Biochips - Seminar Paper

Biochips were invented  9  years  ago by gene scientist Stephen Fodor . In a flash of light he saw that photolithography, the process used to etch semi conductor circuits in to silicon could also be used to assemble  particular DNA molecules on a chip.
     The   human  body  is the  next  biggest  target  of   chip  makers  . medical  researchers   have  been  working  since  a  long  period  to  integrate humans  body   and  chips  . In  no  time  or  at  maximum  within  a  short  period  of  time  Biochips  can  get  implanted  into  the  body  of  humans  . So  integration  of  humans  and  chips  is  achieved   this  way  .
          Money  and  research  has  already  gone  into  this  area  of  technology  .Anyway  such  implants  are  already  being  experimented  with  animals  .


            A   biochip  is  a  collection  of   miniaturized   test  sites (microarrays)
    Arranged  on   a  solid  substrate  that  permits  many  tests  to be  performed
    At  the  same  time  inorder  to  achieve  higher  throughput   and   speed  .
    Typically  a biochips  surface  is   no larger  than  a  finger  nail  .   Like
    A  computer  chip  that  can  perform  millions  of mathematical  operations
    In  one  second , a  biochip  can  perform  thousands  of   biological  reactions
    Such  as  decoding  genes , in   a   few  seconds  .
                A  genetic  biochip  is designed   to  “freeze”   into  place the  structures  of   many   short  strands  of  DNA ( deoxyribo  nucleic  acid )  ,  the  basic  chemical  instruction   that  determines  the  characterstics  of  an  organism  . effectively  ,  it is  used  as  a  kind  of  “  test  tube  “  for  real  chemical  samples.  A  specially  designed  microscope  can  determine  where  the  sample  hybridised  with  DNA  strands  in  the  biochip. 


             The  chips  are  of  the  size  of  an  uncooked  grain  of  rice  small  enough  to  be  injected  under  the  skin  using  a syringe  needle  .  They   respond  to  a  signal  from  the  detector  ,  held  just  a  few   feet  away  by  transmitting  an  identification  number  . This  number  is  then  compared  with  a  database  listing  of  registered  pets  .

                      Hausdorffs  chips  are  external  ,  but  another  chip  currently  under  development  will  be  injected  under  skin  . The   chips  will  allow  diabetics  to  monitor  the  level  of  sugar  glucose  in  their  blood . Diabetics  currently  use  a  skin  prick  and  a  handheld  blood  test  and  then  medicate  themselves with  insulin  , depending  on  the  result  .  The  system  is   simple  and  works  well ,  but  drawing  blood  each  time  is  pain full  so  patients  donot  test  themselves  as  often  as  it  is  needed .

                      The  new  s4ms  chip  will  get  underneath  the  skin  sense  the  glucose  level  and  send  the  result  back  by    radio  frequency  communication. A  light  emitting  diode  starts  of  the  detection  process . The  light  that  it  produces  hits  a  fluorescent  chemical :  one  that  absorbs  incoming  light  and  re emits   it  at  a longer  wavelength . The  longer  wavelength  of light  is  then  detected , and  the  result  is  sent  to  a  control panel outside the body . Glucose is detected, because the sugar reduces the amount of light that the florescent chemical  re emits . the more glucose there is the  less light that is detected.
                                    S4MS is still developing the   perfect fluorescent chemical, but the key design innovation of the S4MS chip has been fully worked out. The idea is simple : the LED  is sitting in a sea of the fluorescent molecules. In most detectors the light source is far away from the fluorescent molecules, and the inefficiencies that come with that mean more power and larger devices. The prototype S4MS chip 22mW LED, almost 40 times less powerful than the tiny power on buttons on a computer keyboard. The low power requirements mean that energy can be supplied from the outside, by the process called induction. The fluorescent detection itself does not consume any chemicals or proteins, so the device is self – sustaining.


