inside...

2 Innovation in Academia

5 Recent Publications

6 Intellectual Property at the CEM

6 Center for Exploration of Mountains

8 Seminar Series in Biomedical Science and Engineering

Massachusetts General Hospital55 Fruit Street

GRB 1401Boston, MA 02114

T 617.726.3474F 617.573.9471

ireis@sbi.org

FROM THE EDITOR Biju Parekkadan Biju_Parekkadan@gmail.com

Translational research has be-come integrated into the executive roadmap of academic departments, research centers/ institutes, and foundations across the country. Dr. Elias Zerhouni, Director of the National In-stitutes of Health, said “It is the responsibility of those of us involved in today’s biomedical research enterprise to translate the remark-able scientific innovations we are witnessing into health gains for the nation.” We at the CEM embrace this sense of duty within our academic research by creating new technol-ogy platforms that can be directly integrated into clinical medicine.

In this issue, we focus on translating academic projects into real-world products for health-care with a feature piece on innovation within the academic biotechnology sector. Robert Granier, Director of Business Development at Massachusetts General Hospital, brings unique insight into research from the perspec-tive of business development. He discusses how to evaluate a technology and outline stag-es of the cost structure and revenue stream of a new venture. This evaluation can come at a critical time in technology transfer from an academic institution to an industrial one. I will briefly discuss some of the evaluations that can take place in academia and how they can guide literature review and experimentation. These evaluation points will be revisited in a thorough due diligence analysis performed by parties that are interested in the technology.

A large chasm separates an initial laboratory finding in academia to an actual product to be used in clinical medicine. Often many tech-nologies can fail when traversing this chasm because objective criteria that can govern the future success of a product cannot be met. One of the first critical steps is the creation of broad intellectual property. This can some-times be challenging because at an early stage of discovery, the technology may be so embry-

onic that certain applications of the discovery have not been realized by the inventors them-selves. Here begins a working relationship with technology licensing offices at institutions and patent attorneys to guide this process and ultimately technology transfer. But the more “homework” that is done by the inventors, the smoother this process will be.

An invention is patentable if it is: (a) novel, (b) useful, and (c) non-obvious. Non-obviousness is the essential aspect to emphasize: is there any prior art that would have prompted the skilled person to modify or adapt said prior art to achieve what one is claiming? At this stage a thorough prior art search by the inventor can often uncover important points about the dis-covery that should be highlighted in the claims of a patent application. These claims should be product-driven; that is, each claim should be geared towards preventing others to make a product that is similar to your own.

Since an important aspect of academic re-search is to disseminate information quickly to fuel further independent innovation, a pro-visional patent application is often warranted to protect international rights during public disclosures of data (e.g. conference presen-tations) prior to a full utility application. A provisional application allows the inventors one year to validate the claims within the ap-plication, with impunity over other competing applications submitted after that priority date. This validation process is essentially an ex-perimental plan to be executed over the next year. This one year period is also an excellent time to procure new funding for advancement of the project.

Perhaps even more important to an invention being patentable, is the question of freedom to operate. Freedom to operate refers to other competition in the field that will limit the abil-ity to freely execute your patent claims without infringement. These competing patents can be barriers to commercialization of a technol-ogy and therefore, structured licensing agree-ments may be necessary to avoid potential

1

CEM CommuniquéCenter for Engineering in Medicine Newsletter

Win

ter

20

08

v.6

.2

For previous editions of the CEM Communique, please visit http://cem.sbi.org/about-publications.htm

NEW MEMBER PROFILE Robert Bieganski joined the Metabolism, Transplantation, and Stem Cells research group at the CEM in September 2008. Robert received his Ph.D. in Biological Chemistry from MIT where his training centered on organic synthesis and spectroscopic analysis of a large number of synthetic peptides designed to form structured beta-sheet models in cryoprotective solutions and dimethyl sulfoxide. His research at the CEM is currently focused on identification of novel compounds that rapidly promote lipid clearance from cultured fatty hepatocytes. In his free time, he maintains the research web site of his former supervisor with the home page at the URL: http://lansbury.bwh.harvard.edu/.

