The Dolcera Blog

What’s Organ printing? What’s Bioprinting? Does organ printing really mean what it says in itself?? Pr-in-ting organs?  What do these technologies have to offer? What would the implications of these technologies be on the state of the industry, the general public and the entire humanity? Let’s just break the fourth wall here.  Who’s asking??

Well…To clarify, we are asking these questions in the interest of and to interest the general public and if the latter isn’t lost already (we earnestly hope that is the case) please read up…

Creating living tissue in complex geometries is a challenging issue facing the tissue engineering community.  Traditional tissue engineering techniques result in living tissue of simple, often 2D geometries.  By harnessing the capabilities of Solid-Freeform Fabrication (SFF) – also known as Rapid Prototyping (RP) –living tissue of arbitrary 3D shapes can be created directly from computer-aided design (CAD) data.

Bio-printing is a variant of 3D printing and can be defined as computer-aided, automatic, layer-by-layer deposition, transfer, and patterning of biologically relevant materials.  It is also known by other names such as “computer aided tissue engineering” and “biofabrication”.  In simpler words, bioprinting involves printing devices that deposit biological material.

Organ printing is a variant of bio-printing aiming at producing 3D organs. This is among the most promising advances of regenerative medicine. The 3D- Bioprinter was listed among the TIME magazine’s 50 best inventions of 2010. Most of the 3D printers use a modified version of inkjet printers to deposit dots of “bio ink” (cell suspension with 10 to 30 thousand cells per drop) that coalesce to form layers of organ interrupted by layers of biopaper (hydrogel mimicking the microenvironment of tissue) which is water-soluble.

Fig1:- Step-by-Step process of Organ Printing [1]

 

 

Roadmap to Bioprinting

Fig 2:- Roadmap to Bioprinting [2]

The 3D bioprinters currently in the market are produced by envisionTEC, Organovo, Tengion, Sciperio, Neatco, etc.

The NovoGen MMX 3D Bioprinter, priced at $200,000, has been developed by Organovo, a company in San Diego that specializes in regenerative medicine, and Invetech, engineering and automation firm in Melbourne, Australia. One of the founders of Organovo, Gabor Forgacs from the University of Missouri, Columbia, says the logic behind applying 3D printing for producing biological organs is “Although morphogenetic processes are under strict genetic control, genes do not create shapes and forms: physical mechanisms and processes do.” Organovo announced the production of first fully bioprinted blood vessels in Dec 2010. [3]

Organovo’s only real competitor, Tengion, holds most of the patents and legal rights to exploit the technology developed by the most successful bio printing scientist to date, Dr. Anthony Atala. Dr. Atala’s lab has grown a variety of human parts including blood vessels, heart valves and bladders, all using bio printing. Based on the same 3D print technology that Organovo uses, Tengion’s prototype printer has already produced several bladders which have been successfully transplanted into humans.

The 3D Bioplotter is produced by German company envisionTEC is a German company producing a range of 3D bioprinters such as 3D Bioplotter, E-Dent (Digital Dental printer), etc.  The 3D Bioplotter is priced at $188,000 and currently used in various laboratories to create various tissue scaffolds. [4]

Work of other research groups on Bioprinting:-

Boland and his coworkers from Clemson University have been producing Bioprinters since 2004.

VAXDesign of Sciperio Inc has a pressure operated 3D Bioprinter with four nozzles in the market.

Roland, Fishman, and Neatco collaboratively produce a pressure operated 3D Bioprinter with two nozzles. [1]

Professor Nakamura from the University of Toyama is currently working with Epson to produce 3D Bioprinters.

Sangeeta Bhatia from MIT together with Jennifer West from Rice University bioprinted living 3D liver constructs using stereolithography.

Tsinghua University group in China also printed liver construct using chitosan-collagen hydrogel.

A research group at Cornell University bioprinted living cartilage construct. [6]

The Bioprinting community meets annually at the International Conference on Bioprinting and Biofabrication. The next conference (the sixth) is to be held in Toyama, Japan in October 2011.

Future and Implications:-

Professor Vladimir Mironov, Director of Medical University of South Carolina(MUSC) , Bioprinting Center says that it would probably take an investment of  $1 billion to print living human organ suitable for clinical implantation.

Also, Dr. Atala says in vivo bioprinting i.e.; bioprinting right into a patient on the site of injury is very much feasible.

