tugas 1 : sistem komputer

Caltech and IBM scientists use self-assembled DNA scaffolding to build tiny circuit boards Nanotechnology advance could lead to smaller, faster, more energy-efficient computer chips


San Jose-CA,17 Agustus 2009

Pasadena,California-Peneliti dari Institut Teknologi California(Caltech) dan pusat peneliti IBM Almaden mengembangkan teknologi baru yg terorientasi dan merupakan potongan self-assembly dari DNA atau yg disebut dengan “DNA origami” di permukaan yang kompatibel dengan peralatan manufaktur semikonduktor.Posisinya tepat berada pada DNA nanostruktur,yg dapat bergilir seperti miniatur papan sirkuit untuk ketepatan assembly dari komponen chip computer.

Kemajuannya,tidak hanya mempermudah manufaktur untuk membuat chip yang lebih kecil, lebih cepat dan powerful, namun juga lebih efisien dan murah. Umumnya processor sekarang dibangun dengan teknologi 32nm, namun IBM menemukan cara untuk mengatasi masalah tersebut dengan membangun chip menggunakan teknologi 22nm, yang sekaligus untuk eksplorasi kelas transistor baru yang menggunakan carbon nanotube atau silicon nanowire.

Struktur DNA origami dapat digambarkan sebagai penerobosan potensial untuk kreasi dari sirkuit nanoscale.Dalam proses pembuatan yg dilakukan oleh peneliti senior Caltech dan bekerja sama dengan Paul W.K Rothemund serta rekannya,molekul DNA self-assembly membangun dirinya sendiri via reaksi ion antara single viral DNA dan campuran synthetic oligonucleotide yang berbeda.Bagian kecil ini memainkan peran sebagai bahan viral DNA yg sangat baik di dalam dua potongan dimensional yg terus melengkapi dasar-pair binding.

Metode itu juga secara efektif memasukkan DNA origami ke dalam nanostruktur seperti dalam bentuk kotak, segitiga dan bintang dengan dimensi 100nm hingga 150nm dan dengan tebal 2 kali panjang helix DNA.

Tapi ada satu masalah untuk menggunakan DNA origami,bagaimanapun itu merupakan struktur pembuatan dalam saltwater solution-mengingat sirkuit elektronik dibuat di dalam permukaan,seperti tablet silicon,sehingga mereka dapat berintegrasi dengan teknologi lain.Selain itu struktur DNA origami juga menempel secara acak pada permukaan,yg artinya “jika kamu mengalirkan DNA origami keluar dari permukaan pada potongan mereka,mereka akan menyerang setiap tempat.Bagian kecil itu seperti permainan kartu,kamu memilih kartunya dan melemparnya ke lantai,mau tak mau mereka berpencar ke seluruh tempat.Seperti mengacak persiapan DNA origami yg sangat tidak berguna.Jika mereka membawa sirkuit elektronik,sebagai contoh,mereka kesulitan untuk menemukan dan memasang kawat ke dalam sirkuit yg lebih besar”jelas Rothemund,orang yg memimpin proyek ini dengan IBM.

Untuk menghilangkan masalah ini,Rothemund dan rekannya di Pusat Penelitian Almaden membangun jalan untuk memposisikan DNA origami nanostruktur pada permukaan yg tepat,”untuk menjajarkan mereka seperti bebek yg berbaris”kata Rothemund.

”Ini menjatuhkan satu masalah utama dalam menggunakan teknologi DNA origami”ia menambahkan.

Dalam proses pembuatan yg dilakukan oleh peneliti IBM yg merupakan ciptaan Rothemund,sinar electron atau optical lithographi dan sketsa plasma oksigen,serta teknik semikonduktor konvensional,digunakan untuk membuat pola susunan di dalam tablet silicon,menimbulkan ukuran lithographi template yg pantas dan mencocokan potongan tersebut dari struktur segitiga individu DNA.Secara negative sketsa potongan-potongan kecil terisi,sebagai struktur DNA origami,dan oleh karena itu “lengket”.

Untuk menyambungkan origami pada template,ion magnesium ditambahkan ke larutan yg mengandung air garam.Secara positif ion magnesium dapat terisi potongan untuk ke dua DNA origami dan secara negative potongan-potongan kecil terisi di dalam template.Jadi,ketika larutan mengalir keluar template,tersusunlah “sandwich” negative-positive-negative,dengan atom magnesium yg berlaku sebagai lem untuk melekatkan origami ke potongan-potongan kecil yg lengket.