The Cash Curve: A Tool for Innovators Robert Granier, Director, Business Development, Massachusetts General HospitalFor info regarding the featured article email rgranier@partners.org

Managing innovation presents a tremendous challenge to organizations and individual entrepreneurs. Success requires a disci-plined approach, analytical tools to guide decision making, and planning so that projects are aligned with outcomes and resources. The cash curve, a financial model used to assess the profitability of projects, provides the framework necessary to help make in-novation successful.

The cash curve in Figure 1 provides a storyboard for innovation. If the net cost (revenues generated less costs incurred) of develop-ing and commercializing a new technology is plotted over time it will appear similar to the graph shown.

Following the graph from left to right, we see that before resources are committed to a project it is evaluated for technical and financial merits. This “scoping” phase is a simple and quick analysis that consists of defining the applications and tar-get markets of the technology. For those applica-tions that warrant a closer look, a comprehensive business analysis is performed in which product requirements and commercialization strategy are defined. This initial due-diligence process uses the following four criteria to determine the prob-ability of a successful outcome:

Market AttractivenessThe three most important factors that determine a market’s attractiveness are size, growth and profitability. Together, they will predict the up-ward climb to break-even and the total payback of a project.

2

$

T

Product life-cycle StagesProduct Development Stages

Market Introduction

GrowthMarket

MatureMarket

SaturatedMarket

Scopin

g

Business

Case Development Testing &

Validation

“The Hole”

1st

2nd

3rd mezzanine

IPOVenture CapitalMergers & AcquisitionsStrategic Partnerships

Venture CapitalStrategic PartnersFriends and FamilyAngelsGovernment Funding

Break-even

Patent terms end andcompetitive products enter market or disruptivetechnology enters market

CommercialLaunchSPEED SCALE

Figure 1. The cash curve is a derivation of the payback period concept used frequently in finance to evaluate a projects viability. The graph plots the net cash (Y) spent on a project over time (X). For the purposes of this article, net cash is equal to revenue generated less money spent, however non-investment cash is excluded. While it provides critical information for planning and developing a strategy for technology development, it does not take into consideration risk or the time value of money, which is left to subsequent analysis (Discounted Cash Flow model).

The illustration in this figure is a hypothetically example in terms of the cash flows, temporal aspects of funding, and the patent window.

TECHNICAL RISK MARKET ACCEPTANCE RISK

infringement. As a general rule of thumb - the more competi-tion, the less appealing the technology may be to investment. Certainly, an intellectual property plan can even be considered in academic settings in order to create “portfolios” that can be licensed individually or as a package to interested parties.

Although intellectual property is designed to cover many differ-ent applications, at this next stage a focused plan to reduce the concept to practice for the “killer application” within the frame-work of academic research should be the priority to generate significant interest to the licensee. Depending on the technol-ogy, this could involve studies to define a mechanism of action, prototype creation, and/or the first iteration of a standard operat-ing procedure. If appropriate, regulatory paths should be cross-referenced at this point to determine if experimental methods are in-line with a country’s safety policy for a technology. Opti-mization and manufacturing studies should be considered, but are not typically performed in academic settings. These consid-erations, amongst many others, can be passed on to the next generation of product developers.

A clear market analysis can be helpful to the academic re-searcher in order to understand the economic constraints that may actually affect the way one would design experiments. For example, if a technology is being developed for a global health effort the raw materials for this technology, used even in the in-ventor’s laboratory, should be inexpensive and robust. If the inventors themselves have interest in licensing the technology, then additional considerations including corporation develop-ment, pertinent milestones, and a financing plan should also be made. This financing plan should coincide with major inflection points in the business development. Also, conflicts of interest must be monitored if businesses are spun out of academic labs. In our feature, we’ll go into detail with some of the foreseeable costs and how these costs themselves may be a “fight or flight” situation for a new start-up.

Here at the CEM, our goal is to create the next generation of bio-engineered products and we hope to be an example of a cross-disciplinary approach that not only involves interactions between physicians, scientists, and engineers but also legal and financial consultation to work together towards this healthcare mission.

Market size, the measure of demand in units, is most revealing when it is used with the product’s price point to determine the total market value. Referencing Figure 1, it is important that a market’s value is capable of overfilling the financial hole it will dig during the pre-launch phase of the venture. Investors in the technology are interested in their return on investment and often use market size as a gating factor. Typically, high-end ven-ture capital firms only consider projects that are chasing markets worth at least $500M or tens of billions of dollars in the case of more expensive and risky investments such as pharmaceu-ticals.

