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MEMS IN THE MARKETBusiness Strategy Report

Group

25

M E M S I N T H E M A R K E T

Project Team

Name E-mail Backgrounds ResponsibilitiesRyan

DempseyRyan.d.dempsey@vanderb

ilt.eduBiomedical Engineering

Management of Technology

Business team leader Web site design

John Richardson

[email protected]

Biomedical EngineeringEconomicsBioMEMS

MEMS technology design team leader

Peter Shanahan

[email protected]

Biomedical EngineeringBioMEMS

Mathematics

MEMS technology design

Charles Bloom

[email protected]

Biomedical Engineering


Business team assistant Legal

Rachel Weaver

[email protected]

Biomedical Engineering


MEMS technology design assistant

Photography

Group 25 is composed of Ryan Dempsey, John Richardson, Peter Shanahan, Charles Bloom, and Rachel Weaver. The group was chosen based on a

combination of biomedical engineering and business backgrounds. Because the senior design project deals specifically with BioMEMS technology, it is our

mailto:[email protected]










intention to assemble a group with MEMS experience and biomedical engineering majors. Furthermore, the project includes a business portion,

which develops a strategy to market the MEMS device to venture capitalists. Initially, the group entered a business competition called the MRS Challenge, but the group did not qualify for entrance due to a lack of graduate business

students in the group.

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Table of Contents

MARKET DEFINITION..............................................................4MARKET SIZE....................................................................5STRATEGIC POSITIONING.................................................6

Benefits of pharmaceutical partnership.....................................7Current market demands...........................................................7Our “niche” in the market..........................................................7

CONSUMER PRICING.........................................................7Cost of maintenance...................................................................8

MARKET DRIVERS.............................................................8Cost and time savings................................................................8High-throughput screening (HTS)...........................................11Reagent conservation...............................................................11Reduction of human error........................................................12

MARKET BARRIERS.........................................................12Interfacing concerns................................................................12Lack of silicon flexibility..........................................................12Replacing old systems..............................................................13Lack of bioMEMS technological standard...............................13Government regulation............................................................13

BIOMEMS.........................................................................14INNOVATION SUCCESS FACTORS...................................15PRODUCT LIFE.................................................................15KEY MANUFACTURING CHALLENGES............................15COMPLEMENTARY TECHNOLOGIES...............................16

Microarrays..............................................................................16Microfluidic PCR......................................................................16

SUBSTITUTE TECHNOLOGIES........................................16LabChip....................................................................................16Lab-on-a-CD.............................................................................17High Performance Liquid Chromotography (HPLC) Chip.......17

FUTURE TECHNOLOGIES................................................17SAFETY, HEALTH, AND RISKS.........................................17KEY COMPANIES..............................................................19

Caliper Life Sciences...............................................................20

Cephoid....................................................................................20Agilent Technologies................................................................20Combimatrix.............................................................................20Nanogen...................................................................................21

GOVERNMENT POLICY....................................................22PATENT SEARCH.............................................................23INDUSTRY CONTACT LOG...............................................27FINANCIAL ANALYSIS......................................................29

Methods & Assumptions..........................................................29Pro Forma Profit and Loss Statement......................................29Project Recommendation.........................................................29

Executive SummaryThe objective of the “Business Strategy Report” is to create a business proposal in order to market our technology to venture capitalists. The long-term objective is to launch a start-up company based on our bioMEMS device. The following are the significant details covered in the report:

The market for our BioMEMS device includes companies involved in one of two related industries: (1) major drug manufacturing, and (2) drug delivery.

The market potential of bioMEMS devices is massive! One of the major customer requirements for our

technology is to effectively advertise our device to major pharmaceutical and drug delivery companies for approximately $3 per chip (beginning in 2008).

Our device will save an average of $1 million per year in reagent, labor, and disposal costs for every 10 assays

Combining strict regulation, the lack of a technology standard, and the conservatism of pharmaceutical companies, there are obvious barriers to market entry.

The following is a list of our device’s primary design innovation factors that improve on the most current designs:

o Circular wells to allow user-friendly cell insertion and perfusion

o Dual-chambers to allow independent experiments on a single chip

o Channel diameter is 100 micrometers to allow multiple cell perfusion

o Pico-liter volumes of reagento Disposable and low per-unit cost

Our device is disposable, thus the product life is equal to the length of a given experiment.

The future of our device’s design will be in bio-sensing. The top five companies (Caliper, Cephoid, Agilent,

Combimatrix, and Nanogen) account for approximately 48% of the total LOC market in 2004.

Our cell culture device is a Class I device regulated by the FDA. It is exempt from 510(k) pre-market notification and good manufacturing practices

The NPV of our project is $6,612,618 for the period between 2001 and 2010. Therefore, we should accept the project because it is profitable.

M E M S I N T H E M A R K E T – B U S I N E S S S T R A T E G Y

Market and Demand Environment “There is tremendous opportunity [in the bioMEMS market]” – Joseph Baron, PureTech Development

Market DefinitionThe primary market for our BioMEMS device includes companies involved in one of two related industries: (1) major drug manufacturing, or pharmaceuticals, and (2) drug delivery. The goal of our project team is to develop a device that can be sold to a major company in one of these two industries given the current demand for BioMEMS technologies. The pharmaceutical industry comprises companies primarily engaged in one or more of the following:

manufacturing biological and medicinal products; processing botanical drugs and herbs; isolating active medicinal principals from botanical drugs and

herbs; and manufacturing pharmaceutical products intended for internal

and external consumption in such forms as tablets, capsules, vials, ointments, powders, or solutions.

The drug delivery industry comprises companies developing systems by which therapeutic agents are introduced into the body, and directed in a controlled way towards a target organ or site of action. Conventional drug delivery forms are simple oral, topical, inhaled or injection formulations.

Note

Although our device could potentially be utilized in other areas of research, we have chosen to focus on the drug development and drug

Section

1

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delivery areas of the overall BioMEMS market. The primary reason for this is because these industries have the largest market potential over the next 10 years, as shown below.

Table 1 shows the leading pharmaceutical and drug delivery companies in terms of market capitalization. Currently, the top three drug manufacturing companies, by market capitalization, include Pfizer Inc., Johnson and Johnson, and GlaxoSmithKline. The top three drug delivery companies, by market capitalization, include Hospira Inc., Elan Corporation, and Biovail Corporation6.

Figure 1 displays all potential market applications for our microfluidic device. The primary applications for our BioMEMS device include high-throughput drug screening, clinical diagnostics, and genetic analysis. Our device will assist scientists by evaluating the effectiveness of a given drug to living cells.