                The  civil debate  over  biochips  has  obscured  their  more  ethically  benign  and  medically  useful  applications . Jeffery  housdoff  of  the  Beth  Israel  deaconess  medical  center  in  Boston  has  used  the  type  of  pressure  sensitive  resistors  found  in the  buttons  of  a microwave  oven  as  stride  timers .He  places   one  sensor  in the  heel  of  a  shoe  and  other  in  the  ankle  and  adds  a  computer  to  the  ankle  to  calculate  the  duration   of  each  stride(step).
             Young  healthy  people  can  regulate  the  duration  of  each  step  very  accurately  , but  elderly  patients  prone  to  frequent  falls  have  extremely  variable  stride  times . by  using  this  information  doctors  can  change  their  medication  and  ask  them  to  do  exercises .  Hausdorff  is  also  is  also  using  the  system  to  determine  the  success  of  treatment  of  congestive  heart  failure  .  By  monitoring  the  number  of   strides  that  a  person  takes  , he  can  directly  measure  the  patients  activity  level  , by  passing  the  often  flawed  estimate  made  by  patient . 

Oxy sensors

                                The working model of  an oxygen sensor uses the same layout. With its current circuitry it is about the size of a large shirt button, but the final silicon wafer will be less than a millimeter square. The oxygen sensor will be useful not only to monitor breathing in the intensive care units, but also to check that packages of food or containers of semi conductors stored under nitrogen gas, remain air tight.
                                Another version of an oxygen sensing chip currently under development sends like pulses out into the body. The light is absorbed  to varying extends, depending on how much oxygen is being carried in the blood, and this chip detects the light that is left. The rushes of blood pumped by the heart or also detected, so the same chip is pulse monitor. The number of companies already make large scale versions of such detectors.
            This oxygen chip is perhaps about two years away, but the dimensions of another temperature – sensing chip has been reduced to 3mm per side. The transition of certain semi conductors to their conducting state is inherently sensitive to temperature, so designing the sensor was simple enough. With some miniature radio frequency transmitters, and foam rubber earplugs to hold the chip in place, the device is complete. Applications range from sick children, to chemotherapy patience who can be plagued by sudden raises in body temperature in response to their anti cancer drugs.

Brain Surgery with an on off  switch
            Sensing and measuring is one thing, but can we switch the body on and off? Heart pace makers use the crude approach : large jolts of electricity to synchronize the pumping of the heart. The electric  pulses of the Activa implant, made by US – based medtronics or directed not at the heart but the brain, they turn off brain signals that cause the uncontrolled movements, or tremors, associated with diseases  such as Parkinson’s.
            Drug therapy for Parkinson’s disease aims to replace the brain messenger, dopamine, the product of the brain cells that are dying. But eventually that drugs affects wear off, and the erratic movements come charging back.
            The activa implant  , cleared for use in the US in AUG, 1997 is a new alternative that users high frequency electrical pulses to reversibly shut off the thalamus. The implementation surgery is far less traumatic than thalamotony
And if there are any post operative problems the stimulator can simply be turned off.  The implant primarily interferes with aberrant brain functioning.

Adding Sound To Life
            The most ambitious bio engineers are today trying to add back brain functions, restoring sight and sound where there was darkness and silence.
The success story in this field is the cochlear implant. Most hearing aids are
Glorified amplifiers, but the cochlear implant is for patients who have lost the hair cells that detect sound waves.  For these individuals no amount of amplification is enough.

            The cochlear implant delivers electrical pulses directly to the nerve cells
In the cochlea, the spiral-shaped structure that translates sound into nerve pulses.  In normal hearing individuals, sound waves set up vibrations in the walls of the cochlea, and hair cells detect these  vibrations.  High frequency noises ( deep notes) vibrate the base of the cochlea, while low frequency notes vibrate nearer the top of the spiral.  The implant mimics the job of the hair cells.  It splits the frequencies of incoming noises into a number of channels ( typically eight)
And then stimulates the appropriate part of the cochlea.

Clarion ‘ and ‘Nucleus’
            the two most successful cochlear implants are the clarion ( developed at the university of California at San Francisco (UCSF) and Advanced Bionics Corporation of Sylmar in California)  and the Nucleus ( developed at the University of Melbourne,Australis, and made by cochlear of Sydney, Australia).
Upgrades largely focus on improving the speech processing software, which is operated by a minicomputer worn on the patient’s belt.  Theoretically, increasing the number of channels( and electrodes) could improve sound perception.
But speech is perceived in an area of the cochlea only 14mm long, and spacing the electrodes too close to each other causes signals to bleed from one channel to another.
            The result is a broad brush version of hearing.while some recipients of the devices report speech like sounds,many characterise their new world as being populated with quacking ducks or banging garbage cans. But the success is undeniable.currently two thirds to three quarters of patients (with more recent models) can understand speech  without lip reading says Steve Rebscher,a member of UCSF team.”its pretty  amazing , and certainly better than a lot of people anticipated these devices would do”.        
                               With the ear atleast partially conquered , the next logical target is the eye. Several groups are working on implantable chips that mimic the action of photo receptors , the light sensing cells at the back of the eye. Photo receptors are lost in retinitis pigmentosa , a genetic disease,and in age related macular degeneration , the most common cause of lost sight  in the developed world. Joseph Rizzo of the Massachusetts eye and ear infirmary , and john Wyatt of the Massachusetts  institute of technology have made a twenty electrode,1mm square chip,and implanted it at the back of rabbits eyes.