Market growth, calculated as the compound annual growth rate (CAGR), is used to determine how stable the market is and how badly a product is needed. The latter refers to slope of the cash curve after the product launch. Another potentially attractive characteristic of high growth markets is that they are often char-acterized by emerging sales channels, whereas in mature mar-kets, sales and distribution networks have established strong relationships with existing product lines. In mature markets a CAGR of 2-10% could be considered healthy, however for young markets a CAGR in the 15-30% and beyond typify strong mar-kets. Both market size and growth rates are usually available from a variety of market research firms.

Profitability is a key indicator of a product’s ability to fund growth and ultimately attract buyers. Attractive gross profit margins in life sciences exceed 50%. Determining profitability can be a dif-ficult task, particularly with new products in unfamiliar markets. In some cases product analogies and business cost structures can be extracted from industry case studies or financial reports. If a good model isn’t available, the pro-forma financial analysis can be compiled from raw information provided by suppliers and contract manufacturers.

Competitive EnvironmentMarket fragmentation, competitive products, and barriers to en-try make up the competitive environment of a given technology.

A highly fragmented market is characterized by a variety of pro-ducers and consumers each with many different products and needs, respectively. A notorious example is the in vitro diagnos-tics market where there are hundreds of products that are fur-ther fragmented by combinations of tests and testing methods. A good example of a product in this type of market is glucose testing. Glucose tests can be fragmented based on different consumer needs: an emergency room physician or nurse has different requirements than those of a primary care physician or a patient using the test at home. This can complicate product development and significantly increases the costs of commercial scale-up. A high degree of fragmentation often means that the market is highly competitive with well established brand names that can be difficult to compete against. However, in some in-stances, investors may like these markets if they believe a new technology can consolidate some of the customer fragments.

Few products enter markets where there is no competition (if you think you’ve found one, look harder). Even if there is no competition at the time of the discovery chances are there will be at least one by the time you launch the product. There is also the potential scenario of counterfeit products to consider,

which ultimately leads to the development of trade secrets and further intellectual property development. Knowing when and how these competitors will influence the market can play a criti-cal role in formulating product development, scale-up and exit strategies.

While every market has certain hurdles that must be overcome few, if any, have as many as the medical technology sector. The immediate effect of these barriers is that they protract develop-ment and thwart commercial scale up. Regulatory compliance, for example, can take anywhere from a few months in the case of a simple non-invasive medical device to a decade or more for drug development. The amount of time and work required to meet these standards increases the cost side of the cash curve and make funding much harder to secure. Most barriers can’t be avoided; the strategy for dealing with them is to understand them and incorporate them into the strategic planning process.

It is important to mention here that the single most important strategy for dealing with competitive threats is intellectual prop-erty protection. As the technical experts in the field of their in-vention, inventors should take the lead role in developing the technical scope of the document. Intellectual property must be managed carefully because investors will look at the strength and breadth of the intellectual property when considering mak-ing an investment.

Feasibility Feasibility evaluates the inherent technical risk associated with a technology’s ability to produce a viable product. At one extreme is drug development where hundreds of hits for a target may re-sult in just a few lead compounds, most of which will never make it through pre-clinical trials. The feasibility study of the technol-ogy breaks down the development and scale-up processes into discrete high level tasks with specific goals and evaluates the likelihood of meeting each goal.

Profitable exitFew projects are developed without the contributions of inves-tors of one sort or another. Stakeholders and will be rewarded for their contributions (including the inventor). In some cases a preferred exit strategy drives how resources are obtained, but more often than not securing resources drives the exit strategy. Investors must have a way to “cash out” of their investment, usu-ally preferring merger, acquisitions or initial public offerings. The value extracted from either strategy varies greatly depending on the type of business as well as the general state of the economy and trends in the industry.

How well do these criteria correlate to a successful venture? This depends on how one defines success. Success is most often associated with, and measured by, profitability. But there are other measures of success that are dependent on the per-spective of the individuals involved in the venture.