Market SizeOur dual-chamber MEMS device has enormous market potential. BioMEMS is predicted to have the fastest growth rate within the entire MEMS market, particularly biomedical applications such as

Industry Company Symbol

Market Capitalization

Pharmaceuticals

Pfizer Inc. PFE $191.5 billion

Johnson & Johnson

JNJ $179.7 billion

GlaxoSmithKline

GSK $151.8 billion

Drug delivery Hospira Inc. HSP $6.5 billionElan Corp. ELN $6.0 billion

Biovail Corp. BVF $3.9 billion

Table 1. Leading pharmaceutical and drug delivery companies by market capitalization6

FIGURE 1. Markets for microfluidic devices1

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drug discovery and delivery. Figure 2 illustrates that BioMEMS applications will consist of approximately 16% of the entire $10.9 billion MEMS market. Figure 3 shows the large forecasted revenue growth of microfluidic devices from 2004 to 2012. The market is still emerging, and numerous companies are in the final stages of beta testing. The number of product introductions in 2006 should rise dramatically as compared with 2005.

2005 forecast MEMS markets by sector (total: $10.9 billion)

Automotive 41%Telecom 29%

Bio-med 16%Military 3%Other 11%

Source: Peripheral Research Corp, Santa Barbara, Calif.FIGURE 2. 2005 forecast MEMS markets by sector (total: $10.9 billion)

The following are various industry estimates for the BioMEMS market potential:

Research firm UBS Warburg estimates that the BioMEMS drug delivery market in the U.S. alone will go from $14.4 billion in 2002 to $28 billion in 2005. 4

NEXUS is predicting that the market for bioMEMS technology will grow to $19 billion by 2005.13

Yole Development research firm predicts that total sales in the MEMS market will increase from $3.85 billion in 2003 and grow to $7 billion in 2007. 9

John T. Santini, president of Microchips, Inc., estimates that the worldwide revenues for the drug therapy market will go from $20 billion in 1999 to $31 billion by 2004. 4

FIGURE 3. United States Microfluidics/LOC revenue forecasts 2004-20123

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Although the specific numerical estimates vary depending with whom one talks, one thing is clear: the market potential for BioMEMS devices used in drug development and delivery is massive!

Strategic Positioning Our primary objective is to market our bioMEMS device to major pharmaceutical companies. In order to do that, we must first create partnerships with various industry stakeholders. Figure 4 illustrates the stakeholder map of pharmaceutical and bioMEMS industries. BioMEMS companies are doing research in the area of drug delivery, diagnosis of diseases through lab-on-chip. As the field of operation for bioMEMS and pharmaceuticals is the same, it would seem that pharmaceutical firms would be actively seeking alliances with the new start-ups in bioMEMS technology.

Benefits of pharmaceutical partnershipThe linkage between BioMEMS and pharmaceutical companies could be equally beneficial for both industries, as it would increase the innovative output of pharmaceutical companies, and the start-ups could acquire the knowledge base or capital necessary to fabricate and test new devices. Control over these devices could lead to significant benefits in the marketplace. BioMEMS companies also help pharmaceutical companies in reducing product development cycle and increasing efficiency by reducing R&D costs.

Current market demandsAs with any emerging nanotechnology, the road to market penetration and profitability is extremely complicated. Currently, there are many companies attempting to gain market share in the BioMEMS market (see “Competitive Environment”), yet few have achieved profitability. In order for our bioMEMS device to have market success, a particular emphasis and effort should be placed on identifying the needs of our customers (i.e. pharmaceutical companies) and offering appropriate

FIGURE 4. Stakeholder map of pharmaceutical and BioMEMS industries11

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solutions. Among the most current demands given by major pharmaceuticals include1:

Cost efficiency Development of detection technologies (i.e. on-chip sensors) Interfacing micro and macro scales Reliable bonding metal electrodes onto polymer substrates.

Our “niche” in the marketThe key marketable feature that our device offers is the dual-chamber capability on a single chip. A dual-chamber bioMEMS device allows double the experiments to be performed on fewer chips, thus saving time and money. Furthermore, our device will also decrease labor costs and reagent costs, thus promoting cost efficiency. It is also our goal to also incorporate a Clark oxygen sensor onto our device in order to meet the demand of major pharmaceutical companies. This would allow one to detect cell metabolism in response to a drug. Finally, our device will utilize platinum working electrodes, and silver reference electrodes affixed to a stable polymer substrate. This meets the customer demand of utilizing reliable metal electrodes.

Consumer PricingOne of the major customer requirements for our technology is to effectively advertise our device to major pharmaceutical and drug delivery companies for approximately $3 per chip (beginning in 2008). Initially, the sales price will be much higher, approximately $5 according to our model in the “Project Valuation & Financing” section. The assay cost per randomly selected compound is approximately $5 per assay, which includes reagents, labor, and disposal costs. This cost will be reduced to $1 per assay by 2010. .Note

This unit cost estimate was suggested by Dr. Franz Baudenbacher of Vanderbilt University, assuming the device and its parts were manufactured in bulk. Please see Section 6 for more information on project financing.

Cost of maintenanceBecause our device is intended to be manufactured in bulk, the unit cost is minimized. Thus, the lower unit costs permit single-use disposable devices to be manufactured. This feature prevents risks associate with cross-contamination from re-use. Therefore, there are no maintenance costs involved with our device.

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Market DriversThere are a number of market drivers that will allow our bioMEMS device to achieve market success. The most important market drivers include:

Cost and time savings High throughput screening Reduction in sample size & conservation of reagent quantities Reduction of human error

Cost and time savingsCurrently, billions of dollars are spent finding “blockbuster” drugs by major pharmaceutical companies. Because of large amount of money that can be earned in the global healthcare market, these companies are spending more and more money on research and development (R&D) of new drugs. Despite rapid growth in outsourcing R&D activities over the last few decades, pharmaceutical companies have significantly expanded the number of their own employees devoted to the R&D of the company. Applying a real growth rate of 1.76% per year for compensation to a growth rate of 7.4% per year in employment yields a growth rate of 9.3% per year in labor costs for pharmaceutical companies. Given these labor costs, it would be in the best interests of a pharmaceutical company to save money on labor costs by utilizing new, more efficient technologies.

Major pharmaceutical companies spend an average of $802 million and 10 to 15 years researching and developing a drug to come to the market9. Comparing this to the 1987 average of $231 million and the 1976 average of $54 million, it is quite obvious that developing new drugs has gotten extremely expensive10. Figure 5 shows the trends in the pre-clinical, clinical, and total cost of an approved new drug. Table 2 illustrates the average cost out-of-pocket for clinical compounds at each phase of FDA approval. These estimates take into account the time value of money and inflation. Given the huge investment of developing a new chemical compound, only one out of five will ever make it to final

FIGURE 5. Trends in capitalized pre-clinical, clinical, and total cost per approved new drug9

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clinical usage7. Thus, there is much pressure within the companies to improve success rates, reduce cycle time, and lower R&D costs.

