A EXPLORATORY STUDY OF DEVICING A BIOCHIP IN HUMAN BEING AS A DIAGNOSTIC TOOL BY S. NIRMALA

ROLL NO 0906MBA0962REG.NO 68209200030

A PROJECT REPORT Submitted to the `FACULTY OF MANAGEMENT SCIENCES

In partial fulfillment for the award of the degree Of

MASTER OF BUSINESS ADMINISTRATION

CENTRE FOR DISTANCE EDUCATION ANNA UNIVERSITY CHENNAI 600 025 AUGUST, 2011

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Certified that the Project report titled A EXPLORATORY STUDY OF DEVICING A BIOCHIP AS A DIAGNOSTIC TOOL is the bonafide work of Mrs. S.NIRMALA who carried out the work under my supervision. Certified further that to the best of my knowledge the work reported herein does not form part of any other project report or dissertation on the basis of which a degree or award was conferred on an earlier occasion on this or any other candidate.

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Name: S. NIRMALA Name: SURESH SRINIVASANRoll No. : 0906MBA0962Designation:Reg. No. : 68209200030Address:

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This is to certify that Thiru/Ms. /Tmt. S.NIRMALA...(Roll No .68209200030 ; Register No 0906MBA0962) has been subjected to Viva-voce-Examination on 11.09.2011 (Date) at ..(Time) at theStudy centre A.C.TECH.... (Name and Address of the Study centre).

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ABSTRACTWorld today faces serious health issues which are not screened on the onset and leads to end stage diseases like Diabetes mellitus, Coronary heart disease, Respiratory disease and many more. Out of which Diabetes is pandemic, which is prevalent in both developed and developing countries. In the year 2000, various studies estimated around 175 million people with diabetes worldwide and by 2030, the projected estimate of diabetes is 354 million. The solution to diabetics is more frequent testing, using a less invasive method. Various companies are trying new technologies like extracting the required body fluid, using either an electric current or a tiny pore induced by a laser or a small needle. One of the key parameter to diagnose diabetic is only by early screening and therapeutic interventions. The advanced technology like biochip can be utilized for preventing from end stage disease of diabetics without any current process like body fluid extraction. Possibility of using biochip for early detection of diabetes in human being could happen in medical evolution.

ACKNOWLEDGEMENT

I wish to express my deep sense of gratitude and indebtness to Suresh Srinivasan, Professor, Management of studies, Centre for Distance Education, Anna University for suggesting this problem, for his impeccable guidance, his continued and sustained help throughout the course of this investigationI am grateful to Prof Director, for providing the necessary infrastructures.I wish to place on record my wholehearted gratitude to Mr.S.Shanmugam, for his constant inspiration and encouragement to build up this work This successful of this study would not have been possible without the support of my family. I sincerely thank them for the belief and confidence they had in me.

TABLE OF CONTENTSCHAPTERSTITLEPAGE NO:1. INTRODUCTION1.1 RESEARCH BACKGROUND1.2 PROBLEM DEFINITION1.3 NEED FOR THE STUDY1.4 OBJECTIVES AND SCOPE1.5 DELIVERABLES 2. LITERATURE SURVEY

2.1 REVIEW OF LITERATURE 2.2 RESEARCH GAP3. METHODOLOGY 3.1 TYPE OF PROJECT 3.2 TARGET RESPONDENT 3.3 ASSUMPTIONS AND LIMITATION 3.4 SAMPLING METHODS 3.5 DATA PROCESSING 3.6 ANALYSIS TOOL 4. DATA ANALYSIS AND INTERPRETATION 4.1 PERCENTAGE ANALYSIS 4.2 Weighted average method 4.2 CHI-SQUARE TEST 4.3 REGRESSION ANALYSIS 4.4 ANNOVA TABLE

5 CONCLUSIONS 5.1 SUMMARY AND FINDINGS 5.2 Suggestions & Recommendations

5.3 Conclusions

5.4 Directions for Future Research

Appendix

Copy of Questionnaire/Interview Schedule

Any Other related documentsReferences

List of Tabless.notable namepage no 1Respondents age group 2Type of respondents 3Percentage of diabetes 4Percentage of non-diabetes for checkup 5 Frequency of checkup 6Symptoms provoked for Checkup 7Diagnosis of Diabetes 8Other ailments other than diabetes 9Usage of Personal Instrument 10Acceptance of New device 11Reliability on New device 12Preference in future 13Affordable 14Level of Satisfaction about availability 15 Level of Satisfaction about the Device

CHAPTER 1INTRODUCTION1.1 RESEARCH BACKGROUNDDiabetes Mellitus is a common metabolic disorder resulting from defects in insulin action, insulin production, or both. Insulin, a hormone secreted by the pancreas, helps the body use and storage produced during the digestion of the food. Characterized by hyperglycemia, symptoms of diabetes include frequent urination, increased thirst, dehydration, weight loss, blurred vision, fatigue, and occasionally, coma. Uncontrolled hyperglycemia over time damages the eyes, nerves, blood vessels, kidneys, and heart, causing organ dysfunction and failure. A number of risk factors are attributed to the incidence of diabetes, including family history, age, ethnicity, and social group characteristics, as well as behavioral, lifestyle, psychological, and clinical factors.According to the World Health Organisation estimates, India had 32 million diabetic subjects in the year 2000 and this number would increase to 80 million by the year 2030. The International Diabetes Federation (IDF) also reported that the total number of diabetic subjects in India is 41 million in 2006 and that this would rise to 70 million by the year 2025. So far, the screening method for diabetes is only through body fluid extract. This method is used mostly after the onset of disease and self screening is not possible. In such scenario there is a need for easy and convenient way to early screening as much as possible to avoid uncertainty of human life. Biochip- The most exciting future technology as a outcome of the fields Computer science, Electronics and Biology. Biochips are the basis for miniaturized biochemical assays, and offer many advantages over the conventional analytical methods.The most significant of which are: i) a variety of analysts can be investigated simultaneously in the same sample,ii) the required sample quantities are minimal,iii) low consumption of scarce reagents, iv) high miniaturization andv) high sample throughput. Biochip was originally developed in 1983 for monitoring fisheries, the rapid technological advances of the biochemistry and semiconductor fields in the 1980s led to the large scale development of biochips in the 1990s. At this time, it became clear that biochips were largely a "platform" technology which consisted of several separate, yet integrated components. Today, a large variety of biochip technologies are either in development or being commercialized. Biochips are also continuing to evolve as a collection of assays that provide a technology platform. One interesting development in this regard is the recent effort to couple so-called representational difference analysis (RDA) with high-throughput DNA array analysis. A single probe contains identical molecules, for this reason it is also called feature. 1.2 PROBLEM IDENTIFIEDAs diabetic becomes a major health challenge worldwide, we need to execute the early screening and therapeutic interventions towards achieving preliminary prevention of its complication. Devising product like biochip may be an apt solution for such scenario to assist in treating diabetic patients from critical phase.1.3 NEED FOR THE STUDYSince diabetes is a serious health challenge if not screened on the onset may lead to end stage diseases of Diabetes mellitus, Coronary heart disease, Respiratory disease and many more. Out of which Diabetes is pandemic, which is prevalent in both developed and developing countries. In the year 2000, various studies estimated around 175 million people with diabetes worldwide and by 2030, the projected estimate of diabetes is 354 million. The solution is more frequent testing, using a less invasive method. Various companies are trying to extract the required body fluid, using either an electric current or a tiny pore induced by a laser or a small needle. One of the key parameter to diagnose diabetic is only by early screening and therapeutic interventions. The advanced technology like biochip can be utilized for preventing from end stage disease of diabetics without any current process like body fluid extraction.This work attempts to study the feasibility of such an innovative product (biochip) which enhances the early detection of the organ malfunction, in such diseases as the onset is hard to detect and prolong exposure mostly lead to end stage organ failures which may intern become almost not viable to treat in a precarious stage of patients. This study basically wants to bring the unique benefits of biochip over the current application which is used as identification of people from population in an area.1.3 OBJECTIVETo explore the possibility of devising biochip in human beings as an organ diagnostic tool for early screening of diabetes1.4 SCOPEThe immediate prospects for biochip technology depend on a range of technologic and economic issues. One is the question of chip reusability. An overarching issue is standardization. An optimum biochip strategy is not yet discernible. Even as efforts at standardization proceed, novel technologic options continue to emerge.1.5 DELIVERABLESA major development problem will be to bring industrial quality at the level of microelectronics: homogeneity, reproducibility, reliability. A unified patent law should be envisioned that allows for an efficient and timesaving procedure for information exchange between universities and industry.Funding agencies should provide patent support, both financially as well as intellectually. The great potential it has may bring a revolution to many fields in life science and medicine in the coming century.