When outside investors are brought in, they assess the criteria and can influence the execution odds of a venture by what they bring to the table. While each investor is different, most stick to the referenced values mentioned above for these criteria. There are, of course, exceptions. Social venture capital firms use a “double bottom line”* valuation technique that considers

3

4

the social impact of the product or service as well as the return on investment. A low cost AIDS/HIV diagnostic is an example of a technology that would align well with a social venture capital firm. Furthermore, as discussed briefly below there are ways - some emerging - to minimize the cost of innovation and as a re-sult the amount of capital required. Doing so changes the rules of the game a bit and opens up the doors to less profitable, but commercially viable, projects.

In a fundamental sense, just because a project won’t attract ven-ture capital hardly means that it can’t succeed. To most venture capital investors, a large return in a 3-5 year timeframe (or less) is considered a success, but an individual entrepreneur may not care about early liquidity, and they definitely don’t require a re-turn large enough to pay for nine investments that failed.

Perhaps the most essential, yet immeasurable, criteria that is highly correlated with any form of success is a knowledgeable, cohesive, and dedicated entrepreneurial team that can gener-ate sufficient capital to execute a strategy despite making a few mistakes along the way.

After a project is vetted by all the stakeholders, resources are allocated to the product development process and the cash curve begins its decent. The iterative development process will take several cycles to produce a prototype appropriate for pre-market testing and validation. The time and cost of taking a project through these stages will define the downward slope of the curve and is highly dependent on the quality and quantity of resources available. At the time of the product launch, the focus of the business shifts quickly from product development to sales and marketing.

James P. Andrew and Harold L. Sirkin of the Boston Consulting Group point out that there are four factors that influence the cash curve. Namely, they are start-up (pre launch) costs, time-to-market (speed), support (post launch) costs, and time-to-volume (scale) [1]. These four factors provide the basis for cash curve analysis which in turn can help an innovator plan for the resourc-es required to get their company to a stable, cash-flow positive position.

Start-up CostsStart-up costs, also referred to as pre-launch costs, stem primar-ily from the product development activities introduced previously and include resources such as the facilities, staff, equipment and supplies necessary to transform a concept into a product. In Figure 2(a) the cash flow profiles of a project with different pre-launch costs is compared.

There are a variety of opportunities for entrepreneurs within aca-demic medical centers to lower the burden of start-up costs on a new venture. Money that doesn’t have to be paid back, referred to as non-dilutive funding, reduces the lowest inflection point on the cash curve. Two well known sources of funding from the federal government are SBIR and STTR grants that are availabe though the departments of defense, homeland security, agricul-ture and NASA all have funding available for a variety of technol-ogy projects as well. At MGH, the Partners Healthcare System, CIMIT and the Partners Venture Fund provide various levels of funding, though the latter is actually a venture capital fund that

retains a portion of the new company’s equity. Strategic industry partnerships and foundations can also be considered, though they require some stake in the technology.

When start-up costs are reduced technologies reach net profitabili-ty sooner, a larger percentage of the equity is retained by the inven-tor and start-up team and funding sources are more accessible.

SpeedSpeed is the time it takes to get from an idea to a marketable product. Figure 2(b) shows how time-to-market impacts a proj-ects overall profitability. Speed reflects the inherent technical risk of the development process as well as the quantity and quality of resources that are allocated to the pre-launch activities.

Speed is particularly critical where technologies are protected by patents. Although underestimated when compared to full-blown industrial research and development, internal product de-velopment at academic medical centers has many advantages over the industry equivalent. There are a variety of ways that these centers can leverage existing resources to accelerate the innovation process such as utilizing the seamless interface with the consumers to define demand and product requirements, accessing research and clinical resources to conduct trials, and tapping an academic network that transcends institutional boundaries. While it is unlikely that academic medical centers will ever be able to compete with the financial resources that an industrial enterprise can dedicate to a single project, there are other intangible assets that are prevalent in academic medical centers. These include branding, an expanded knowledge pool, and future exclusive licensing opportunities.

Support CostsSupport cost is the cash used to generate revenues. The effect of these cash flows on the net costs that make up the cash curve is demonstrated in Figure 2(c). Much like undercapitalized devel-opment and speed, when insufficient capital is allocated during the post-launch period commercial scale up suffers and market value is lost. Because operations typically make up the bulk of support costs, operations efficiency is their primary driver.