As Chair of The Department of Surgery of Stanford University and a leading expert in surgical innovation, Krummel recently wrote: “There is no such thing as a science fiction. There is only science eventuality”. [1]

Here’s to a future when Organ transplantation is hassle-free, affordable, automated, and customized.

Sources:-

1.       http://accessscience.com/content/Tissue-and-organ-printing/YB060455

2.       http://organprint.missouri.edu/PDF/HowToPrintOrgan-slides.pdf

3.       http://www.economist.com/node/15543683?story_id=15543683&subjectID=526354&fsrc=nwl

4.       http://www.envisiontec.de/index.php?id=8

5.       http://www.rapidtoday.com/future.html

Written by:

 Ajay S and Jnanasiddhy

Tweet  Delicious  Digg  Facebook 

A simple blood test and there you go….your complete health profile!

Or are you worried about a family cancer history?

The benefit of early diagnosis of such a deadly disease is obvious. The answer is the Wellness Chip®.

Researchers at Somalogic, Inc. have developed a diagnostic technology with high sensitivity and specificity. The Wellness Chip, the brainchild of Larry Gold and his colleagues at Somalogic, will bring together diagnostic tests for various diseases in a single, simple blood test. Currently, Somalogic has licensed its technology to Quest Diagnostics for launching a lung cancer blood test before the end of this year.

What is the Wellness Chip?

The underlying principle is nucleic acid-aptamer based proteomic technology. Somalogic’s proprietary reagents called SOMAmers (Slow Off-rate Modified Aptamers) are single strand stretches of modified nucleic acids generated by a highly selective process called SELEX (Systematic Evolution of Ligands by Exponential Enrichment). SOMAmers are capable of binding specifically to a target of interest, e.g., a marker for a particular disease. SOMAmers to various targets are fabricated on a chip at distinct positions and simultaneously detect several proteins in micro-liter scale samples. This data will then be analyzed by bioinformatics tools.

Contrary to conventional antibodies based diagnostic procedures, SOMAmers are more sensitive and specific and can be made rapidly in weeks rather than months as is the case with antibodies. It will also be economically priced -$100’s not $1000’s.

Why blood test?

Proteins present in the blood are immediate indicators of a person’s state of health.  Diseased tissues secrete proteins in the blood and their identification is essential to early and accurate therapeutic and preventative measures. The total number of blood proteins is about 4000 and the Wellness Chip can detect 1100 of these blood proteins. This protein profile will be analyzed to determine the health status of the individual. Currently available methods detect only about 20 to 30 proteins at a time.

From the laboratory to the market-

The SOMAmer technology has already found its clients in the pharma industry. In 2008, Somalogic entered into research collaboration with Otsuka Pharmaceutical Co., Ltd. for the development of diagnostic tools and to further Otsuka’s research in pharmaceuticals. On the other hand, the task of making the Wellness Chip a reality is entrusted with Quest Diagnostics.

Sources:

1.      http://www.somalogic.com/

2.      Bio.IT World.com. Turning blood into gold: The Wellness Chip

3.      http://www.colorado.edu/mcdb/goldlab/Slide%20Decks/8.%20Steve%20Williams%20slides.pdf

4.      U.S. Patent No. 7709192

5.      Gold L, Ayers D, Bertino J, Bock C, Bock A, et al. (2010) Aptamer-Based Multiplexed Proteomic Technology for Biomarker Discovery. PLoS ONE 5(12): e15004

6.      Ostroff RM, Bigbee WL, Franklin W, Gold L, Mehan M, et al. (2010) Unlocking Biomarker Discovery: Large Scale Application of Aptamer Proteomic Technology for Early Detection of Lung Cancer. PLoS ONE 5(12): e15003.

 

Written by:

Shweta Kumari

Tweet  Delicious  Digg  Facebook 

Mosquitoes are deadly little creatures troubling mankind since time immemorial. These are carriers of a deadly parasite responsible for the spread of Malaria- claiming millions of deaths worldwide. Despite enormous efforts to curb this disease, not much has been achieved and scientific communities are striving to come up with an effective defense mechanism. A new study led by Dr Flaminia Catteruccia from the Department of Life Sciences at Imperial College London, focuses on exploiting the reproductive mechanism of mosquitoes- a new dimension in malaria research.Interestingly, Anopheles gambiae, a species primarily responsible for transmission of malaria in Africa, mates only once in its lifetime. Scientists believe that interfering with mosquito reproduction could be a potential defense against malaria.  “In the fight against malaria, many hope that the ability to genetically control the mosquito vector will one day be a key part of our armory,” said Flaminia Catteruccia.