TABLE 2. Average out-of-pocket costs for clinical compounds by testing phase9

Our device features a dual channel capability on a single chip, which will allow for two simultaneous, independent experiments. This feature reduces the cost of having to perform experiments on separate chips, and it clearly saves time by allowing a single chip to be utilized in multiple experiments. Because of an increased hit rate, our device will have to screen less compounds in order to find an active compound. This saved time can be used towards the development of new drugs. Our device will also reduce reagent use because of its smaller dimensions.

We believe our device can improve data quality to the point where researchers can utilize data generated outside their laboratory or organization. This would improve productivity of the entire organization by reducing the need to

repeat experiments. An increase in productivity allows more work to be done per employee, thus the cost of researching and developing a drug decreases.

Cost Savings Calculation

Calculation Variables

Screening goal

Find 500 active compounds for further discovery efforts.

Current-hit rate

On average for randomly selected compounds you must test 1000 random compounds to find one active compound according to some threshold of activity.

Our device will save an average of $1 million per year in reagent, labor, and disposal costs for every 10 assays (see “Cost Savings Calculation” below).

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Assay cost per compound

Cost includes compound acquisition cost, reagents, labor, disposal cost, etc

NOTE: The following method for calculating cost savings is extremely crude due to a lack of access to current industry R&D budgets.

HTS with Current Method

Establish screening goal of 100 active compounds.

Order any 100,000 compounds.(Internal inventory or vendor.)

Screen 100,000 compounds to identify active compounds.

Expect 100 hits with present hit rate of 0.001.(100,000 compounds) x (.001) = 100 hits

CURRENT HTS COSTS FOR THIS ASSAY:

(# of compounds screened) x (assay cost per compound) = 100,000 x $1.50 = $150,000

Total cost: $150,000

Number of Hits: 100

HTS with BioMEMS

Establish screening goal of 100 active compounds.

Order any 10,000 compounds.(Internal inventory or vendor.)

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Screen 10,000 compounds to identify active compounds.

Expect 100 hits with present hit rate of 0.01.(10,000 compounds) x (.01) = 100 hits

HTS SAVINGS FOR THIS ASSAY USING BIOMEMS:

(# of compounds screened) x (assay cost per compound) = 10,000 x $5.00 = $50,000

Total cost: $50,000

Number of Hits: 100

Total cost using current HTS method= $ 150,000

Total cost using our bioMEMS device= $ 50,000

TOTAL SAVINGS FOR THIS ASSAY = $ 100,000

Yearly Return on Investment (ROI)

Total yearly savings for 10 assays = $1,000,000

Total yearly savings for 20 assays = $2,000,000

High-throughput screening (HTS)High-throughput screening (HTS), where millions of compounds are routinely assayed for activity against drug targets, is a fixture in every major pharmaceutical company in the world. These companies have reached a point where current bottlenecks can no longer be solved with existing products. Currently, drug discovery laboratories utilize miniaturized assays of 96-, 384-, or 1536-well plates. Our bioMEMS device will potentially increase HTS efficiency by doing two things:

Increasing the hit rate for randomly-selected compounds Reducing the number of compounds ordered for screening

Based on our cost savings calculation, we estimate that our device will increase the current hit-rate 10-fold from an average of one active compound for every 1,000 screened to 10 active compounds for every 1,000 screened.

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Note

The hit-rate estimate was made based on the hit-rates of similar products on the market today.

Reagent conservationOur device utilizes only a small fraction of the usual amount of expensive reagents used in experiments performed in test tubes, 96-well plates, 384-well plates, or 1536-well plates and also reduces labor involved in each experiment. Saving on reagent and labor costs can enable pharmaceutical companies to expand the scale of experimentation in ways that would otherwise not be feasible. Common reagent kits can cost as much as $4.28/sample12.

Caliper's LapChip technology, a bioMEMS technology similar to ours, utilizes approximately 1/5th of the enzyme and 1/100th of the substrate usually needed in experimentation. The dimensions of our device are 600 nm by 600 nm, with perfusion channels of 100 micrometers in diameter. The LabChip utilizes channels ranging from 10 to 50 micrometers in diameter. Because the dimensions of our device are among the smallest on the market today, we expect similar reagent consumption than currently used by Caliper’s chip.

Reduction of human errorMost non-reproducible results in clinical laboratories are a result of human error, primarily due to the large number of variables involved in manual experiments. Out bioMEMS device has the ability to repeatedly conduct experiments in a uniform manner, thus increasing reproducibility. This presents a major advantage over current methods. Experiments can be extremely expensive, thus a decrease in the number of overall experiments will decrease total cost considerably.

Market BarriersAdapting BioMEMS technology will not be a smooth road. Typically, medical applications require a long sequence of trials followed by government approval (see “Economic & Policy Environment”). According to Robert LeFort, president of Infineon Technologies, "only one out of 5,000 attempts gets to the commercialization stage and even then, they are only effective 50 percent of the time." 5 Combining strict regulation, the lack of a technology standard, and the conservatism of pharmaceutical companies, there are obvious barriers to market entry. Among the most prevalent barriers to market entry include1:

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Interfacing concerns: micro- versus macro- Lack of silicon flexibility Replacing old systems with new technologies Lack of BioMEMS technological standard Government regulation

Interfacing concernsThere are some concerns about interfacing macroscopic designs onto a micro-scale chip. A key feature of semiconductor manufacturing over the past 30 years has been its ability to produce ever smaller features. Because precision during micro-scale manufacturing is essential, every machine and calculation is extremely sensitive to error. For example, during the initial food coloring test for our device following fabrication, the initial batch of 5 devices proved to be faulty. Thus, we were forced to make 10 more to correct our manufacturing flaws.Lack of silicon flexibilityMEMS research to date has been dominated by silicon, and this situation is likely to continue for the foreseeable future. Silicon is an attractive material because of its low cost and high quality, its useful electro-mechanical properties, and the possibility of monolithic integration with electronics. However, silicon micromachining processes, while clearly able to produce an enormous range of useful MEMS devices, do have their limitations. Firstly, they are based on a very limited range of materials, whereas MEMS devices call for much broader materials. Silicon processes are also poorly suited to the realization of 3D structures.

Replacing old systemsThe conservatism of major pharmaceutical and diagnostics companies is a well-known fact. According to Joseph Baron of PureTech Development, the pharmaceutical industry is reluctant to “plow a lot of money into bioMEMS as the next big thing.” Though these companies may be skeptical implementing new systems, doing nothing is not an option for them. Baron says the industry either “has to deliver health benefits much more cheaply or make R&D vastly more productive.”