CHAPTER-2LITERATURE SURVEY2.1 Review of literatureDiabetes represents a spectrum of metabolic disorders, which has become a major health challenge worldwide. Diabetes is pandemic in both developed and developing countries. In the year 2000, various studies estimated around 175 million people with diabetes worldwide and by 2030, the projected estimate of diabetes is 354 million. According to World Health Organisation estimates, India had 32 million diabetic subjects in the year 2000 and this number would increase by 80 million by the year 2030.Long standing diabetes mellitus is associated with an increased prevalence of micro- vascular and macro-vascular diseases. The onset of Type 2 diabetes is usually insidious and patient may remain asymptomatic until late stages of the disease. A study by Mohan et al, in south India found it in 34.1% of their patients According to a survey published in 2003, diabetes nephropathy was the most common cause of end stage renal disease in 9 out of 10 Asian countries, with an incidence that an incidence that had increased from 1.2% of the overall population with end-stage renal diseases in renal disease in 1998 to 14.1% in 2000. Early screening and therapeutic interventions are the first steps towards achieving preliminary prevention of diabetes and its complication.The solution is more frequent testing, using a less invasive method. Various companies are trying to extract the required body fluid, using either an electric current or a tiny pore induced by a laser or a small needle. A biochip could play a vital role in detecting or preventing from such a scenario. The biochip technology was originally developed in 1983 for monitoring fisheries, its use now includes, over 300 zoos, over 80 government agencies in atleast 20 countries, pets, electronic branding of horses, monitoring lab animals, fisheries, endangered wild life, automobiles, garment tracking, hazardous waste, and according to the experts-humans. Todays biochip implant is basically a small (micro) computer chip, inserted under the skin, for identification purposes. The biochip implant system consists of two components; a transponder and a reader or scanner. The transponder is the actual biochip implant. The biochip system is radio frequency identification (RFID) system, using low-frequency radio signals to communicate between the biochip and reader. The reading range or activation range, between reader and biochip is small, normally between 2 and 12 inches. This could be used to detect the functions of organ which would definitely save the life from end stage diseases which may be even lethal if they are unknown or not detected. To bring such a product to save many lives as diabetes is emerging disease worldwide.

Fig 1.1 Biochip

Generation/History

The development of biochips has a long history, starting with early work on the underlying sensor technology. Biochip was originally developed in 1983 for monitoring fisheries, the rapid technological advances of the biochemistry and semiconductor fields in the 1980s led to the large scale development of biochips in the 1990s. At this time, it became clear that biochips were largely a "platform" technology which consisted of several separate, yet integrated components. Today, a large variety of biochip technologies are either in development or being commercialized. Numerous advancements continue to be made in sensing research that enable new platforms to be developed for new applications. Biochip was invented in 4G generation & the development is still continued, due its various applications. Biochips are also continuing to evolve as a collection of assays that provide a technology platform. One interesting development in this regard is the recent effort to couple so-called representational difference analysis (RDA) with high-throughput DNA array analysis.Many developments over the past two decades have contributed to its evolution.In a sense, the very concept of a biochip was made possible by the work of Fred Sanger and Walter Gilbert, who were awarded a Nobel Prize in 1980 for their pioneering DNA sequencing approach that is widely used today. DNA sequencing chemistry in combination with electric current, as well as micropore agarose gels, laid the foundation for considering miniaturizing molecular assays. Another Nobel-prize winning discovery, Kary Mullis's polymerase chain reaction (PCR), first described in 1983, continued down this road by allowing researchers to amplify minute amounts of DNA to quantities where it could be detected by standard laboratory methods. A further refinement was provided by Leroy Hood's 1986 method for fluorescence-based DNA sequencing, which facilitated the automation of reading DNA sequence. Further developments, such as sequencing by hybridization, gene marker identification, and expressed sequence tags, provided the critical technological mass to prompt corporate efforts to develop miniaturized and automated versions of DNA sequencing and analysis to increase throughput and decrease costs. In the early and mid-1990s, companies such as Hyseq and Affymetrix were formed to develop DNA array technologies.