          The original chip,the thickness of human hair,put too much stress on the eyes the new version is ten times thinner. The final set up will include a fancy camera mounted on a pair of glasses.The camera will detect and encode the scene,then send it in to the eye as a ;laser pulse,with the laser also providing the energy to drive the chip.
           Rizzo has confirmed that his tiny array of light receivers(photo diodes) can generate enough electricity to run the chip.He has also found that the amount of electricity needed to fire a nerve cell into action is about hundred fold lower in the eye than in the ear,so the currents can be smaller,and the electrodes more closely spaced.
         For now,the power supply comes from a wire inserted directly into the eye and ,using this device , Rizzo has detected signals reaching the brain. Eugene de Juan of Johns Hopkins Wilmer eye Institute is trying to answer that question by using human subjects.His electrodes , inserted directly in to the eye , are large and some what crude .But his results have been startling . Completely blind patients have seen well defined flashes, which change in position and brightness as De Juan changes the position of the electrode for the amount of current.
           In his most recent experiments , patients have identified simple shapes out lined by multiple electrodes . With as little as an 8x8 array , de Juan believes he could approximate character recognition, and a 25x25 array might give a crude image.
           The big money in eye implant is in Germany , where the government has pledged  millions of US$.One is similar to the US projects in which chips are implanted on the surface of the retina,the structure at the back of the eye.the other project is putting its implants at the back of the retina where the photo receptors are normally found.These “subretinal”  chips may block the transport of oxygen and food to the overlying nerve cells,  so Everhart Zrenner of the university of Tubinger of Germany is developing  ‘chain mail’ electrode arrays, with plenty of holes for the delivery of supplies.

                  As tuberculosis threatens to make its come back  shrouded in a drug resistent form ,a new biochip technology developed by Argonne National Laboratory and the Russian Academy of Sciences’ Englehardt  Institute of Microbiology, may help stem a global epidemic.
                   In October, Argonne will begin testing its biochip’s ability to distinguish between different TB strains.l The tests will be done on harmless segments of genetic material removed from TB bacteria.
                   The biochips are designed to carry out thousands of biochemical reactions simultaneously, and have performed well in laboratory tests. “But this will be their first test in the realm  of real-world medical diagnostics.
                    They chose TB for the test because new drug resistant  strains have sprung up in Russia and can easily spread to the whole world, including US.If they can quickly identify specific strains, it will help doctors prescribe the best
Treatments quickly and possibly help prevent a world wide academic.
                     According to World Health Organization, TB kills more youth and adults than any other infectious disease, including  AIDS and malaria combined.
 Every year, 7 to 8 million people become sick with the disease.
                     Today, TB patients are often prescribed several antibiotics simultaneously because it takes weeks or months to identify specific TB strains, and patients can die during this time. “If our biochip can do the job,” “physicians can prescribe the most effective treatment without delay.”
                     If successful, these initial studies will set the precedent for similar evaluations of other bacterial and viral diseases.

                    Antibiotic resistance results from the natural selection of stronger bacteria over  weaker ones. Stronger bacteria have mutated genes that confer antibiotic resistance.

                    Because TB cells grow slowly,antiobiotics must be taken daily  for atleast six months to ensure that all the bacteria are eliminated.If treatment is shortened  or inconsistent, surviving bacteria-those most resistant to the treatment-can reproduce, passing their resistance on to their offspring.
                    In impoverished nations, where people cannot afford months of medication, victims effectively become incubation chambers for new drug-resistant strains. In some Russian institutions, roughly 80 percent of the TB patients were found resistant to atleast one antibiotic, and 50 percent showed multiple resistance.
                     Although airborne, TB is not remarkably contagious compared to other viral and bacterial infections. With only one exposure, the body’s defenses normally keep the bacteria at bay, unless the immune system is weakened by a disease such as AIDS. However,with continued exposure, as when living with a person with active TB, someone can develop the disease quickly.