“Segitiga mengikat kuat ke potongan-potongan kecil yg lengket,tetapi mereka juga dapat sedikit bergoyang-goyang,sehingga mereka dapat berbaris sejajar dengan potongan-potongan kecil yg lengket.Jadi,kita tidak hanya dapat menempatkan origami dimana pun kita menginginkannya,tetapi mereka juga dapat berorientasi di arah mana pun yg mereka inginkan”kata Rothemund

Posisi DNA nanostruktur dapat berjalan sebagai penopang,atau miniatur papan sirkuit,komponen assembly –seperti carbon nanotubes,nanowires,dan nanoparticles-pada dimensi yg mungkin lebih pintar dari pembuatan teknik konvensional semikonduktor.Kemungkinan ini menimbulkan alat fungsional yg dapat digabungkan ke dalam struktur yg lebih besar,sebaik kemungkinan belajar dari menyatukan nanostruktur dengan mengetahui koordinatnya.

“Jarak diantara komponen dapat mencapai 6 nanometer,sehingga resolusi dari prosesnya kira-kira 10 kali lebih tinggi daripada proses yg sekarang ini kita gunakan untuk membuat chip komputer.Proses ini tidak terbatas hanya untuk mengatur hal yg berkaitan dengan ilmu eksakta dan komputer,seperti komponen elektronik.Sebagai contoh,ahli biologi belajar tentang bagaimana protein berinteraksi pada pola di dalam inti DNA origami.Ini mungkin berguna dalam menyelidiki motor protein,kekuatan mesin kecil yg ada pada otot kita.Mereka bekerja secara bergerombol,mereka menggerakan motor bersama-sama.Untuk mempelajari bagaimana perbedaan susunan dari kerjasama motor,peneliti menggunakan DNA origami untuk mengatur gerombolan tersebut”jelas Rothemund

Referensi : google,IBM articles,& http://media.caltech.edu/press_releases/13284

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Next Generation Sequencing Technology Spotlight

Monday June 01, 2009

by Caitlin Smith

When does a generation of sequencing come to a close, marking the start of a newer one? Though the slower, trusty Sanger sequencing method is still prized for its reliability and long reads lengths, next generation sequencing (NGS) is increasingly accessible, and valued for fast reliable results. “The most exciting developments are in the science enabled by [NGS] technologies,” says Adam Lowe, director of product marketing at Illumina. “[For example,] the ability to sequence multiple human genomes; the myriad new species whose genomes we can decipher; our ability to study the entire transcriptome down to individual splicing events and categorize and quantify the extent of methylation at a base-by-base level throughout the entire genome.” Such feats could not have been accomplished just a few years ago, but are now taking off thanks to NGS.

Faster, better quality data

Anna Berdine, senior market development manager of sequencing systems for Applied Biosystemsat Life Technologies, says that the ability to do in-depth analysis of single genomes with NGS will likely make personalized medicine a reality soon. NGS can do this because it “enables scientists to assay the genome and transcriptome in a truly hypothesis-neutral approach, providing new insights into biology and disease pathogenesis,” says Berdine. Rising to this challenge, NGS technology is delivering higher quality data and longer read lengths. “The SOLiD™ 3 System generates greater than 30 GB of sequence with 600 million mappable reads per run, enabling researchers to discover more with the coverage, accuracy, and sensitivity necessary to detect novel targets down to a single copy per cell,” Berdine says.

SeqWright offers several features that augment the power of NGS—for example, “Sequence Capture Technology using NimbleGen Capture Arrays, multiplexing (bar-coding) and paired-end libraries with 454 Titanium, and SOLiD 3,” says Marc Dantone, marketing manager at SeqWright. “Through our partnership with Roche NimbleGen, we are able to capture the entire human exome from genomic DNA in a matter of days. Following capture, there is sufficient DNA for multiple NGS runs. This opens up many research opportunities for polygenic disease studies or metabolic pathway studies. Furthermore, we can create custom arrays, which capture up to 30 MB of any region, contiguous or otherwise, of the hg18 genome.”

Illumina’s recent release, the Genome AnalyzerIIx, also offers increased throughput, higher-quality data, and longer read lengths. “The GAIIx offers a unique combination of tunable read length and high-throughput, enabling customers to perform the most challenging sequencing applications (such as de novo sequencing and metagenomics) that were previously addressable with long read, lower-throughput technologies,” says Lowe. “The GAIIx also offers real-time basecalling, so the computational infrastructure required for data handling has been greatly reduced at the same time as the system output has been increased.”