This could be achieved either by inhibiting the reproduction process or sterilizing the male mosquitoes by genetically modifying them to neutralize a gene required for sperm production.

In 2009 , research led by Flaminia demonstrated that knocking off a key enzyme called Transglutaminase results in an impaired mating plug, a coagulate of seminal fluid and proteins required to seal the male sperm inside female, and thus disrupts the reproductive process thereby providing a potential means to combat malaria.

Dr Catteruccia concludes: “If in the future we can develop an inhibitor that prevents the coagulating enzyme doing its job inside male A. gambiae mosquitoes in such a way that can be deployed easily in the field — for example in the form of a spray as it is done with insecticides — then we could effectively induce sterility in female mosquitoes in the wild. This could provide a new way of limiting the population of this species of mosquito, and could be one more weapon in the arsenal against malaria.”

Recently, a path breaking study (published in PNAS journal) reveals that genetically modified mosquitoes with inability to produce sperms mate successfully with the females as compared to the normal counterpart and crucially, this modification did not interfere with any other sexual function or behavior in either the female or the male, they explained in their study.

“Spermless males behave exactly like those with sperm,” Catteruccia says. “We saw no difference in their ability to compete.” She further added that releasing genetically modified, spermless male mosquitoes into the wild could in future help to prevent malaria transmission and reduce the chances of large outbreaks of the killer disease.

Furthermore, Elena Levashina who studies malaria carrying mosquitoes, a leading scientist at the Institute of Molecular and Cellular Biology in Strasbourg comments that “this is a crucial scientific demonstration and a huge step forward.”

This seemingly promising strategy to deal with outbreak of malaria is undoubtedly a major advancement and a potential weapon against malaria. However, these studies are in their initial stage and have been tested in field trials only and further experiments have to be done to use it on a large scale.

SOURCES:

Imperial College London. “Meddling in mosquitoes’ sex lives could help stop the spread of malaria.” ScienceDaily, 22 Dec. 2009. Web. 12 Aug. 2011.

Imperial College London. “Mosquitoes can’t spot a spermless mate.” ScienceDaily, 10 Aug. 2011. Web. 12 Aug. 2011.

Nature NEWS. “Female mosquitoes tricked by spermless males.” Published online 8 August 2011 | Nature | doi:10.1038/news.2011.467

Journal References:

1. Thailayil J, Magnusson K, Godfray HCJ, Crisanti A, Catteruccia F. Spermless males elicit large-scale female responses to mating in the malaria mosquito Anopheles gambiae. PNAS, 2011.

1. Rogers DW, Baldini F, Battaglia F, Panico M, Dell A, Morris HR, Catteruccia F. Transglutaminase-mediated semen coagulation controls sperm storage in the malaria mosquito. PLoS Biol. 2009.

Written by:

Abu Rafay

Tweet  Delicious  Digg  Facebook 

Tweet  Delicious  Digg  Facebook 

Tweet  Delicious  Digg  Facebook 

Ranking makes life easier. Be it top 10 companies, top 10 universities to study technology or to choose amongst top 10 sci-fi movies you want to watch on the weekends; ranking allow us to choose the best amongst the available. Time saver, decision influencer and extremely helpful are the ranked material.

At Dolcera, we thought of applying the ranking methodology to patents. We have ranked patents based on a variety of parameters. First factor amongst all remains the client focus, second, sufficiency of disclosed information in patents and third credibility of a patent to perform the same process/art with higher efficiency than any other patent with similar focus.

Let us consider an example, the first table in the image below show patents with similar focus of decreasing tumor volume using RNA interference (RNAi). The patent one has disclosed maximum information in this area and in addition to the desired data, it has also published a lot more supporting information derived from other experiments. Further, as the rank goes down the percentage decrease in tumor volume decreases. Some may argue that patent 2 has disclosed more decrease in tumor volume than patent 1 but then patent 1 has disclosed more supporting data, taking its overall weighted score higher. Of course, if the client is still interested only in comparing tumor volume, patent at rank 2 will come at rank 1. Hence the ranking is customized to suit the client requirements.