Biochip, its Parts and Working The current, in use, biochip implant system is actually a fairly simple device. Biochip implant is basically a small (micro) computer chip, inserted under the skin, for identification purposes. The biochip implant system consists of two components; a transponder and a reader or scanner. The transponder is the actual biochip implant. The biochip system is radio frequency identification (RFID) system, using low-frequency radio signals to communicate between the biochip and reader. The reading range or activation range, between reader and biochip is small, normally between 2 to12 inches.The transponderThe transponder is the actual biochip implant. It is a passive transponder, meaning it contains no battery or energy of it's own. In comparison, an active transponder would provide its own energy source, normally a small battery. Because the passive biochip contains no battery, or nothing to wear out, it has a very long life, up to 99 years, and no maintenance. Being passive, it's inactive until the reader activates it by sending it a low-power electrical charge. The reader "reads" or "scans" the implanted biochip and receives back data (in this case an identification number) from the biochip. The communication between biochip and reader is via low-frequency radio waves. The biochip-transponder consists of four parts; computer, microchip, antenna coil, capacitor and the glass capsule.

Fig 1.2 Components

Computer Microchip:The microchip stores a unique identification number from 10 to 15 digits long. The storage capacity of the current microchips is limited, capable of storing only a single ID number.The unique ID number is "etched" or encoded via a laser onto the surface of the microchip before assembly. Once the number is encoded it is impossible to alter. The microchip also contains the electronic circuitry necessary to transmit the ID number to the "reader". Antenna Coil:This is normally a simple, coil of copper wire around a ferrite or iron core. This tiny primitive radio antenna receives and sends signals from the reader or scanner. Tuning Capacitor:The capacitor stores the small electrical charge (less than 1/1000 of a watt) sent by the reader or scanner, which activates the transponder. This "activation" allows the transponder to send back the ID number encoded in the computer chip. Because "radio waves" are same frequency as the reader.

Glass Capsule:The glass capsule "houses" the microchip, antenna coil and capacitor. It is a smallcapsule, the smallest measuring 11 mm in length and 2 mm in diameter, about the size of an uncooked grain of rice. The capsule is made of biocompatible material such as soda lime glass. After assembly, the capsule is hermetically is very smooth and susceptible to movement, a material such as a polypropylene polymer sheath is attached to one end of the capsule. This sheath provides a compatible surface which the bodily tissue fibers bond or interconnect,resulting in a permanent placement of the biochip.

Biochip and Syringe The biochip is inserted into the subject with a hypodermic syringe. Injection is safe and simple, comparable to common vaccines. Anesthesia is not required nor recommended. In dogs and cats, the biochip is usually injected behind the neck between the shoulder blades.

Fig 1.3 Syringe and Biochip

The reader:The reader consists of an "exciter" coil which creates an electromagnetic field that, via radio signals, provides the necessary energy (less than 1/1000 of a watt) to "excite" or "activate" the implanted biochip. The reader also carries a receiving coil that receives the transmitted code or ID number sent back from the "activated" implanted biochip. This all takes place very fast, in milliseconds. The reader also contains the software and components to decode the received code and display the result in an LCD display. The reader can include a RS-232 port to attach a computer. The reader and biochip can communicate through most materials, except metal

The Reader or Scaner Notice the ID number in the LCD displayFig 1.4 Reader or Scanner

Types of Chips From these beginnings, three general types of biochips have emerged1. plate-based DNA arrays2. gel-based3. DNA arrays, and microfluidic biochips. The plate- and gel-based arrays use essentially the same principles to achieve the same end. On asubstrate such as a glass plate or a porous gel, the manufacturer immobilizes the biochip's probes, a large set of nucleic acid single strands, each carrying a known genetic sequence.Current biochips have tens of thousands of probes, each with a length of 10 to 15 bases. Such an array is sufficient to test an individual gene throughout all or part of its length forsingle-base variations from the gene's usual sequence. In particular, individualGeneChips detect single-base variations in the human genes BRCA1 and BRCA2 (breast-cancer-related), p53(a tumor suppressor gene mutated in many forms of cancer), and P450 (coding for a key liver enzyme system that metabolizes drugs). Other GeneChips analyze the genome of HIV (human immunodeficiency virus) for variations within the code for the viral protease and reverse transcriptase. The intent is to help predict drug resistances of a given patient's viral strain. The probes in DNA-array biochips are required to overlap along the length of the gene being examined. To detect single-base variations, further redundancies are needed. For this purpose, the probes are provided in sets of five, within which the probes are identical to each other except at a single site somewhere along their length, where one probe tests for A, a second for T, a third for G, a fourth for C, and a fifth for no nucleotide (a single-base deletion). In essence, then, a DNA-array biochip does not conduct actual sequencing reactions. Instead, examining a specific gene, it can test simultaneously for myriad variations on the theme of the normal gene. The testing may be facilitated by representational difference analysis, which compares the results for two tissue samples. Subtraction of one set of results from the other shows which genes are active in one sample but less active or completely inactive in the other. The comparison might be between normal and cancer cells, or between metastatic and non metastatic cancers. In this way, the evaluation may pinpoint an abnormal cellular process occurring chiefly or even exclusively in diseased cells. The evaluation may thus serve not only as a diagnostic tool but also as a means to identify therapeutic targets. The HyX Gene Discovery Modules now beingmanufactured by HySeq test simultaneously for expression of 30,000 to 50,000 genes. DNA biochip development of a truly integrated having a phototransistor integrated circuit (IC) microchip has been reported by Vo-Dinh and coworkers. This work involves the integration of a 4 X 4 and 10 X 10 optical biosensor array onto an integrated circuit. Most optical biochip technologies are very large when the excitation source and detector are considered, making them impractical for anything but laboratory usage. In this biochip the sensors, amplifiers, discriminators and logic circuitry are all built onto the chip. In one biochip system, each of the sensing elements is composed of 220 individual phototransistor cells connected in parallel to improve the sensitivity of the instrument. The ability to integrate light emitting diodes (LEDs) as the excitation sources into the system is also discussed. An important element in the development of the multifunctional biochip (MFB) involves the design and development of an IC electro-optic system for the microchip detection elements using the complementary metal oxide silicon (CMOS) technology. With this technology,