The Cash Curve in Action

Figure 2(b)

LOSSES

If time-to-market (speed) is compromised due to insufficient resources losses result.The trade-off between reducing pre-launchcosts and speed should always be considered.

Figure 2(a)

GAINS

When an organization leverages existingresources such as facilities and knowledge, the pre-launch costs are reducedand financialgains are realized.

Figure 2(a)

If time-to-volume (scale) is sacrificedbecause growth funding is limited any gainsrealized from reduced post-launch costs may be lost.

Figure 2(d)

LOSSES

Figure 2(c)GAINSFigure 2(c)

A reduction in the net cost required todevelop market volume can result in a gainin profitability. Post-launch cost gains can berealized by developing efficient distributionand sales channels.

Within operations, there are six factors that contribute to most of the support costs: the financing, supply chain, production, the distribution, sales and marketing. In addition to access to capi-tal, efficient operations are a function of the business structure and the management team. While this article focuses primarily on the pre-launch phase of innovation, forward-thinking entre-preneurs actively network in order to build a management team around them that can help build up the business after the com-mercial launch.

ScaleThe last factor that helps shape the cash curve is the rate at which a product supplies demand. The time it takes a product to reach its market volume, called scale, reflects the market acceptance risk of the technology. Scale has the same effect on the cash profile as speed (Figure 2(d)). In some cases, when a product is aligned with the hospitals services, product commercialization within the hospital is a viable option. This partnership can aid in-fluence scale by having a highly reputable medical center become the first large-scale customer’s of the technology. The Circulat-ing Tumor Cell (CTC) Chip developed at the BioMEMS Resource Center and designed to capture CTCs from cancer patients using a microfluidic device, is one example. Once a validated product, it is possible that local hospitals can offer this diagnostic service to patients allowing the hospital to become a -test site and potential leader in cancer diagnosis and treatment.

If there is one thing to take away from this article it is the big pic-ture about innovation that is illustrated by the cash curve. The cash curve is a pragmatic model that academic medical centers can use to reassess their approach to innovation and expand their role in the communities they serve. It is also a tool that threatens to discipline creativity with the challenge of plotting its course. Having an idea about what waits at the end of the in-novation process is just the beginning. At an absolute minimum, the exercise of thinking through the cash required to proceed through all phases of the cash curve will provide the innovator with increased perspective on the market potential of their tech-nology and insights into key sensitivities in their commercializa-tion model.

*The double bottom line refers to the financial term “bottom line” or net profit. The second bottom line refers to the social im-pact.

Reference:

Andrew, James P. and Sirkin, Harold L. Payback. Boston: Har-vard Business School Press, 2006

5

RECENT PUBLICATIONS Radial flow hepatocyte bioreactor using stacked microfabricated grooved 1. substrates. Biotechnol Bioeng 2008; 99: 455-467.Equilibrium separation and filtration of particles using differential inertial 2. focusing. Analytical Chemistry 2008; 80: 2204-2211.Detection of Mutations in EGFR in Circulating Lung-Cancer Cells. New 3. England Journal of Medicine 2008; 359: 366-377.Desiccation Kinetics and Biothermodynamics of Glass Forming Trehalose 4. Solutions in Thin Films. Annals Biomedical Engineering 2008 May 24. [Epub ahead of print].Cell-cell interaction modulates neuroectodermal specification of 5. embryonic stem cells. Neuroscience Letters 2008; 438(2): 190-195.Vitrification by ultra-fast cooling at a low concentration of cryoprotectants 6. in a quartz micro-capillary: a study using murine embryonic stem cells. Cryobiology 2008; 56(3): 223-32.Molecular Reproduction and Development 2008. [Epub ahead of print]7. Elastomeric microchip electrospray emitter for stable cone-jet mode 8. operation in the nanoflow regime. Analytical Chemistry 2008; 80(10): 3824-31.Enhanced differentiation of embryonic stem cells using co-cultivation with 9. hepatocytes. Biotechnol Bioeng. 2008 Jun 2. [Epub ahead of print]Microfluidic leukocyte isolation for gene expression analysis in critically ill 10. hospitalized patients. Clinical Chemistry 2008;54(5):891-900. Invention, innovation, entrepreneurship in academic medical centers. 11. Surgery 2008;143(2):168-71.A microfluidic bioreactor for increased active retrovirus output. Lab Chip 12. 2008; 8: 75-80.Microfluidic flow-encoded switching for parallel control of dynamic cellular 13. microenvironments. Lab Chip 2008; 8: 107-116.The use of elastin-like polypeptide-polyelectroliyte complexes to control 14. hepatocyte morphology and function in vitro. Biomaterials 2008; 29: 625-632.Homogeneous differentiation of hepatocyte-like cells from embryonic 15. stem cells. FASEB J 2008; 22: 898-909.Isolation rearing impairs wound healing and is associated with increased 16. locomotion and decreased immediate early gene expression in the medial prefrontal cortex of juvenile rats. Neuroscience 2008; 151: 589-603.Burn-induced immunosuppression: attenuated T cell signaling 17. independent of IFN-{gamma} - and nitric oxide – mediated pathways. J Leukoc Biol 2008; 83: 305-313.