Lack of bioMEMS technological standard Another complication faced by companies seeking to develop BioMEMS devices is that BioMEMS lacks a technological standard, which would stabilize the development of new products. According to Jeeseong Hwang at the Optical Technology Division of the National Institute of Standards and Technology, BioMEMS must have a standard platform if it wishes to succeed. He says, “I am convinced

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that there will be a great thrust toward development of BioMEMS platforms (in the next couple years).”5

Government regulationPlease see Section 4: Economic and Policy Environment for information.

Technological Environment“It’s a great time to be thinking about how to do therapeutic devices. Anything is being considered a drug platform.”

- Michael Cima, MEMS professor at MIT

BioMEMS

A lab-on-chip (LOC) device is a micro-scale laboratory utilizing a network of micro-channels, electrodes, sensors, and electronic circuits. 3 BioMEMS, a type of LOC, are bio-functionalized microelectromechanical systems (MEMS) that are designed for usage in biomedicine and bioengineering. The term MEMS was created in the late 1980s to develop sensors and actuators out of the basic integrated circuitry micro-fabrication technologies, utilizing silicon as

Section

2

FIGURE 6. Definition of BioMEMS1

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the primary substrate and structure material. The term bioMEMS first appeared in the early 1990s as MEMS was applied in medicine and bioinstrumentation.

BioMEMS can be divided in two main categories: (1) in vitro bioMEMS, and (2) in vivo bioMEMS. In vitro bioMEMS deals primarily with samples from the body. For example, blood, tissue, serum, urine, and saliva are among the most common body fluids studied. In vivo bioMEMS deals with the living host anatomy. Applications include long term medical implants, surgical tools, artificial organs, and drug delivery13.

Note

For a more detailed explanation of bioMEMS, please refer to “Technology Report”.

Innovation Success FactorsThe emergence of BioMEMS technologies allows smaller, more convenient and user-friendly drug administration and delivery systems. BioMEMS devices are capable of interfacing with single cells using integrated electrical, optical, mechanical and chemical functionality. The following is a list of our device’s primary design innovation factors that improve on the most current designs as shown in Figure 7 (please see “Technology Report” for detailed description of mechanism):

Dual-chambers to allow multiple, independent experiments on a single chip

Circular wells to allow user-friendly cell insertion and perfusion Channel diameter is ~100 micrometers to allow multiple cell

perfusion Disposable and low per-unit cost Clark oxygen sensor to measure cell metabolism*

FIGURE 7. Our device’s final design

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Note

At the time this business strategy report was written, the Clark oxygen sensor was still scheduled to be completed. Due to time constraints, its implementation was removed from our project deliverables.

Product Life Our device is disposable, thus the product life is equal to the length of a given experiment. At the end of the experiment, our device may be disposed using appropriate safety measures.

Key Manufacturing Challenges“80 percent of development [of MEMS devices] time is in manufacturing”

– Martin Schmidt, MIT’s Microsystems Technology Laboratories

The biggest challenge faced by companies seeking to develop BioMEMS devices is that BioMEMS lacks a technological standard, which would stabilize the development of new products. Because manufacturing of BioMEMS devices differ from current manufacturing methods, the emerging BioMEMS market will require a variety of new materials, physical structures, input and output methods, and lower volumes per product. The new manufacturing platform merges conventional and emerging fabrication methods, allowing the greatest number of manufacturing options. By implementing this new manufacturing platform, a number of potential challenges arise, which can cause problems for many BioMEMS companies. Key developmental challenges faced by these companies include1:

Assembly of metal and polymer Materials properties (surface chemistry) Air bubbles in channels Mixing in fluids (laminar flow) Viability of cells within device Low price requirements for disposal Scaling up production from prototypes

Complementary TechnologiesMicroarraysDNA and protein microarrays are a complementary technology to our device because they target gene expression whereas our device will ideally track cell metabolism. They are one of the most popular and important type of LOC device today. They allow highly specific

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analysis of a large number of proteins expressed in various cell types based on particular perturbations. This promotes high throughput screening, thus decreasing the time required for protein separation and characterization. Microarrays involve one of two different types of fabrication methods3:

1. Spotted microarrays, which involves the deposition of pre-existing (ex situ) prepared material, and

2. In situ fabrication, this involves the fabrication of the molecules onto the substrate.

Microfluidic PCRCephoid’s GeneXpert system utilizes the PCR reaction to amplify and detect DNA. This systems allows fully automated PCR testing by preparing samples, amplifying DNA, and detecting DNA. This technology requires microfluidic cartridges with many different internal configurations to allow individualized assays3.

Substitute TechnologiesLabChipThe LabChip by Caliper Life Sciences is a substitute technology to our device because it has similar applications in the drug delivery market to our device. Currently, this chip is extremely popular with pharmaceutical companies, thus Caliper has been able to achieve large revenues and a 17% LOC market share. This device is our largest competing technology.

LabChips utilize capillary tubes to transfer nano-liter volumes of material from standard micro-plate wells to the channels of a microfluidic chip. Once the sample enters the chip, it follows a series of channels to perform the steps required for mixing, incubation, reaction, separation, and detection. Channel movement is controlled via pressure valves. The channels on the LabChip are currently 10 to 50 micrometers in diameter. Our device utilizes perfusion channels that are just under 100 micrometers in diameter and utilizes only pico-liter volumes, which saves significantly more reagent during experimentation. Thus, our device is theoretically more cost efficient for a drug development company.Lab-on-a-CDThe Lab-on-a-CD (LabCD) is a miniaturized assay developed by Tecan. It utilizes a compact disc platform, which fluids are transported using the centrifugal force of a spinning disc. Capillary action draws fluid into a distribution channel, filling a volume definition chamber. As the CD spins, fluid is emptied, leaving a precisely defined quantity of fluid. The microfluidic disc, which contains microfluidic paths, reaction chambers, and valves, is the key component of the LabCD. Less than 10 nanoliters of reagent is required for the drug discovery assay. 3

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High Performance Liquid Chromotography (HPLC) ChipHPLC chips were developed by Agilent for use with their 2100 bioanalyzer system. Currently, the system requires the usage of Caliper’s LabChips. This chip has similar features as the LabChip. 3

Future TechnologiesThe future of our device’s design will be in bio-sensing. There are a multitude of nano-sensors that can be placed on a single chip to allow complete experimental versatility in the laboratory. We believe that many devices will move towards a dual-chamber design in order to increase experimental efficiency. Our circular cell-loading wells figure to also be popular as they are very user-friendly. Figure 8 illustrates a possible future design, which includes the following sensors:

Glucose pH CO2

Lactose

In terms of the entire bioMEMS field, the future lies in the ability to increase the density of testing by first developing a set of bioMEMS technological standards. Nano-arrays are being touted as the next evolutionary step because the nanometer scale resolution offers many advantages in the field of proteomics. Biochip technology is also being utilized to develop a collection of assays. Furthermore, LOC technology is also going to benefit from applications developed from other industries. For example, the technique called flame hydrolysis deposition has many applications in the telecommunications industry. It is now being developed towards the development of new biochips. 3

Safety, Health, and RisksPlease refer to the DesignSafe analysis in the “Technology Report” appendix for more information.