Fig.1.4 Schematic diagram of an integrated DNA biochip system highly integrated biochips are made possible partly through the capability of fabricating multiple optical sensing elements and microelectronics on a single system. Applications of the biochip are illustrated by measurements of the HIV1 sequence-specific probes using the DNA biochip device for the detection of a gene segment of the AIDS virus70. Recently, a MFB which allows simultaneous detection of several disease end-points using different bioreceptors, such as DNA, antibodies, enzymes, and cellular probes, on a single biochip system was developed71. The MFB device was a self-contained system based on an integrated circuit including photodiode sensor arrays, electronics, amplifiers, discriminators and logic circuitry. The multi-functional capability of the MFB biochip device is illustrated by measurements of different types of bioreceptors using DNA probes specific to gene fragments of the Mycobacterium Tuberculosis (TB) system, and antibody probes targeted to the cancer related tumor suppressor gene p53.The microfluidic chip is different from a DNA array. Instead of providing nucleic acid probes, it offers channels through which fluids can flow, typically under the impetus of an applied electric field. It also enables the fluids to meet, typically in nanoliter quantities.Two fluids may, for instance, converge along the short arms of a Y-shaped set of channels. Where they meet, a reaction occurs, and the results flow down the stem of the Y, to be sensed at the channel's far end. Alternatively, the outcome fluid may encounter another reagent delivered at a subsequent junction and undergo a further reaction . The chip contains a 10 character alphanumeric identification code that is never duplicated when a scanner is passed over the chip, the scanner emits a 'beep' and your ... number flashes in the scanner's digital display." Biochips concentrate thousands of different genetic tests on a surface area of just a few square centimetres so that they can be analysed by computer within a very short space of time. On the one hand this makes the individual genetic tests much cheaper and on the other hand, thanks to the capacity, many more tests can be carried out.Biochips concentrate thousands of different genetic tests on a surface area of just afew square centimetres so that they can be analysed by computer within a very shortspace of time. On the one hand this makes the individual genetic tests much cheaperand on the other hand, many more tests can be carried out.Affymetrix invented the high-density microarray in 1989 and has been selling thisassay since 1994 under the name of GeneChip (figure 1). In this context,microarray means that the genetic tests are organised (arrayed) inmicrometrespacing(micro). As it was not previously possible to go below the millimetre range,the description high density is certainly justified. Experiments (e.g. measurement ofgene activity or sequencing to demonstrate mutations and polymorphisms) that couldpreviously only be done individually, one after the other, can now be carried out inlarge numbers at the same time and in a highly automated manner.

CostBiochips are not cheap, though the price is falling rapidly. A year ago, human biochips cost $2,000 per unit. Currently human biochips cost $1,000, while chips for mice, yeast, and fruit flies cost around $400 to $500. The price for human biochips will probably drop to $500 this year. Once all the human genes are well characterized and all functional human SNPs are known, manufacture of the chips could conceivably be standardized. Then, prices for biochips, like the prices for computer memory chips, would fall through the floor.

APPLICATIONS OF BIOCHIP Genomics Genomics is the study of gene sequences in living organisms and being able to read and interpret them. The human genome has been the biggest project undertaken to date but there are many research projects around the world trying to map the gene sequences of other organisms. The use of Biochip facilitate: Automated genomic analysis including genotyping, gene expression DNA isolation from complex matrices with aim to increase recovery efficiency DNA amplification by optimizing the copy numberDNA hybridization assays to improve speed and stringency

ProteomicsProteome analysis or Proteomics is the investigation of all the proteins present in a cell, tissue or organism. Proteins, which are responsible for all biochemical work within a cell, are often the targets for development of new drugs. The use of Biochip facilitate: High throughput proteomic analysis Multi-dimensional microseparations (pre LC/MS) to achieve high plate number Electrokinetic sample injectionfor fast, reproducible, samples Stacking or other preconcentration methods (as a precursor to biosensors) to improve detection limits Kinetic analysis of interactions between proteins to enable accurate, transport-free kinetics

CellomicsEvery living creature is made up of cells, the basic building blocks of life.. Cells are used widely by for several applications including study of drug cell interactions for drug discovery, as well as in biosensing. The use of Biochip facilitate: Design/develop "lab-in-cell" platforms handling single or few cells with nanoprobes in carefully controlledenvironments. Cell handling, which involve sorting and positioning of the cells optimally using DEP, optical traps etc. Field/reagent based cell lysis,where the contents of the cell are expelled out by breaking the membrane,or increase the efficiency of transfection using reagents/field Intracellular processes to obtain high quality safety/toxicity ADME/T data

Biodiagnostics and (Nano) BiosensorsBiodiagnostics or biosensing is the field of sensing biological molecules based on electrochemical, biochemical, optical, luminometric methods. The use of Biochip facilitate: Genetic/Biomarker Diagnostics, development of Biowarfare sensors which involves optimization of the platform, reduction in detection time and improving the signal-to-noise ratio Selection of detection platform where different formats such as lateral flow vs. microfluidics are compared for ease/efficiency Incorporation of suitablesensing modality by evaluating tradeoffs and downselect detection modes(color / luminometric, electrochemical, biochemical, optical methods) forspecific need.

Protein Chips for Diagnosis and Analysis of DiseasesThe Protein chip is a micro-chip with its surface modified to detect various disease causing proteins simultaneously in order to help find a cure for them. Bio-chemical materials such as antibodies responding to proteins, receptors, and nucleic acids are to be fixed to separate and analyze protein.

Fig 1.6 Opportunities for invivo biochip

Fig 1.7 PSM (Physiologic status monitoring) Biochip system

Human interface to BiochipBiochips provide interfaces between living systems and electro-mechanical and computational devices. These chips may be used in such varied applications as artificial sensors, prosthesis, portable/disposable laboratories or even as implantable devices to enhance human life. Biosensor chips can provide the construction of sophisticated human sensing systems such as nose and ears. The second paradigm is chips for sensing biology that will provide for interactions with living bodies and build new diagnosis tools (such as diabetes glucose meters) or new medicines (such as a bio-assay chip). A tiny microchip, the size of a grain of rice, is simply placed under the skin. It is so designed as to be injected simultaneously with a vaccination or alone."The biochip is inserted into the subject with a hypodermic syringe. Injection is safe and simple, comparable to common vaccines. Anesthesia is not required nor recommended. In dogs and cats, the biochip is usually injected behind the neck between the shoulder blades. Trovan, Ltd., markets an implant, featuring a patented "zip quill", which you simply press in, no syringe is needed. According to AVID "Once implanted, the identity tag is virtually impossible to retrieve. The number can never be altered.

Fig 1.8 Human interfacing of Biochip

First Implant of Biochip On May 10 2002, three members of a family in Florida ("medical pioneers," according to a fawning report on the CBS Evening News) became the first people to receive the implants. Each device, made of silicon and called a VeriChip, is a small radio transmitter about the size of a piece of rice that is injected under a person's skin. It transmits a unique personal ID number whenever it is within a few feet of a special receiver unit. VeriChip's maker describes it as "a miniaturized, implantable, radio frequency identification device (RFID) that can be used in a variety of security, emergency and healthcare applications.

ADVANTAGES & DISADVANTAGESAdvantages Biochips promise dramatic changes in future medical science and human life in general. With the advances of bio and nano technologies two strong paradigms of integrated electronic and life are emerging. Ability to detect multiple viral agents in parallel e.g. differential diagnosis of agents from other diseases that cause similar clinical symptoms, or the recognition of complex mixtures of agents. Clarification of syndromes of unknown aetiology. Increase speed of diagnosis of unknown pathogens ("future proofed" surveillance tools). Viral typing (AIV, FMDV, Rabies) Drive policy for diagnostics and disease control. Epidemiological tracing Interagency collaboration.

