ACAPELLA-1K: a biomechatronic fluid handling system for genome analysis that processes 1000 samples in 8 hours

Abstract-Solution-preparation is a basic and repetitive step for many biological and chemical experiments in the laboratory. It uses stock solutions of sample, reagents, and diluents to derive various mixed solutions with the required concentration levels. Manual solution-preparation methods are time-consuming, imprecise, and they require large volumes of liquid. We propose an electrowetting-based "digital" microfluidic biochip design for automated solution-preparation. An efficient solutionpreparation algorithm is also presented to generate a preparation plan that lists the intermediate mixing steps needed to generate the target solutions with the required concentrations. It determines the type, concentration, and the number of dispensed droplets of stock solutions. The proposed automated solutionpreparation algorithm and biochip platform are evaluated using a protein-crystallization application.

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“…Fluid-handling robots have been developed and used for automated solution-preparation [1,2,3]. However, these robots suffer from many drawbacks.…”

Section: Introductionmentioning

confidence: 99%

“…However, these robots suffer from many drawbacks. First, they rely on high-accuracy microtubes and microtips, which are expensive and fragile [1,2]. Moreover, most fluid-handling robots can only process solutions whose volumes are in the range of microliter or higher.…”

Section: Introductionmentioning

confidence: 99%

Automated, accurate, and inexpensive solution-preparation on a digital microfluidic biochip

Pamula

Chakrabarty

2008

2008 IEEE Biomedical Circuits and Systems Conference

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“…3) Arrays may be prefabricated by a range of methods, from simple methods with syringes to robotics. [22][23][24] Prefabricated arrays of plugs sealed in capillaries may be stored for months and could be made sterile or prepared under inert atmosphere, thereby expanding the range of potential applications. 4) The method is very simple for the end user-no sophisticated equipment is required at the user3s end except a source of constant flow to drive the two streams to merge.…”

mentioning

confidence: 99%

A Microfluidic Approach for Screening Submicroliter Volumes against Multiple Reagents by Using Preformed Arrays of Nanoliter Plugs in a Three‐Phase Liquid/Liquid/Gas Flow

Zheng

Ismagilov

2005

Angewandte Chemie

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Plugging a gap in screening-Arrays of nanoliter-sized plugs of different compositions can be preformed in a three-phase liquid/liquid/gas flow. The arrays can be transported into a microfluidic channel to test against a target (see schematic representation), as demonstrated in protein crystallization and an enzymatic assay.Keywords crystal growth; enzymatic arrays; microreactors; screening methods; three-phase system Herein, we describe a simple, economical microfluidic method of screening a small volume (down to submicroliter volumes) of a solution against a large number of reagents on the nanoliter scale. The use of microfluidics to miniaturize chemical and biological screening is an important and active area of research in such diverse areas as biochemical assays, protein crystallization, and combinatorial chemistry. [1][2][3][4][5][6][7] Nanoliter aqueous plugs (droplets) transported through microchannels in an immiscible liquid have been used in a liquid/liquid flow system and allow miniaturization while eliminating dispersion, [8,9] accelerating mixing, [10] and providing control over the surface chemistry. [11] Applications of such systems to protein crystallization, [3,12] kinetic measurements, [10] assays, [13,14] DNA analysis, [8] and chemical synthesis [15] have been demonstrated. Such plug-based microfluidic systems have been especially attractive for applications in which the concentrations of several reagents had to be varied. The concentrations were varied by rapidly changing the flow rates of the reagent streams as the droplets were formed. [3,12] Plugbased methods of that type require equipment for varying flow rates, and even though such equipment could be as simple as a few computer-controlled syringe pumps, this requirement presents a barrier to many potential users in chemical and biochemical laboratories. In addition, to increase the number of reagents that can be screened, both the number of the microfluidic channels in the device and the number of flow control devices have to be increased proportionally. Herein, we implement a complementary approach that uses pre-formed arrays of plugs to simplify the experiment for the user, relies on a liquid/liquid/gas three-phase flow system to ensure robustness, and allows a much larger number of reagents to be tested in a scalable fashion.