FIGURE 8. Possible future additions to our design

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Corporate Environment

Key CompaniesThe current corporate environment consists primarily of start-ups, a few of which have managed to go public. Figure 7 illustrates that the top five companies account for approximately 48% of the total LOC market in 2004. These companies include Caliper, Cephoid, Agilent, Combimatrix, and Nanogen. The current market is dominated by Caliper, yet this only accounts for roughly 17% of the entire market. Thus, the market for our cell culture device is relatively young and fragmented.

Compared to two years ago, a significantly larger number of products are available today. The market is still emerging, and numerous companies are in the final stages of beta testing. The number of product introductions in 2006 should rise dramatically as compared with 2005. Over the past 5 years, many pharmaceutical and drug discovery companies have installed microfluidic/LOC systems for the purposes of drug discovery3. Among these companies are Pfizer, Eli Lilly, Amgen, Aventis, GlaxoSmithKline, and Proctor and Gamble,

Section

3

FIGURE 7. Microfluidics/LOC competitive market share, 20043

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among others. Table 3 summarizes the current products being developed by the LOC market leaders. 3

Company LOC Device Name(s) Market Share

Public/Private

Caliper Life Sciences

LabChip product line 17% Public

Cepheid SmartCycler; GeneXpert 10% PrivateAgilent

TechnologiesHPLC Chip; 2100 Bioanalyzer;

5100 Automated LOC9% Public

CombiMatrix Corp.

CustomArray 7% Public

Nanogen, Inc. NanoChip product line 5% Public

TABLE 3. Summary of current products developed by LOC market leaders

Caliper Life SciencesCaliper was founded in 1995, utilizing technology developed by Michael Ramsey, a pioneer of microfluidics. Caliper was the first company to market a LOC device, and it is undeniably the LOC market leader, holding a market share of 17%. Caliper currently trades on the NASDAQ stock exchange. 3

Caliper’s line of LOC products works under the name “LabChip”. It is currently partnered with Agilent Technologies, developing LabChips that run in parallel with the 2100 Bioanalyzer. Caliper has the broadest portfolio of LOC devices on the market today. Major pharmaceutical and biotech companies including GlaxoSmithKline, Pfizer, Amgen, Aventis, Millennium, Johnson & Johnson, Amphora and Eli Lilly currently utilize Caliper’s products. 3

CephoidCephoid is a privately-owned company that focuses on systems for rapid diagnosis, pathogen detection, and other PCR-related applications. The company currently sells the SmartCycler system and the GeneXpert system. In 2003, the majority of Cepheid’s sales were generated in the life sciences market, with more than 1400 SmartCycler systems installed in hospitals, university laboratories and pharmaceutical industries. It currently holds a 10% market share in the LOC market. 3

Agilent TechnologiesAgilent Technologies is a spin-off company from the Hewlett-Packard Company. It broke records in November 1999 as the largest public offering (IPO) in Silicon Valley history, raising approximately $2.1 billion from that IPO alone. Agilent is one of the global leaders in LOC devices, claiming a 9% market share despite stiff competition from Caliper and Cephoid. Agilent currently trades on the New York Stock Exchange (NYSE). 3

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Agilent’s main LOC product is the 2100 Bioanalyzer, which is used for the analysis of DNA, RNA, proteins, and cells. Their technology uses a network of channels and wells, which are engraved onto glass or polymer chips to build mini-laboratories. Currently, this technology requires the use of Caliper’s LabChip, but Agilent has taken steps to develop their own chip (HPLC chip). More recently, Agilent launched the 5100 Automated LOC, which allows unattended, high-throughput sizing and quantification of DNA and proteins. 3 CombimatrixCombiMatrix Corp’s primary microfluidic technology products are semi-conductor-based LOC tools for use in identifying the roles of genes, gene mutations and proteins. The four major applications for their CustomArray product line include genetic analysis, nanotechnology, biowarfare defense, and siRNA drug discovery. Its CustomArray product is a DNA microarray. The company is currently trading on the NASDAQ market, and holds major partnerships with Roche, Toppan, Furuno, and Intel.

NanogenNanogen’s primary products are the NanoChip Molecular Biology Workstation and the NanoChip Cartridge. These products integrate microelectronics and molecular biology to detect and identify molecules. The company believes its products provide a key advantage over conventional platforms because they provide “an accurate, simple, versatile and cost-effective integrated microelectronic system that is capable of improving the quality of molecular diagnostic testing while reducing the overall cost.”

Nanogen currently trades on the NASDAQ stock exchange. Since its inception, Nanogen has incurred cumulative net losses, which as of December 2003, stood at approximately $176.3m. To develop and sell their products successfully, the company needs to increase spending levels in R&D as well as in selling, marketing and distribution.

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Economic & Policy Environment

“The regulatory barrier is a huge challenge for [bioMEMS companies]. A lot of the people who have the expertise to manufacture [bioMEMS] have no experience in the rigorous regulatory process. Every iota of the manufacturing process is monitored by the government. It affects the lead time of your products.” 2

- Joseph Baron, a venture capitalist from PureTech Development

“The good news is that the device environment is easier than the drug environment.” 2

- Christoph Westphal, a venture capitalist from Polaris Venture Partners

Government PolicyThough most medical device companies face problems developing the technology, none is more significant than government regulation for medical devices. The United States Food and Drug Administration (FDA) is the primary government entity that regulates our device. The Food and Drug Administration is responsible for protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation. The FDA’s Center for Devices and Radiological Health (CDRH) is the division that is responsible for regulating firms who manufacture medical devices. 14

The class which a medical device is assigned to depends on the type of pre-marketing submission that is required for FDA clearance to the market, the intended use of the device, and the risk the device poses to the patient and/or the user. In order to determine the classification of our device, it is necessary to search for a regulation number by examining the device panels for the medical specialty to which our device would belong.