Disadvantages DNA chip cannot be fabricated at high density and mass production is limited. Meanwhile, the DNA chip and the DNA microarray have different fabrication methods but are similar in that different oligonucleotides are aligned on a square spot having a certain size in a check pattern. The immediate prospects for biochip technology depend on a range of technologic and economic issues.

DEVELOPMENT AND PROJECTS - VIEW OF THE FUTURE 1. Biochip reusabilityCurrent biochips are of necessity disposable, in part because the current devices are not physically robust. For example, nucleic acid probes tend to break away from a supporting glass plate. A decade from now, this problem may have been better addressed, making the chips more reusable, and perhaps at the same time permitting probes with longer spans of genetic data than are feasible today. In this way, a manufacturing improvement might facilitate more powerful forms of genetic analysis. On the other hand, it may be better to manufacture biochips so inexpensive that they can be used once and then discarded.

2. Biochip versatilityCurrent biochips are single-purpose, hardwired devices. Even if future biochips do not become programmable, in the fashion of computer chips, they may become usable for multiple purposes, such as the analysis of a tissue sample for numerous pathogens.

3. Biochip standardization For diagnostic purposes, any medical test should be administered, and its results interpreted, in a standardized way. Beyond that, it seems desirable for biochips performing different tests to have an output detectable by the same readout device. Hence, a race is underway to create a biochip platform or motherboard capable of handling a wide range of biochips, irrespective of the internal details of a given chip's function. In particular, two companies, Affymetrix and Molecular Dynamics, have formed the Genetic Analysis Technology Consortium (GATC) a name that also represents the four nucleotides that carry genetic code in DNA. The hope is to establish industry-wide standards for the reading of biochips

Markets, business issues, development issues, Industrial and research funding issues The definition of bio-microsystems can vary broadly depending on platforms, operation principles, applications, etc. For the purpose of this document, we will assume the definition of bio-microsystems as miniaturized and integrated devices which are used as a tool for biological and biochemical detection, analysis and actuation for use in various applications: research and development, diagnostic, therapy as well as health care monitoring, environment, defence, agriculture businesses.Under the term bio-microsystems, we include devices currently defined as biosensors, micro-arrays, DNA chips, lab on chips, cell chips, bioMEMS, and more recently micro total analysis systems(TAS).

Market segmentationGeneral

Bio-microsystems can be segmented according to: their technological characteristics (incorporation of microfluidics, integrated sensing, etc) the type of biological element studied (DNA, protein, cell, tissue) the application/function and final use (chronic monitoring, one-time testing) the final end user (pharmaceutical, agriculture, cosmetics, etc)

Market segments targeted by bio-microsystemsMarket Potential

In-vitro Diagnostics (IVD) (Genetic or Biochemical tests)such as Point of Care (POC) portable devices for: Clinical Diag.: Glucose & lipid, Immunoassays, Microbiology, Virology Forensic Medicine Veterinary Dg Agro-industrial testing (microbiology, GMO & allergen detection, IP enforcement) Environmental testing (air, water pollutants: metals, chemicals, pathogens)All IVD: 22B$* Glucose Diag. : $5 Billion Cancer Diag. : $1.6 Billion Cardiac Diag. : $1.4 BillionGenetic IVD : $0.66 Billion(as per Clinical Reports 2001)

Water testing: 1.77B$

Med. devices (Diagnostic and Therapy Equipment) such as: Medical Imaging: e.g. in-vivo cameras Monitoring equipment Implantable and portable devices

155 B$

Monitoring equipment Implantable and portable devices High performance analysis systems for biology R&D (pharmaceutical, agricultural and academic) Drug development Gene profiling Proteomics

14 B$ (Drug & Market Dev)0.6 B$ (2002)0.56 B$ Frontline (2000)

Public Security / Defence / Substance Abuse 0.5B$ (CTST 2003) but huge investments in R&D promoting all technological aspects, from microfabrication technologies to integrated systems.

For the purpose of this note, which aims to give growth perspective, we will divide the market based on final targeted application as follows: In-vitro diagnostics as a potential replacement for conventional biologic (genetic,immunoassays, cellular) and biochemical tests. These tests are used today for instance to diagnose diabetes through glucose detection. In-vivo diagnostics and therapy. These bio-microsystems will target the large market of Medical Devices that includes implants, surgical apparatus but also medical consumables such as dressings. Biological R&D applications conducted by academic research institutes as well as industries such as pharmaceutical.The segment of public security (such as bio-terrorism countermeasures) and defence monitoring is considered separately because of its specific requirements and market.The market of bio-microsystems in 2003 was still embryonic and very concentrated around theapplications related to biological R&D; applications related to in-vitro diagnostics were emerging in 2003.

To put the markets (2002) in perspective, these are the individual worldwide shares:Medical devices: $170 billionIVD market: $19 Billion Glucose sensors: $5billion (annual growth >10%) Array: $50 Million (annual growth >10%)Active devices: Pacemakers: $5 Billion Drug delivery: $3 Billion

Biological R&D

We will now consider bio-microsystems used for the R&D application and verify which type of technological solutions they propose to replace and which suppliers in the chain are then involved.Bio-microsystems are targeting the whole biological process mainly for their added value of high throughput, miniaturization, automation and portability.The various steps in traditional biological processes are described in the graph below. It highlights the various technological options utilised but also indicates that the R&D targets end users from different types of industry (pharmaceutical, agro-industrial, environmental, cosmetics).

Fig 1.9 Traditional biological processes

Along this biological process we have very different suppliers (from robotic platform manufacturers to plastic pipettes manufacturers). The graph below presents the suppliers at the different steps of the biological process. We have classified them according to their core activity (for example, Tecan appears under the robot segment even if it also proposes detection instrumentation). Companies such as pharmaceutical industries are involved at 2 levels in the process: they are considered for their own R&D but also as potential users/sellers of drugs developed by this process. A remarkable feature appearing clearly in the table is the strength of big pharmaceutical companies in Europe, and the absence of Europe from the new bio-microsystem technologies, mainly represented by startups in theUS.

Fig 1.10 Suppliers in biological processesMarket size and main actorsThe bio-microsystems market in 2002 is mostly a biosensors market (devices without extensive micro fluidic devices) and includes products that are mainly used for R&D applications. It is estimated to 620 Millions of Dollars by recapturing the sales of major actors (Affymetrix, Agilent, Ciphergen). DNA chips represent today the major type with more than 83 % of sales. Lab on chip is emerging mostly with Caliper sales and represents 10 % of the total. The remainder consists of protein chips (mostly Ciphergen) and other types of DNA arrays.