Activin alters the kinetics of endoderm induction in embryonic stem 18. cells cultured on collagen gels. Stem Cells 2008; 26: 474-484.Three-Dimensional Primary Hepatocyte Culture in Synthetic Self-19. Assembling Peptide Hydrogel. Tissue Eng, 2008; 14: 227-236.Identification of regulatory mechanisms of the hepatic response to 20. thermal injury. Computers and Chemical Engineering, 2008; 32: 356-369.Informative gene selection and design of regulatory networks using 21. integer optimization. Computers and Chemical Engineering, 2008; 32: 633–649.Functional modulation of ES-derived hepatocyte lineage cells via 22. substrate compliance alteration. Ann Biomed Eng, 2008; 36: 865-876.Mesenchymal stem cell-derived molecules directly modulate 23. hepatocellular death and regeneration in vitro and in vivo. Hepatology 2008; 47: 1634-1643.Cellular response to nanoscale elastin like polypeptide polyelectroliyte 24. multilayers. Acta Biomater 2008; 4: 827-837.A New Technique for Primary Hepatocyte Expansion In Vitro. 25. Biotechnol Bioeng [Epub ahead of print].Site-directed mutagenesis of the hinge peptide from the 26. hemagglutinin protein: enhancement of the pH-responsive conformational change. Protein Eng Design 2008; 21: 395-404.Bone marrow-derived mesenchymal stem cells ameliorate autoimmune 27. enteropathy of regulatory T cells. Stem Cells 2008; 26: 1913-1919.Sequential cold storage and normothermic perfusion of the ischemic 28. rat liver Transplantation Proceedings 2008; 40: 1306-1309.Augmentation of EB directed hepatocyte-specific function via collagen 29. sandwich and SNAP. Biotechnol Prog (in press).Mesenchymal stem cell therapy for protection and repair of injured vital 30. organs. Cell Molec Bioeng 2008; 1: 42-50.Steatosis revesibly increase hepatocyte sensitivity to hypoxia-31. reoxygenation injury. J Surg Res 2008, Jan 28 [Epub ahead of print].Gene expression profiling of long-term changes in rat liver following 32. burn injury. J Surg Res (in press). Selective targeting of pigmented retinal pigment epithelial (RPE) cells by a single pulsed laser irradiation: an in vitro study. Opt Express 2008; 16: 10518-10528.Enhanced differentiation of embryonic stem cells using co-cultivation 33. with hepatocytes. Biotech Bioeng 2008, June 2 [Epub ahead of print].

Transient gene delivery to differentiating embryonic stem cells for 34. recovery and functional enrichment of hepatocyte-like cells. Biotech Bioeng (in press).Computational studies of a protein based NanoActuator for 35. NanoGripping applications. Int J Robotics Research (in press)Moloney Murine Leukemia virus decay mediated by retroviral Reverse 36. Transcriptase degradation of genomic RNA. Virology (in press).Dissimilar hepatic protein expression profiles during the acute and flow 37. phases following experimental thermal injury. Proteomics (in press).