Section

4

25


Our cell culture device is a Class I device based on the research of similar devices on the market today. Our device is not life-sustaining, and, currently, bioMEMS has no technological standard to adhere to. Thus, a potential device failure poses no risk to life. Based on our

research of similar devices regulated by the FDA, our device is exempt from pre-market notification (510(k)) and good manufacturing practices (GMP), with the exception of general requirements concerning records and complaint files. The selection below is the FDA code of regulation for our device, based on the device listing for a nano-chip developed by Nanogen, Inc. 15:

FDA Regulation 862.2050

TITLE 21—FOOD AND DRUGSCHAPTER I—FOOD AND DRUG ADMINISTRATION

DEPARTMENT OF HEALTH AND HUMAN SERVICESSUBCHAPTER H—MEDICAL DEVICES

PART 862—CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES

Subpart C—Clinical Laboratory Instruments

Sec. 862.2050 General purpose laboratory equipment labeled or promoted for a specific medical use.

(a) Identification. General purpose laboratory equipment labeled or promoted for a specific medical use is a device that is intended to prepare or examine specimens from the human body and that is labeled or promoted for a specific medical use.

(b) Classification. Class I (general controls). The device is identified in paragraph (a) of this section and is exempt from the pre-market notification procedures in subpart E of part 807 of this chapter subject to the limitations in 862.9. The device is also exempt from the current good manufacturing practice regulations in part 820 of this chapter, with the exception of 820.180, with respect to general requirements concerning records, and 820.198, with respect to complaint files.

Patent SearchObviously whenever you are working on a novel design or process one of the most important requirements is to perform a patent search.

Our cell culture device is a Class I device regulated by the FDA. It is exempt from 510(k) pre-market notification and good manufacturing practices (GMP).

26


Fortunately, after doing so there weren’t any existing patents that use the type of design we are working on. Caliper Life Sciences in particular had three or four different patents of microfluidic channel designs that are located below. Again, the designs are different but the overall functionality and use for the designs are all pretty similar.

Patent 1: Microfluidic Controller and Detector System with Self-Calibration SystemUS 6,986,837 B2 Microfluidic controller and detector system with self-calibration Calvin Y. H. Chow, Portola Valley, Calif. (US); Morten J. Jensen, San Francisco, Calif. (US); Colin B. Kennedy, Mill Valley, Calif. (US); Michael M. Lacy, Ben Lomond, Calif. (US); and Robert E. Nagle, Mountain View, Calif. (US) Assigned to Caliper Life Sciences, Inc., Mountain View, Calif. (US) Filed on Aug. 09, 2002, as Appl. No. 10/215,885. Application 10/215885 is a division of application No. 09/374878, filed on Aug. 13, 1999, granted, now 6,498,497. Claims priority of provisional application 60/104260, filed on Oct. 14, 1998. Prior Publication US 2003/0011382 A1, Jan. 16, 2003 Int. Cl. G01N 27/453 (2006.01)

Figure 8 displays a microfluidic controller and detector system, comprising:

a fluidic chip including at least two intersecting channels and a detection zone;

a material direction system comprising an interface configured for contact with the at least two intersecting channels;

an optics block comprising an objective lens disposed adjacent the detection zone, and a light source operable to direct light toward the detection zone via the objective lens;

FIGURE 8. Microfluidic Controller and Detector System with Self-Calibration System

27


a mounting apparatus for focusing light from the light source onto the detection zone via the objective lens, the mounting apparatus comprising a first and a second adjacent plates, a pivot, and an actuator for displacing the first plate relative to the second plate about the pivot; and

A control system coupled to the optics block and adapted to receive and analyze data from the optics block.

Patent 2: Multi-Reservoir Pressure Control SystemUS 6,915,679 B2 Multi-reservoir pressure control system Ring-Ling Chien, San Jose, Calif. (US); J. Wallace Parce, Palo Alto, Calif. (US); Andrea W. Chow, Los Altos, Calif. (US); and Anne Kopf-Sill, Portola Valley, Calif. (US) Assigned to Caliper Life Sciences, Inc., Mountain View, Calif. (US) Filed on Feb. 23, 2001, as Appl. No. 9/792,435. Claims priority of provisional application 60/216793, filed on Jul. 07, 2000. Claims priority of provisional application 60/184390, filed on Feb. 23, 2000. Prior Publication US 2001/0052460 A1, Dec. 20, 2001 This patent is subject to a terminal disclaimer. Int. Cl.7G01N 11/00

Figure 9 displays a microfluidic system comprising: a body defining a

microfluidic channel network and a plurality of reservoirs in fluid communication with the network, the network including a channel;

a plurality of pressure modulators, each pressure modulator providing a selectably variable pressure; and

A plurality of pressure transmission lumens, the lumens transmitting the pressures from the pressure modulators to the reservoirs so as to induce a desired flow within the channel.

Patent 3: Cell Flow Apparatus and Methods for Real-Time Measurements of Patient Cellular Response

US 6,958,221 B2 Cell flow apparatus and method for real-time measurements of patient cellular responses Pandi Veerapandian, San Diego, Calif. (US); and

FIGURE 9. Multi-Pressure Reservoir System Design

28


Gregory Kaler, San Diego, Calif. (US) Assigned to Caliper Life Sciences, Inc., Mountain View, Calif. (US) Filed on Dec. 23, 2002, as Appl. No. 10/328,670. Application 10/328670 is a continuation of application No. 09/779690, filed on Feb. 07, 2001, granted, now 6558916. Application 09/779690 is a continuation in part of application No. 09/568778, filed on May 10, 2000, granted, now 6242209, filed on Jun. 05, 2001. Application 09/568778 is a continuation of application No. 09/370786, filed on Aug. 05, 1999, granted, now 6280967, filed on Aug. 28, 2001. Application 09/370786 is a continuation in part of application No. 09/317793, filed on May 24, 1999, granted, now 6096509, filed on Jul. 06, 1999. Application 09/317793 is a continuation of application No. 08/904904, filed on Aug. 01, 1997, granted, now 5919646, filed on Jul. 06, 1999. Application 08/904904 is a continuation in part of application No. 08/691356, filed on Aug. 02, 1996, granted, now 5804436, filed on Sep. 08, 1998. Prior Publication US 2003/0129669 A1, Jul. 10, 2003 Int. Cl.7C12Q 1/02

This automated method for determining the effect of each of a plurality of test agents on cells from a subject comprising:

obtaining cells from said subject; sequentially combining each of a plurality of samples

comprising said cells with one or more of said test agents to form each of a plurality of test mixtures in a computer controlled apparatus; and

Sequentially directing each of said plurality of test mixtures through a detection zone in said apparatus, said detection zone being capable of detecting the effect of said agents on said cells.