The medical devices market is estimated to be 170 billion Euro in 2003. The in-vitro diagnostics market was 20billon in 2001 and 37 billon in 2010. The overall growth rate is 7% per annum with the major drivers being: Favourable demographics Improvements in healthcare Innovation and improvements in current technologies

The per capita annual expenditure for health care is approximately $3000 in the U.S., $3200 in Germany, and $ 2000, on average, in Europe. The total world market is estimated at $ 2.8 trillion where individual segments include $140 billion for medical instruments and $400 billion for pharmaceuticals.US companies account for more than 50 % of the total market (43% of the EU market). In some sectors such as cardiovascular the market share of US companies is even higher. The market environment of the medical devices and diagnostics sector is changing: the markets have grown often rapidly in the last few years. Factors for this change vary across individual segments of the sector but common ones include improved sales, market growth, impact of new products and new technologies and price reduction. Likewise, key trends and developments vary but they include price sensitivity, healthcare budgetary constraints and increasing competition caused by mergers and company consolidation (e.g. Johnson and Johnson and De Puy, Boston Scientific and Schneider).Global biochips market is forecasted to reach US$9.1 billion by 2015 with a CAGR of 20.9% during 2009-2015; the massive CAGR is primarily supported by Asia-Pacific followed by the European Union. Among the major industry segments, biochips instruments are expected to exert the highest support to the industry with a CAGR of 22.6% globally. Microarrays segment accounts for nearly 60% of the industry value while instruments, reagents and consumables together indicate approximately 25% of the market value. North America is expected to maintain the highest market share for the biochips industry by 2015; Asian economies are expected to post a large CAGR of 23 percent during 2009-2015. Higher growth rate favors improved industry investments in Asia-Pacific region in comparison with North America and Europe, going ahead. Emerging Market Treds Advancements in the Technological Spaces Market Demand Of The Segments (By-Region) Key Growth Areas and Market Size Region-Wise Demand Factor

Based on online surveys using customized questionnaires by our research team. Besides information from government databases, company websites, press releases & published research reports are also used for estimates. Estimates have incorporated recessionary impact on the biochips industry. Anticipating a protracted recovery towards 2011, we have used CAGR to forecast 2011-2015 figures.

The analysis primarily deals with products, applications, technologies and end-use markets. Further, the subdivided categories include: Biochips Products Biochips Applications Biochips Technologies Biochips End-Use Markets

The period considered for the biochips market analysis is 2009-2015. The region wise distribution of the market consists of North America (USA and Canada), Europe (Germany, France, United Kingdom, Italy, Spain and Rest of Europe), Asia-Pacific (Japan, China, India, South Korea, Australia and Rest of Asia-Pacific) and Rest of the World. Incorporating the recession impacts on the industry, the market growth rate in the major economies such as the U.S., Japan, China etc. are estimated individually for the upcoming years.

More than 600 leading market players are identified and 50 key companies that project improved market activities in the near future are profiled. The report consists of 449 data charts describing the market shares, sales forecasts and growth prospects. Moreover, key strategic activities in the market including mergers/acquisitions, collaborations/partnerships, product launches/developments are discussed.

The evolution of biochips has opened new vistas in the biological systems. In addition, all other sciences are integrated which cumulatively contribute for a big future for biochip industry. The broad life science division has been witnessing a rapid growth and technological improvements varying from sector to sector since the past 3-5 years. Accelerating growth rate exhibited by the biochips industry, even during the recession years, confirms the positive growth prospects going ahead. The field of drug research gets more glamorous with the drug screening at cellular level. DNA microarrays and biochips have created revolution enabling the target validation and drug discovery. Genome scan is very soon going to become an ultimate weapon for diagnosis. In no time all the information related to genes will be sequenced, annotated and completed along with the list of diseases which are susceptible. Day to day the researchers are also making an effort to develop medication to control the various diseases, by using biochip technology. As the applications of biochips are wide both in the research and clinical use, a wide potential market is expected. The emergence of biochip technology can be attributed to a decade which has gradually developed into maturity. This industry is expected to bring rapid and significant changes in the life sciences and medicine. Microarray technology has a great potential and is widely used in DNA and protein analysis.

The sector responses to these changes are: Increased R&D spending; More rapid introduction of new products; Cost reduction in the supply chain; Increased flexibility; Moving to lower cost locations.

In the next 5 years a significant change in the market will be observed, primarily driven by: price pressure; continuing consolidation of companies within the sector; reduced product lifecycles leading to faster new product introduction; technology changes driven by small leading-edge companies; Increased regulation.

Both the Diagnostics and Medical Device sectors have the similar needs and pressures; however, the diagnostics sector is smaller in terms of market size and number of companies.

Several remarks can be made on the above market analysis: it assumes business as usual: it is an incremental steady development and does not consider any breakthroughs in the markets; it does not tell who the players will be; one has to determine how the added value changes and who gets it.

Business issuesAbout value creation:There is no evident to see data that compares bio-microsystems to other diagnostic technologies.Evaluating this item is a rather complex task; for instance, what is the added value of a cell phone for the end user? A major factor in this case is the immediate availability at any nearby shop. There is a technological advantage, a cost advantage, but also the convenience of easy availability to the user. So while choosing a new application, one should look for the whole value chain and whether this application constitutes a real breakthrough.

Molecular Diagnostics value chainBio/marker knowledge & IPR(Bio)content provider

Biomaterials (antibodies) & biochemical processingDisposable

Microfluidics & detection

Reader & signal processingSystem/service provider; application & market access

System integration hospital (workflow) or e-health (homecare) business

Business modelsIn such a chain, added value sharing is not obvious now. In the long run, it might occur that only two players will be concerned, a technology provider and a service provider. As an indication of things to come, one can look at the acquisition of Amersham by General Electric. Expertise of GE in electronics and Amersham in the bio field enables a new enterprise that is able to generate both the content as well as the hardware. So they can capture the whole value chain because they have the bio content and the ability to make a large part of the platform. GE manufactures very complex medical instruments that are used in all hospitals. This is a very interesting and intriguing development that certainly affects the industry. Will microelectronics be just a universal technology provider without any involvement in the biology layer? Will they systematically be involved with biology suppliers? What will be the marketing strategy?A major issue in the markets (and how businesses will operate) is the role of the government and healthcare organizations. The reason why a lot of companies are moving to the Unites States is because there they can expect returns more easily than in Europe. Therefore, actions on hospitals, social security, complementary insurances, etc will be necessary in Europe.