INTELLECTUAL PROPERTY CREATED AT THE CEM Cryopreservation of harvested tissue and cultured living tissues and 1. equivalents, US patent # 5,964,096Co-cultivation of cells in a micropatterned configuration. 2. US patent # 6,133,030Controlled reversible poration for preservation of biological materials, 3. US patent # 6,127,177 Ultra-rapid freezing for cell cryopreservation. US patent # 6,300,1304. Methods and devices for cell culturing and organ assist systems, 5. US patent # 6,562,616Cell culture systems and methods for organ assist devices, 6. US patent # 6,759,245Microinjection of cryoprotectants for preservation of oocytes. US 7. patent # 6,673,607Cell analysis and sorting apparatus for manipulation of cells. 8. US patent # 6,692,952Microfluidic cell lysis device and uses thereof. US patent application # 9. 60/414,065Cell depletion devices and uses thereof. US patent application # 10. 60/414,258 Microfluidic device for cell separation and uses thereof. US patent 11. application # 60/414,102.Plasma supplement and use in liver assist systems. 12. US patent # 2004005 (8309A1).Microfabricated elastomeric stencils for micropatterning cell cultures. 13. US patent application # 60/312,405.

Microfluidic systems for size based removal of red blood cells and 14. platelets from blood. US patent application # 60/478,299.Methods for prenatal testing and uses thereof. US patent application # 15. 60/420,393Device and method for contacting picoliter volumes of fluids. US patent 16. application # 60/478,277.Methods and compositions to preserve biomaterials with non-17. metabolizable bio-preservation agents. US provisional patent # 60/493, 616Systems and methods for cell preservation. US patent application # 18. 60/398,964 and 60/398,921Magnetic device for isolation of cells and biomolecules in a microfluidic 19. environment. Filed on March 3, 2004.System for delivering a diluted solution of blood from a sample 20. collection tube. Filed on March 3, 2004.Preservation of biomaterials with transported preservation agents. 21. International Patent Application #PCT/US04/25469Selection of cells using biomarkers. US Patent Application # 60/820,77822. Rare cell analysis using sample splitting and DNA tags. US Patent 23. application # 60/804,810Methods for the diagnosis of fetal abnormalities. US Patent application 24. # 60/804,817A microfluidic chip of CD4 + T cell count based on flow assisted cell 25. affinity isolation. US Patent application # 60/782,470.Biopreservation of cells by vitrication in a microcapillary at low 26. cryoprotectant concentration. US Patent application # 60/792,019 & 60/792,020.Devices and methods for magnetic enrichment of cells and other 27. particles. US Patent application # 11/323,971.Systems and methods for enrichment of analytes. 28. US Patent application # 11/229,332Methods, Compositions, and Devices for Treating Organ Failure. 29. International Patent Application # PCT/US2007/081142, 2007 November 10.Methods and Compositions for modulating immunological tolerance. 30. Provisional patent application # M0656.70163US00

6

NEW TO THE CEM Name From Group Robert Bieganski University of Virginia Metabolism, Transplantation, and Stem CellsCandice Calhoun Northeastern University Metabolism, Transplantation, and Stem CellsEric Yang Rutgers University Genomics, Proteomics, and Microsystems

RECENT DEPARTURES Name To Dino DiCarlo Assistant Professor Department of Biomedical Engineering, UCLAAman Russom Assistant Professor Department of Electrical Engineering, Royal Inst. of Tech., Sweden Herman Tolboom Surgical Resident Zurich University, SwitzerlandQing Song Research Associate Department of Chemical Engineering, MITIpsita Banerjee Assistant Professor Department of Chemical Engineering, Pittsburgh UniversityKazuhiro Suganuma Assistant Professor Department of Surgery, Keio University, JapanRonjun Research Scientist BD Biosciences, Boston, MAHalong Vu Research Scientist Monsanto Corporation, Cambridge, MAXianhong Cheng Assistant Professor Materials Science and Engineering, Lehigh UniversityNirpen Sharma Research Associate Department of Biomedical Engineering, Rutgers UniversityMonica Casali Research Associate Broad Institute

CENTER FOR EXPLORATION OF MOUNTAINS François Berthiaumefberthiaume@hms.harvard.edu

Every summer the “other” CEM organizes a big trip. This time it was a through-hike across the Sierra Nevada in southern Califor-nia. The plan was to follow the High Sierra Trail, a “classic” in the hiking world. This hike normally takes 7 days to complete, but we added a couple of extra days to allow for day hikes to summits along the way. This also provided more flexibility in case more time was needed to complete the trip. There were 4 participants: Francois Berthiaume, Carolina Cabral, Alex Revzin, and Harihara

Food Planning – Sea Level

Finally, we began the hike the next morning. The High Sierra Trail officially starts on the western slopes of the Sierra Nevada in Sequoia National Park, near popular tourist spots like the Sherman Tree, but most tourists don’t venture very far, so the crowds dissipated quickly once we hit the trail.