As throughput and quality increase, so too do the opportunities to apply NGS to disease research and other types of studies. The Genome Sequencer FLX system from 454 Life Sciences/Roche was recently used to re-sequence genes implicated in type I diabetes. “While genome-wide associated studies (GWAS) are widely used to map genomic regions contributing to common human diseases, they often do not identify the precise causative genes and sequence variants which are essential for clinical applications,” says Katie Montgomery, marketing communications specialist at 454 Life Sciences. “The study marks one of the first of its kind in discovering protective type I diabetes alleles directly from the results of a previously conducted GWAS. The findings and pioneering scientific method will ultimately provide the knowledge to develop better strategies to detect, treat, and prevent genetic-based diseases in the future.” Another new tool for GWAS is sequencing genomic regions captured by Roche NimbleGen Sequence Capture Arrays, which allow the custom capture of up to five MB of genomic DNA in either a contiguous or discontiguous region of interest.

The 454 Sequencing system also gained a new tool in its GS FLX Titanium Library Paired End Adaptors for generating paired end libraries with 3 kb, 8 kb, or 20 kb spans. “Paired end reads (also known as ‘mate pairs’) supplement shotgun reads to improve de novo assemblies by completely or partially spanning highly repetitive genomic regions,” says Montgomery. “With this new, paired end solution, the system can rapidly generate high quality assemblies, even in a single sequencing run. A researcher can routinely generate near-finished quality assemblies of multiple microbial genomes from the data produced in one 10 hour sequencing run.”

The “newest NGS” technologies include the single-molecule sequencing method of Helicos BioSciences. Their Helicos™ Genetic Analysis System, which uses their True Single Molecule Sequencing (tSMS)™ Technology, eliminates the DNA amplification or ligation steps of other NGS methods. “This eliminates amplification and ligation biases from the sequencing data,” says Avak Kahvejian, senior product manager at Helicos. “Also, tSMS allows the parallel analysis of billions of molecules of DNA with a very simple sample preparation process, providing tremendous throughput and cost benefits.”

Important tools

Calibration is inarguably one of the most important steps in any experiment where it’s relevant – so too for NGS. Fluidigm’s SlingShot is a digital PCR kit for next generation sequencers that calibrates sample libraries by quantifying the concentration of DNA libraries before amplification. “Fluidigm has already released assay kits for quantifying 454 shotgun and multiplex libraries, as well as Illumina and SOLiD libraries,” says Martin Pieprzyk, product marketing manager at Fluidigm. SlingShot requires only picograms of DNA, making it suitable for working with rare or clinical samples.

Another new tool from Fluidigm to be released soon is their Access Array, a microfluidic chip designed for high-throughput re-sequencing, as well as “targeted enrichment, sample barcoding for multiplexed sequencing, and library preparation for sequencing using amplicon tagging,” says Pieprzyk. The Access Array can handle 48 samples against 48 amplicons for 2,304 reactions simultaneously. “We believe advances in deep re-sequencing seem to be generating a lot of excitement,” says Pieprzyk. “This targeted re-sequencing (using target enrichment) has become important as researchers look at specific regions of the human genome in large cohort studies. Up to now, large sample studies have been too expensive and labor intensive to be performed on next generation sequencers effectively and efficiently. [Our new Access Array System] allows researchers to target specific areas of interest to be enriched and barcoded so that a large number of samples can be sequenced at the same time.”

Another tool for target enrichment is Agilent’s SureSelect Target Enrichment System. Fred Ernani, senior product manager for emerging genomics applications at Agilent, says the system can be automated and easily scaled for 10 to thousands of samples. “With sample input requirements at or below 3 µg of gDNA, researchers can perform highly targeted next-generation sequencing on the most precious of samples,” says Ernani. “I think that some of the biggest challenges are in the sample preparation workflow. All of the sequencers on the market have fairly complex sample preparation workflows. Some scientists are working to improve the sample preparation process to make it less cumbersome and more reliable.”

Exciting bioinformatics challenge

Next generation sequencing generates mind-boggling amounts of data, creating a big challenge for biologists and computer scientists alike. “The most exciting developments are in bioinformatics, which is beginning to catch up with the output of these next generation platforms,” says Dantone. “What good is all of this sequence data if you can't convert it into information? We have developed several tools in-house in order to help us provide our next-gen clients with just this sort of ‘information’ rather than simply data.” Lowe agrees that bioinformatics growth is a necessity. “We increased the throughput of our system approximately 15-fold in 12 months,” he says. “The rate of advancement in the technology is not going to slow down, so the next few years are going to be an incredibly exciting time!”

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