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“…The initial concepts and proof-of-concept for this system were presented in [4] and the first generation ACAPELLA-1K processor was presented in [6]. The ACAPELLA-5K processor presented here, capable of processing 5,000 samples in 8 hours, has been built and is undergoing initial testing.…”

Section: Discussionmentioning

confidence: 99%

“…For details of the specific subsystems on ACAPELLA, see [6]. One important difference to note is that the aspirator and mixer in the ACAPELLA-1K system have been combined into one device on the ACAPELLA-5K system.…”

Section: A Acapella-5k Core Processormentioning

confidence: 99%

Automated microfluidics for genomics

Meldrum

Pence

Moody

et al.

2001 Conference Proceedings of the 23rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society

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Abstract--The Genomation Laboratory at the University of Washington is developing an automated fluid handling system called "Acapella" to prepare microliter reactions for genome analysis. The system prepares 5,000 samples in 8 hours for general-purpose chemistry analysis including DNA sequencing reaction preparation. Keywords--Automation, DNA sequencing, microfluidics, biotechnology, biomechatronics, genomics I. INTRODUCTIONMotivated by the Human Genome Project (HGP) and the biotechnology revolution, an exponential growth in genome automation has occurred over the past several years [1]. Solutions include robots that mimic manual procedures in the laboratory, automated systems that improve performance for specific tasks, to microfabricated chips that perform microfluidic analysis of DNA samples. For a review of genome automation, see [2][3]. For an introduction to DNA sequencing and the automation of it, see [4].In the Genomation Laboratory at the Univ. of Washington (http://rcs.ee.washington.edu/GNL/genomation.html) and with Orca Photonic Systems, Inc. (Redmond, WA), an automated submicroliter fluid sample preparation system called ACAPELLA is being developed. Reactions such as restriction enzyme digests, polymerase chain reactions (PCRs), and sequencing reactions are prepared in glass capillaries, one per sample, with an automated system that can process 5,000 samples in 8 hours. On-going development includes new, fully automated modules for thermal processing of capillaries, real-time DNA quantitation, and purification of DNA inside of capillaries to prepare the samples for DNA sequencing. Applications of the technology include minimal residual disease quantification and sample preparation for DNA. Preliminary work on the ACAPELLA is presented in [4][5]. This paper presents the current development on the ACAPELLA core processor and the thermal cycling module. II. SIGNIFICANCEThe goals of the ACAPELLA system are 1) to develop a very high-throughput (5000 samples in 8 hours) fluid handling system with minimal recurring labor costs, 2) to reduce by tenfold the typical DNA sample volumes for Polymerase Chain Reaction (PCR) and sequencing reactions over current practice, with a proportionate reduction in reagent costs, and 3) to develop a closed sample-processing pipeline. The core technology comprises a system capable of mixing an incoming DNA sample with appropriate reagents in a capillary under full automation.In [5] the significance of the throughput, cost reduction, process benefits, and cost/benefit analysis of the ACAPELLA system is described. In short, the system prepares small 0.5 -2 µl reaction volumes, maintains a 100 to 300 picoliter reagent dispense resolution, retains high mixing precision and quality in small volumes, and demonstrates the ability to achieve high quality, reproducible biology without contamination. The high throughput capability is competitive with large scale robotic batch processing. III. INSTRUMENTATION AND METHODSThe core ACAPELLA sample processor embodies two essential concepts:...

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ACAPELLA-1K: a biomechatronic fluid handling system for genome analysis that processes 1000 samples in 8 hours

Cited by 11 publications

References 21 publications

Automated, accurate, and inexpensive solution-preparation on a digital microfluidic biochip

Automated, accurate, and inexpensive solution-preparation on a digital microfluidic biochip

A Microfluidic Approach for Screening Submicroliter Volumes against Multiple Reagents by Using Preformed Arrays of Nanoliter Plugs in a Three‐Phase Liquid/Liquid/Gas Flow

Automated microfluidics for genomics

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