High Sierra Trailhead – 6700 ft

The first couple of days were strenuous since our packs were at their heaviest and we mostly had to go uphill. We went by pristine alpine lakes, and the vegetation gradually changed from pine forests to grassy tundra as we gained altitude.

It’s a Big Wilderness…

Top of the Pass - Kaweah Gap at 10700 ft

Signing the Summit Registry - Eagle Scout Peak

Approximately half-way on the trip, the trail went down in a U-shaped canyon where there were hot springs where we could relax. A nice break for our aching muscles! From there we head-ed further east, and as we made our way into the highest valleys in the park, vegetation became more scarce and the landscape changed to a world of rock gardens and steep rock spires. Soon, we could see the summit of Mount Whitney, the highest mountain in the continental US, although from where we were, it looked just about as high as New Hampshire’s Mount Washington! The Mount Whitney area is very popular among the locals, therefore we decided to venture off trail to set up our campsite. We found a beautiful lake just about a mile from the Trail, and we had the whole place to ourselves. From there, we did our most challeng-ing day hike, to Mount Russell, which has a knife edge summit with steep drops on all sides. A little scary… but what a view!

7

Baskaran, who was the organizer. After weeks of planning, we all got together on Friday August 8 in Southern California, shuttled cars between the end and beginning of the hike, and finished preparing our backpacks, as we had to carry along everything we needed, including food - with no possibility of resupply - for the next 9 days.

Arctic Lake Campsite - 12300 ft elevation

From the Top of Mt Russell

Then, we regained the main trail to hit the summit of Mt Whitney, which marks the end of the High Sierra Trail at mile 71, and from where we could look back at all the terrain we had covered. As we encoun-tered the crowds of day hikers that at-tempt to summit Mt. Whitney, we realized that we were not far from civilization.

Top of Mt Whitney High Sierra Trail Commemorative Plaque

Then, we then started a 10+ mile descent to the Whitney trailhead where we had dropped off our car. Our flight was leav-ing from Los Angeles, so we took a few minutes to stop at the beach for a quick swim in the ocean, and then hopped on our plane back home. All in all, it was a very rewarding trip!

2008 TRIP SCHEDULE

Before each trip, a description is sent to the “other CEM” e-mail list (if you would like to be added to this list, send a message to fberthiaume@hms.harvard.edu). These trips are open to anyone… Bring your friends along! For the rest of the year, we have a few more trips scheduled, which can be checked out on the website http://cem-outdoors.blogspot.com/.

September 26Sandra McAllister, PhDBiology, MITAction at a distance: systemic instigation of indolent tumor outgrowth

October 10Hidde Ploegh, PhDBiology, MITHerpes viruses as tools: glycoproteins and quality control

October 31Fil Swirsky, PhDRadiology, MGHIn vivo tracking of mononuclear cells to inflammatory sites

November 7Ken Rock, MDPathology, U Mass Medical SchoolThe sterile inflammatory response

November 14Carl Novina, PhDPathology, HMSNot miR-ly small RNAs: big biological roles for microRNAs in gene regulation.

December 5Alexa Kimball, MD, MPHDermatology, MGHClinical trials of early stage devices and drugs: how to get started and what to do next

December 19Ed Damiano, PhDBiomedical Engineering, BUThe role of the endothelial glycocalyx in cardiovascular health and disease

LOCATION: 4th Floor Conference RoomShriners Burns Hospital, 51 Blossom Street, Boston

TIME: Fridays 10:00 AM - 11:00 PM

Co-Sponsored by the Shriners Burns Hospital and Massachusetts General Hospital.

For more information,please contact Ilana Reis at 617-371-4882 or ireis@sbi.org

fall 2008 seminar

Biomedical Science

8