface of the object in a breadthfirst manner. The eligible grid faces are stored in a doubly connected edge list, using which the faces are finally merged to derive the isothetic polygons parallel to the coordinate planes, thereby obtaining the orthogonal cover of the object. The complexity of the cover decreases with increasing grid size. The algorithm requires computations in integer domain only and runs in a time linear in the number of voxels constituting the object surface. Experimental results demonstrate the effectiveness of the algorithm.

Diagnosis of Multiple Scan-Chain Faults in the Presence of System Logic Defects

We present a combined hardware-software based approach to scan-chain diagnosis, when the outcome of a test may be affected by system faults occurring in the logic out-side of the scan chain. For the hardware component we adopt the double-tree scan (DTS) chain architecture, which has previously been shown to be effective in reducing power, volume, and application time of tests for stuck-at and delay faults. We develop a version of flush test which can resolve a multiple fault in a DTS chain to a small number of suspect candidates. Further resolution to a unique multiple fault is enabled by the software component comprising of fault simulation and analysis of the response of the circuit to test patterns produced by ATPG. Experimental results on benchmark circuits show that near-perfect scan-chain diagnosis for multiple faults is possible even when a large number of random system faults are injected in the circuit.

On the representation of a digital contour with an unordered point set for visual perception

In this paper, we study the problem of representing the boundary of a digital object with an unordered set of points (pixels) chosen from its 1-pixel wide contour such that its shape is visually perceptible and uniquely reconstructible. Extraction of such a set is important from the viewpoint of shape description and may also offer potential solutions to various applications like object representation, recognition, and discrimination. We propose a novel technique of determining an irredundant point set from a digital contour using the classical concept of pointillism. Pointillism, a movement of painting with dots that would blend in the viewers eye, was developed by certain Neo-Impressionists of France late in the 19th century. In order to extract the representative point set, we first consider the digitally straight pieces constituting the contour and then obtain a digital polygon P that approximates the bounding curve in a compact form. The polygon P, defined in terms of its ordered set of vertices, is replaced, in turn, with an irredundant set P^ of pseudo-vertices lying on its digital edges, so that the union of P and P^ produces an unordered point set that obviates the vertex ordering but captures the underlying geometric orderliness and the neighborhood relations defining the boundary of the original object. The pseudo-vertices may be chosen by controlling a parameter called pointillist factor that governs our visual perception with the nearest-neighbor correlation of a point set. The pointillist factor can be regulated to control the prominence of the underlying object with its unordered set of points - a strong outcome that establishes the technique about its ability to capture the shape information by an order-free point set of optimal or suboptimal size. We have also given a reconstruction procedure along with an error analysis related with the concerned descriptor. Experimental results on several databases demonstrate its elegance and effectiveness.

Efficient Word Segmentation and Baseline Localization in Handwritten Documents Using Isothetic Covers

Analysis of handwritten documents is a challenging task in the modern era of document digitization. It requires efficient preprocessing which includes word segmentation and baseline detection. This paper proposes a novel approach toward word segmentation and baseline detection in a handwritten document. It is based on certain structural properties of isothetic covers tightly enclosing the words in a handwritten document. For an appropriate grid size, the isothetic covers successfully segregate the words so that each cover corresponds to a particular word. The grid size is selected by an adaptive technique that classifies the inter-cover distances into two classes in an unsupervised manner. Finally, by using a geometric heuristic with the horizontal chords of these covers, the corresponding baselines are extracted. Owing to its traversal strategy along the word boundaries in a combinatorial manner and usage of limited operations strictly in the integer domain, the method is found to be quite fast, efficient, and robust, as demonstrated by experimental results with datasets of both Bengali and English handwritings.