Patent 4: Apparatus for Continuous Liquid Flow in Micro-scale Channels Using WickingUS 6,989,128 B2 Apparatus for continuous liquid flow in microscale channels using wicking Marja Liisa Alajoki, Palo Alto, Calif. (US); H. Garrett Wada, Atherton, Calif. (US); and Robert S. Dubrow, San Carlos, Calif. (US) Assigned to Caliper Life Sciences, Inc., Mountain View, Calif. (US) Filed on May 08, 2002, as Appl. No. 10/142,263. Application 10/142263 is a continuation of application No. 09/245627, filed on Feb. 05, 1999, granted, now 6,416,642. Claims priority of provisional application 60/116602, filed on Jan. 21, 1999. Prior Publication US 2002/0179445 A1, Dec. 05, 2002 This patent is subject to a terminal disclaimer. Int. Cl. B01L 3/02 (2006.01); G01N 27/453 (2006.01)

Figure 10 shows the microfluidic device comprising:

29


a body structure having at least two intersecting microchannels fabricated therein;

a reservoir fluidly coupled to the at least two intersecting microchannels and having an aperture allowing external access to the body structure; and,

A wick positioned within the reservoir in fluidic communication with the at least two intersecting microchannels, which wick is configured to modulate fluid flow in the at least two intersecting microchannels during operation of the device.

Technology Intelligence“BioMEMS is imperative for new methods of drug delivery like the inhaler made by Boeringer-Ingelheim (with Steag Microparts) and the MEMS array made by MicroCHIPS.”

- Ellen McDevitt, MEMS Industry Group

Industry Contact LogName Position Company/

OrganizationPhone/E-mail Conta

ct Date

Farrell, Doug

Investor Relations

Affymetrix, Inc. [email protected]

Tel: 888-362-2447

2/1406

Foran, Margaret

Secretary of

Corporate Governanc

e

Pfeizer, Inc. [email protected]@pfizer.com

[email protected]

2/12/06

Grace, Roger

Author Roger Grace Associates [email protected]

Tel: 415-436-9101

2/14/06

Henrikson, Tracy

Employee Orchid Cellmark [email protected] 2/15/06

FIGURE 10. Apparatus for Continuous Liquid Flow in Micro-scale Channels Using Wicking

Section

5

30








McDevitt, Ellen

Executive Director

MEMS Industry Group [email protected]

Tel: 412-390-1644

2/8/06

Tamir, Ronen

Head of Investor Relations

Novartis [email protected]

Tel: 212-830-2433

2/12/06

N/A Company website

Integrated Sensing Systems (ISSYS)

www.mems-issys.com

Tel: 734-547-9896

2/12/06

N/A Company website

Microchips, Inc. www.mchips.com

Tel: 781-275-1445

2/12/06

N/A Company website

Johnson & Johnson www.jnj.com/contact_us 2/12/06

N/A Company website

Caliper Life Sciences Tel: 508-435-9500 2/14/06

N/A Company website

Cepheid Tel: 408-541-4191 2/14/06

The table above represents every person, company, or organization that the business team attempted to contact. Not everyone responded to our inquiries. The information received from these contacts has been included throughout this report. Ellen McDevitt of the MEMS Industry Group proved to be the most helpful contact. She informed us of the companies currently developing BioMEMS devices. We found that the large companies chose to not comment on the BioMEMS market. For example, the following is a response from Pfeizer:

Dear Mr. Dempsey,

Your e-mail sent to Pfizer's Corporate Governance Committee Chair hasbeen forwarded to us for reply. Thank you for taking the time to writeto us and for your interest in our Company's perspective on the emergingBioMems industry.

However, please note that evaluating the BioMems industry and sharingour Company's perspective on that industry, is not a function of ourBoard of Directors.

All public information regarding our Company and its views on ourbusiness and industry outlook can be found in several SEC filingsavailable on our website. Please view the most recent Financial Reportand Form 10-K and as well as other publicly available information.

Again, thank you for your interest in Pfizer and for taking the time to

31

http://www.jnj.com/contact_us

http://www.mchips.com/

http://www.mems-issys.com/






write to us.

Sincerely,

Pfizer Corporate Governance

Project Valuation & FinancingFinancial AnalysisThe purpose of the following financial analysis is to evaluate the investment decision associated with our device in the eyes of a venture capitalist. We are going to assess our projected cash flows for our device and make a decision to accept or reject the project based on its net present value (NPV). NPV is the value of the device’s future cash flows, discounted at the appropriate cost of capital.

Methods & AssumptionsThe following is a list of assumptions made in order to develop our model (the numbers were chosen subjectively by the business team):

1. Our group has formed a start-up company, whose primary marketable technology is our bioMEMS device

2. Project began design in 2001 (to include past senior design projects)

3. NPV > 0 indicates the project should be accepted4. NPV < 0 indicates the project should be rejected5. Discount rate = 10%6. Initial share of served market = 1%7. Initial manufacturing unit cost (includes labor) = $5.008. Sales price = $5.009. Total annual market (units) based on Figure 310. Operating expenses = 60% of cost of goods sold11. Design (R&D) costs = $500,000 per year12. Capital investment = $1,000,000.0013. Experience curve factor = 20%

Section

6

32


Pro Forma Profit and Loss StatementSee next page.

Project RecommendationThe NPV of our project is $6,612,618 for the period between 2001 and 2010. Therefore, we should accept the project because it is profitable.

33


Pro Forma Profit and Loss StatementMEMS in the Market - Pro Forma Profit and Loss Statement

Color coding: Data entry cells. Modify to reflect your project.

Extrapolation from Green cell to left. Modify as necessary to reflect outyear projection.Instructions Formula: Don't modify unless you need to revise worksheet structure.

Modify cells in Green; other cells are formulas.

You may also modify outyear cells in yellow to adjust for year-to-year changes.

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 Total

Total Annual Market (units) 43060000 53880000 67920000 92260000 124660000 164280000 214700000 249900000

1,010,660,000

Served Market (% of total) 70% 70% 70% 70% 70% 70% 70% 70%

Served Market (units) 301420003771600

04754400

06458200

0 8726200011499600

015029000

017493000

0 707,462,000

Share of Served Market (%) 1% 1% 2% 2% 3% 3% 4% 5%

New Unit Sales 301,420 377,160 950,8801,291,64

0 2,617,860 3,449,880 6,011,600 8,746,500 Aftermarket Sales 0 0 83 109 713,160 968,730 1,963,395 2,587,410 6,232,887

Total Unit Sales 301,420 377,160 950,9631,291,74

9 3,331,020 4,418,610 7,974,99511,333,91

0 29,979,827 Sales Price $5 $5 $4 $4 $4 $3 $3 $3

======

=========

=======

=======

========

========

=========

========

========

========

==

Design Costs$500,000.