Although the US is still a major player, it is also important to observe the emergence of othercountries, in particular from Asia. In a market where small companies abound, it is conceivable that many of them will emerge from unexpected countries, in many cases facilitated by local regulations.

Intellectual property rights issues

IP rights play a very important role in the emerging bio-microsystems industry, with severalcompanies pursuing aggressive positioning. Since the industry has been so far mostly venture-capital funded, with valuations based more on potential (often determined by patents) rather than actual businesses, little incentive has been present for cross-licensing and cooperative agreement.As a result, frequent litigation has been the norm. Higher profile cases have included the Affymetrix vs. Oxford Gene Technology and the Nanogen vs. Combimatrix legal skirmishes, both now settled. Our forecast is that the actual introduction of the first products in the market, and pressures coming from investors to settle pending litigation, will have an effect on the industry, with an increase in cross-licensing and agreement, but a level of litigation unusual to the semiconductors and electronics industry is still expected.

Some of the most relevant portfolios include: London-based OGT, which by now appears to be devoted mainly to the commercial exploitation of its IP base. Affymetrix, which has complemented its existing portfolio via acquisitions Nanogen, which has a number of relevant patents, the most interesting likely being those related to electronically assisted hybridisation.

On a separate note, we could mention the Roche PCR patents and alternative amplification systems,e.g. Becton Dickinsons SDA technology.A large number of other players are also involved, almost all of them US-based, so that at the moment the only significant patent portfolio in Europe appears to be that that of OGT. It is worthwhile mentioning that only research teams with a multidisciplinary approach have the ability to write strong patents at system and application level rather than at technology level only. The European weakness in this field of multidisciplinary organizations is limiting its ability to build a strong patent portfolio.

A business analysis centred on pros/consIn order to identify the driving forces and roadblocks to large-scale marketing of bio-microsystems market studies usually do not have much to add in situations of emerging technologies/markets. It is then useful to analyse the pros/cons for the mass production of bio-microsystems. We will concentrate on the medical market, the other ones (agriculture, environment and security) being more suitable to standard analysis. The key aspect is the occurrence (or lack thereof) of a major breakthrough in diagnostics and monitoring systems, implying multi-million sales for given devices.

The pro arguments Present research work confirms the need for parallelism, high speed, and functionalintegration. Bio-microsystems are indeed capable of it, but they cannot yet demonstrate a significant (and decisive) cost reduction in healthcare. Most urgent needs are those related to the focused monitoring of chronic patients which could employ tethered bio-microsystems, or through implants that would combine monitoring, stimulation and drug release. Low invasiveness means that patients will be able to carry out tests themselves. This may lead to new markets, such as systematic tests (associated to specific chronic diseases or preventative monitoring in certain age groups) to appear. Similarly, this could have an outstanding impact in the current trends of auto-medication. These markets do not exist today because such tools still do not exist, but they may be addressed by bio-microsystems. Timing is a big advantage DNA Array tests for Diagnosis: Translates into lower Mortality, less Time, lower Cost Conventional Process: Diagnosis: 3 days (Treatment: broad spectrum antibiotics) then revise therapy DNA Diagnostics: 0.5 to 1 hour then targeted antibiotic treatment begins immediately; this speed lowers total cost of diagnosis & improves therapy decisions. Detailed monitoring can be done on a daily basis.

Niche markets: Bio-microsystem could allow you to obtain a necessary profile with several hundred analytes. Unlike those situations where bio-microsystems are competing against more traditional techniques, exploring these markets can make a strong case for the establishment of bio-microsystems as a competitive technology in a broader scenario. A good example is that of blood donation screening. Actually, in all developed countries blood transmitted infectious diseases testing is achieved by real-time PCR analysis in a (8-16 member) blood pool. In this way a number of viruses (HIV, HCV, HBC) can be easily detected. There is a real market and a real demand to make this blood testing more rapid, more sensitive, by moving from pool to single unit testing. The sensitivity issue is of paramount importance; low contamination is still difficult to detect in pool samples and ideally the test should be extended to a larger number of pathogens. This is a real need that is very difficult to address, but we can explore the use of microsystem-based multiplex PCR to achieve those objectives. Issues would include detection sensitivity, reliability, traceability requirements, etc. The other reason for this to be a good application is that the prescriber is also responsible for the costs. However, the blood donation is one of the fields of high regulation because of the consequences of an eventual contamination. Defence against biological warfare. Following the announcement by ST Microelectronics of the prototype PCR chip a year ago, they got independent requests from various defence ministries. They all have their own ideas for developing a portable cDNA detection system with highly integrated devices. While the defence markets may never be large, they could be decisive in the development of the technology in its nascent phase, as occurred for microelectronics.The con arguments Drug markets increase at a faster speed than diagnostics, which makes resources lessavailable for bio-microsystems. These new technologies cannot by themselves create a huge new market. Its not somuch a technology that drives a market than how many physicians prescribe how many tests. Something will happen to these technologies if we find the niches. We also need to satisfy the following criteria:1. Reliability of the assay, specificity, sensitivity, false negative and positive values percentage2. Easy automation3. Large product range (Investment for expensive equipment for manufacturing isimpossible without significant product range). Medical practice still relies on more traditional methods. Following clinical examination, a patient is sent for laboratory tests and based on the results a given drug is prescribed Decades ago it was predicted that home tests would revolutionise medicine, which did not happen. Despite isolated successes such as the home pregnancy test and urine dipstick tests for clinical use, there is resistance against the introduction of such techniques even when the technology is sound, as it happened with the dipstick staphylococcus test 20 years ago. The massive generation of information, which is one of the strengths of biomicrosystems, is by itself also a problem. The value of such volume of information is in many cases arguable. Unless some intelligence is added to the system, allowing the information to be adequately processed, the usefulness of the data is questionable. Additionally, there are ethical and psychological issues to be considered as the patient has direct access to the information or it is made available outside the clinical setting. The medical community tends to resist against the introduction of certain new technologies, as was the case with information technology. However, if it is costeffective to the social security system it may be seen differently.