The ranking of patents is not that simple as it may sound. The analysis team has to encounter challenges and figure out the ways to overcome them. Graphs, charts, instrumental outputs etc. will not give you data in percentages which can be just copy-pasted to compare. They have to be calculated first using mathematical tools which may vary from calculating areas under the graphs or applying differentiation & integration on instrumental outputs, to allow the reader to compare results before making the final decision. It’s considered an absolute value add to the decision making process by the clients who have sought such a service from us.

Not all experimental data will be quantitative. For people familiar with biotechnology would know that there are experiments (such as gel electrophoresis, staining etc.) that give qualitative or quasi-quantitative results. I am sure, the same will hold true with other technology fields too. Second part of the figure above summarizes few patents which can not be ranked as there is no data yield from such experiments and hence comparison is not possible. But then why miss them? We provide a Dolcera summary table which will give reader an idea as these experiments were atleast conducted and disclosed in patents. This comparison will thus strengthen the decision to be taken from ranking matrices discussed above.

This systemic approach of collecting, sorting, analyzing, and finally ranking the data has the following advantages:

1. Saves time!
2. Easy comparative analysis.
3. Helps in competitive watch
4. Decision on in-and-out licensing can be made.
5. Strong baseline for future scientific investigations.

Who will be benefited?

Scientific community: Extensive experimental data, comparison matrix of data from different patents with same focus is a feast to researchers and scientists as it helps them to choose best technologies.

Patent attorneys: Allows competitor watch, supports their decision on in and out licensing.

Venture capitalists / investors: Patent ranking based on disclosed information helps investors to decide patents to further invest upon.

Which technology fields are covered?

Patents in all the technological fields can be ranked. You just need to tell us the focus area and we will rank the patents for you. The ranking and weighing scores can be customized to suit user’s requirements.

Tweet  Delicious  Digg  Facebook 

The discovery of RNA interference (RNAi) is one of the transforming events in biology. Gene silencing agents such as small interfering RNA (siRNA), micro RNA (miRNA) and small synthetic oligo-nucleotides (DNA, RNA or DNA-RNA complex) lead to target specific RNAi. We aim at building a one-stop comprehensive database of RNAi agents patented or described in scientific literature.Dolcera has provision to customize the database against the target gene suiting client’s requirement. Till now, RNAi agents against some of the important cancer target genes are updated to the database and the trial access is available on request. These genes include bcl2, myc (c-myc, n-myc), ras (k-ras, h-ras, n-ras), VEGF, STAT3 etc. RNAi agents can be extracted and added to the database based on client’s interest.

Dolcera RNAi database can prove helpful:

• For scientific community: RNAi agent sequences aligned to target genes, extensive experimental data and comparison matrix of data from different patents with same focus.  
• For patent attorneys: Competitor watch, assignee vs. number of publications graphs, timeline based on application and publication dates.
• For venture capitalists/ Investors: Patent ranking based on disclosed information, data useful for decision making.

Salient features of the database:

1. Interactive maps of taxonomy: 4 levels of in depth classification of patents and scientific literature allow both “bird’s-eye view” and “in-depth views” of technologies.
2. Patent and non patent dashboard: Grouping specific elements into more general categories is conceptually easier and cleaner than entertaining hundreds of specific elements separately. Dolcera dashboard has a friendly user interface. It groups the patents according to the taxonomy, patent numbers, publications and application dates at the click of a button.
3. Sequence Dashboard: The tool not only aligns all patented/ non patented siRNA/ miRNA sequences to the target gene but allow user to see the sequence related information on a simple click of the mouse.
4. Experimental matrix: Experimental data be it quantitative (eg. % inhibition of target mRNA expression) or qualitative (eg. gel blots) are compared amongst patent document with similar focuses. This allows users to compare literature with same focus. The ranking of documents can also be done based on scoring matrices, which allows user to read the most relevant patent first.

 For database related inquiries or free demo call us at, Phone: +1-650-269-7952 (US) and  +91-40-6451-0832 (India). You can also email us at info@dolcera.com

To read more about RNAi database click here

To visit Dolcera’s website and to explore more patent/ IP related services click here

Tweet  Delicious  Digg  Facebook