00

Capital Investment 1,000,000.

00

Sales Revenue $1,507,10

0 $1,753,7

94 $4,112,4

39 $5,195,1

37 $12,458,8

81 $15,369,8

78 $27,740,5

56 $39,424,3

47 $107,562,13

2 Unit Production Cost $5.00 $3.87 $2.94 $2.42 $1.90 $1.57 $1.30 $1.09

Cost of Goods Sold $1,507,10

0 $1,461,2

54 $2,799,6

08 $3,121,1

29 $6,325,85

5 $6,959,11

8 $10,365,5

41 $12,362,7

36

Gross Margin $0 $292,540 $1,312,8

31 $2,074,0

08 $6,133,02

6 $8,410,76

0 $17,375,0

15 $27,061,6

11

Operating Expense $904,260 $876,752 $1,679,7

65 $1,872,6

77 $3,795,51

3 $4,175,47

1 $6,219,32

5 $7,417,64

2

Net Before Tax ($500,000) $0 ($904,260

)($584,21

3)($366,93

3) $201,330 $2,337,51

3 $4,235,28

9 $11,155,6

90 $19,643,9

69 Depreciation $200,000 $200,000 $200,000 $200,000 $200,000

Tax ($230,000) ($92,000)($507,960

)($360,73

8)($260,78

9) $612 $1,075,25

6 $1,948,23

3 $5,131,61

7 $9,036,22

6

Taxes Owed $0 $0 $0 $0 $0 $0 $0 $1,572,61

4 $5,131,61

7 $9,036,22

6

Net After Tax ($500,000) $0 ($904,260

)($584,21

3)($366,93

3) $201,330 $2,337,51

3 $2,662,67

5 $6,024,07

3 $10,607,7

43 ====== ======= ====== ===== ===== ===== ====== ====== ====== ======

34


== = == === === === == == == ==

Net Cash Flow ($500,000)($1,000,00

0)($904,260

)($584,21

3)($366,93

3) $201,330 $2,337,51

3 $2,662,67

5 $6,024,07

3 $10,607,7

43 Discount Rate 10%

NPV$6,612,6

18 Experience Curve Effects on your initial unit cost* *Assumes experience curve effects don't take effect until 100 units have been built. Experience Curve Factor 20% Yr: 1 2 3 4 5 6 7 8 9 10 Volume 301,420 377,160 950,963 1,291,749 3,331,020 4,418,610 7,974,995 11,333,910

Cumulative Volume (CV) 301,420 678,580 1,629,54

3 2,921,29

2 6,252,312 10,670,92

2 18,645,91

7 29,979,82

7 % Change in CV 225% 240% 179% 214% 171% 175% 161% Variable Cost/Unit $5.00 $3.87 $2.94 $2.42 $1.90 $1.57 $1.30 $1.09

35


New, Aftermarket, and Total Unit Sales

0

2,000,000

4,000,000

6,000,000

8,000,000

10,000,000

12,000,000

2001 2002 2003 2004 2005 2006 2007 2008

Year

Ann

ual S

ales

(uni

ts)

New Unit SalesAftermarket SalesTotal Unit Sales

36


Annual Net Cash Flow

($2,000,000)

$0

$2,000,000

$4,000,000

$6,000,000

$8,000,000

$10,000,000

$12,000,000

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Year

Net

Cas

h Fl

ow

37


Literature 1. Bouchaud, Jeremie. “BioMEMS: high potential but also highly

challenging.” Wicht Technology Consulting, Munich. 21 February 2006.

2. Clark, Lauren. “BioMEMS: Mini Medical Devices with Major Market Potential.” MIT Deshpande Center Ignition Forum. 8 December 2003. http://web.mit.edu/deshpandecenter

3. Patel, Nelesh. “Emerging Drug Discovery Technologies.” Business Insights: Healthcare. April 2005.

4. Allan, Roger. “BioMEMS Making Huge Inroads Into Medical Market.” Electronic Design. 16 June 2003. http://www.elecdesign.com/Articles/Index.cfm?AD=1&AD=1&ArticleID=5050

5. Brown, Chappell. “Chip Makers Looking at BioMEMS.” EE Times Online. 27 March 2003. http://www.eet.com/story/OEG20030327S0019

6. “Drug Manufacturers and Drug Delivery Industries.” Yahoo! Finance Industry Center. 27 March 2006. http://biz.yahoo.com/ic/index.html

7. Selvakumar, Arjun, Yuh-Min Chang, Simon Sims, Jamie Wibbenmeyer. “BioMEMS for Future Drug Discovery Needs.” Applied MEMS, Inc. 2004. www.appliedmems.com

8. Cabuz, Cleopatra. “The Potential of MEMS.” Design News. 24 October 2005, Volume 60 Issue 15, p22.

9. DiMasi, Joseph, Ronald Hansen, Henry G. Grabowski. “The price of innovation: new estimates of drug development costs.” Journal of Health Economics. March 2003, Vol. 22 Issue 2, p151.

10. Jarvis, Lisa. “Drug Development Costs Soar to Record High Levels.” Chemical Market Reporter. 24 June 2002. Volume 261 Issue 25, p10.

Section

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38

http://www.appliedmems.com/

http://biz.yahoo.com/ic/index.html

http://www.eet.com/story/OEG20030327S0019

http://www.elecdesign.com/Articles/Index.cfm?AD=1&AD=1&ArticleID=5050

http://www.elecdesign.com/Articles/Index.cfm?AD=1&AD=1&ArticleID=5050

http://web.mit.edu/deshpandecenter


11. Gerde, Virginia, Raj V. Mahto, “Disruptive technology and interdependence: The relationships of BioMEMS technology and pharmaceutical firms.” The Journal of High Technology Management Research, Volume 15, Issue 1, February 2004, Pages 73-89.

12. Pick, Neora, Scott Cameron, Dorit Arad, Yossef Av-Gay. “Screening of compounds toxicity against human monocytic cell line-THP-1 by flow cytometry.” Biological Procedures Online. 2004, Vol. 4, pgs. 220-225.

13. Lee, Abraham P. “BioMEMS: Bridging Nano and Micro to Link Diagnostics to Treatment.” Department of Biomedical Engineering. University of California at Irvine.

14. King, Paul H., Richard C. Fries. “The Food and Drug Administration.” Design of Biomedical Devices and Systems. New York: Marcel Dekker, 2003.

15. “Nanochip Reader.” Center for Devices and Radiological Health: Device Listing Database. United States Food and Drug Administration. 9 April 2006. www.fda.gov

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http://www.fda.gov/

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