Issues in biochip development1. Time framesBio-microsystems industry is characterized by a typically long timeframe. Ideally we should find specific niches that will trigger the investment process and allow the industry to continue its expansion in other directions.Market size is also of concern. In the early 80s it was thought that diagnostics would be a booming market, but 20 years later it is still around the mark of $10 Billion in sales, even with a growth rate of30% a year and a growth expectancy of another 20 years.We should expect that many biomedical applications will continue to be developed using other technologies and later transferred to a bio-microsystem platform. It remains to be seen how some of the major testing techniques will undergo this process (given that most of the biology development has already been done) and who will pay for it. There has been some progress at the research level, where genetic or protein profile analyses have been correlated with the clinical status of patients affected with multigenic or complex diseases. An interesting example is that of prostate cancer: current PSA testing cannot help differentiate between prostatitis and prostate cancer when the PSA result is in the low range. One team of the National Cancer Institute in the USA has demonstrated that an accurate diagnosis can be established upon protein profile analysis by mass spectrometry. While there is a lot of debate on the use of such an approach, the real question still is whether we can translate this genetic and/or protein profile analysis into real diagnostic tools

2. Cultural issues between industriesCollaboration between electronics and pharmaceutical/diagnostic companies is difficult as a result of fundamental differences in IP policies, where the electronics industries tend to share and give licenses and the pharmaceutical/diagnostic companies tend to block and protect their areas of interest. In European projects participating of the FP6 framework this has already led to insurmountable difficulties and the withdrawal of at least one Integrated Project.What is needed is a change or evolution of cultures, from autarchic to open cooperative companies. It will be a new type of business, mixing bio and micro, with very different cultures.

3. StandardsIn the gene profiling there are rather well established procedures such as confocal microscopy,fluorescent detection. For proteins, the mechanisms will be completely different, requiring for instance choices of ligands and transducers. Overall the technology in the proteomics domain is comparatively poor. There are not yet technologies that really answer existing needs. As we are still in the infancy phase of a new technology, when many technologies compete, it is difficult to progress, in particular as funding appears to have a very uncertain return. Conversely, how many technologies will survive to fulfil the various needs?How will we reapply the same platform for several users and several bio-companies? Is it even reasonable to consider such a thing? How can we share a given technology between users? The customer (diagnostics labs, hospitals, doctors, patients) would also like to have the same platform for different applications/tests. One will also need to answer validation issues for specific applications (prostate cancer, IVD, AIDS, blood screening, etc). How will We show/demonstrate the sensitivity, specificity, reproducibility, linearity, etc. before going to market? Even after that we will need the transition to the real product (packaging problems,handling etc). One critical point when we contemplate the diagnostic field is that it is highly regulated. One has to demonstrate (to the FDA, as well as to the European regulatory authorities) that any new technology is sufficiently accurate and reliable. Additionally, the end users must be confident with the provided results. This can only be achieved by incorporating some internal controls and by implementing a right QC strategy (starting from the design phase up to the manufacturing step) to be sure that these new technologies or new devices have reached the required level of reliability.

4. Funding issuesWe have observed the disappearance of venture capital in the starting phases, which in part is explained by the early demise of related technologies. At the moment in the US there is huge federal funding (through usual channels, plus the Department of Homeland Security). It creates a large funding imbalance, and distorts competition in an emerging field that cannot be self-funded. On the other hand, the fragmentation of the European market, the variety of social security systems and of national regulatory agencies makes it much more difficult for industries to operate in Europe. Even though the defence/security needs may not create a mass market for devices (as did the space and defence systems of the 60s and 70s for microelectronics) they will create the technology base for the industry. The US government is driving the advancement of diagnostics devices in particular, because it is clearly advantageous to have standalone autonomous detection instruments.

Due to these factors, many European companies have already moved their research labs to the US, due to a number of converging factors: federal funding, large base for possible cooperation with wellequipped and staffed university labs, leading market in innovation; this inevitably gives US-based companies and start-ups a competitive advantage. In addition to federal funding opportunities, the healthcare market is very innovative and looking for cost-effective solutions; this means that newly introduced technologies in the US will stand a much higher chance of fast success and investment return.

CHAPTER 3METHODOLOGY3.1 Type of projectThis is an exploratory study of devising an innovative instrument named biochip in human being for diagnostic purpose. Exploratory study is the identification of researchable problem.3.2 Target RespondentsThe target population for the study will Patients and normal people from different localities of Chennai.3.3 LimitationsThis project will be limited with respondents in Chennai and study on possibility of devising such a technology for therapeutic purpose apart from current applications.3.4 Sampling MethodsConvenience Sampling, a non-probabilistic unrestricted sampling technique is the sampling technique which will be used for this study. That is, a sample population selected because it is readily available and convenient. Here the sample population are meted in person.3.5 Data ProcessingThe data required for study are obtained through primary and secondary data collection method. Primary Data will be collected by administering questionnaires to the selected samples from target population and secondary data from journals, magazines and Internet.An appropriate sample size in the range of 100-145 will be selected depending on the allowable error and confidence level chosen. The selected sample size will be distributed across different localities of Chennai.

3.6 Tools of Analysis The method used here for analysis of data are Percentage AnalysisPercentage Analysis refers to a simple ratio used to make comparison between two or more series of data. Since the percentage reduces everything to a common base and thus meaningful comparison could be made and can be used to describe relationships. The formula used is given as: No. of respondents of a particular option _______________________________________ x 100 Total No. of respondents

Chi-Square test

Chi-square test is a statistical test used to compare observed data with data we would expect to obtain according to a specific hypothesis. The chi-square statistic 2 is given by the sum of the squared difference between observed (O) and expected (E) data, divided by the expected data in all possible categories.

It is represented by the following formula:2 =(O-E)2/E

ANOVA (Analysis of Variance)

The terms Single Factor Analysis of Variance, Single Factor ANOVA, One Way Analysis of Variance, and One Way ANOVA are used interchangeably to describe the situation where a continuous response is being described in terms of a single factor composed of two or more levels (categories). It is a generalization of Student's t test for independent samples to situations with more that two groups. ANOVA provides a statistical test of whether or not the means of several groups are all equal, and therefore generalizes t-test to more than two groups.ANOVA is used to test hypotheses about differences in the mean between two or more groups. ANOVA is used to compare multiple groups of observations. ANOVA examines how independent variables affect a dependent variable.Respondents considered normal people and patients with diabetes from localities of Chennai. Random sampling ranged around 193-205 was taken.

CHAPTER 4DATA ANALYSIS AND INTERPRETATION1) Respondents age groupS.NoParticularsNo of RespondentsPercentage

1506834

Total205100

Inference:From the above chart, it is found that 9% of the respondents are aged 50.2. Type of respondentsS. NoParticularsNo of RespondentsPercentage

1Diabetes14775

2Non-diabetes5525

Total205100

Inference:From the above chart 75% of the respondents said suffered from diabetes and 25% of the respondents said not suffered.

3) Percentage of diabetic patients S. NoParticularsNo of RespondentsPercentage

1>1 yr4228

21 2 yrs4127

32-3 yrs2214

43-4 yrs2013

5