                     Like computer chips, which perform millions of mathematical operations a second, Biochips can perform thousands of biological reactions in a few  seconds.
                     The Argonne/Englehardt biochip is essentially a glass side containing up to 10,000 tiny gel pads, each serving as a mini test-tube.  Attached to each gel pad is a short strand of DNA, the unique set of blueprints that determine the building blocks of every living species. The information in DNA is encoded in long sequences of four molecular units, or bases – adenine(A), cytosine(C), guanine(G) and thymine(T). The precise pairing of A on one strand with T on another strand and G with C, allows DNA to form it’s “double helix”.
                       By fixing only one strand of the double helix to each gel pad, the  chip employs the natural tendency of each DNA base to pair with it’s complementary base. When tests begin, a sample of unknown single strands of TB DNA will be spread on a chip and allowed to naturally pair up with single strands of known TB DNA already in the gels. A direct match will identify drug resistant TB strains.                      
                        By changing the  DNA samples in the gels, scientists can also  use this technique to diagnose a unlimited range of other diseases quickly and efficiently.
                        One of the biggest advantages of Argonne’s  Biochips, over conventional Biochips,  is that they can be cleansed and reused up to 50 times, making them more economical than conventional biochip technology . Also, the gel’s greater size allows them to hold up to 1,000 times the material, making them more sensitive than any other biochip.
                          In standard TB diagnostics, a patient must endure a number of tests. First, a skin test is done to determine if they had ever been exposed. Second, a chest X-ray is done to determine if TB has damaged any lung tissue. Finally, a throat culture is done to determine if the TB is still growing and what antibiotics it resists. Results from the throat culture alone can take a month.
                          “With the advanced biochip technology, we’d be able to get all information we need in a couple of hours”, “Without any false positives.”

                           The researchers have reason for being optimistic about this project. “The fact that it has worked in one sample and it wasn’t difficult to perform, shows us that this has a lot of potential,” . “The current round of tests will tell us more.”
                            However, bringing the test into the clinical setting is another giant leap. “We’re using DNA , not actual fluid from patients,” “But it does give us a good idea of the direction we want to go.”
                            If successful, they would move to a larger scale study with more patients and more conditions and then try to get it to work using fluid samples from active TB patients.
                            “We’ll be doing a full scale clinical diagnosis bit it’ll take years to get to the market,” “Considering that TB is becoming a global epidemic, some urgent steps must be taken to speed up the process. The first step is to figure out if this has a chance to work.”

Implantable Biochips and The End of Human Freedom and Dignity exposes the government plot to wield this invasive, life destroying technology.  Texe Marrs quotes an executive officer of the World Future Society ( 27,000 influential members) as saying : “A biochip implant could be used in a variety of human applications… A number could be assigned at birth and follow that person throughout life ..It would be implanted on the back of the right or left hand so that it would be easy to scan at stores. The biochip implant could also be used as a universal type of identification card”.
A top White House official addressing a high tech conference sponsored by IBM, stated : “The smart card is a wonderful idea, but even better would be a chip in your ear.. We need to go beyond the narrow conceptualization of the smart card and really use some of the technology that’s out there”.
            Science News, an authoritative scientific journal, reports that, “New electronic techniques have been developed to eavesdrop on the brain.  The technique allows outsiders to influence the person’s brain cell conversations and to talk directly with the individual’s brain neurons”.
            The Wall Street Journal says that a U.S. Naval research laboratory, funded by intelligence agencies, is now able to unite living brain cells with microchips.;  some authorities fear that the Defense Departments  intend to produce an  “army killer zombies !” One army expert alarmingly calls the new biochip implant a “Frankenstein _ type weapon”.

        Media Medical And Industrial Complex  had a long term plan  to implant subcutaneous  microprocessor for  a  variety of  help , entertainment   and  communication  purposes  by  acclimating  a generation  of prospective  customers  to  such  skin  altering  conditions.companies  are  seeding  the  market  for  their  future  offerings.
               This  is  the  stuff  of  science  fiction,but  serious  medical  researchers  are  developing  chips  with  tiny  doses  of   medication  that  can  be  dispensed  automatically,without  the  patient  having  to  measure  a  dose  or  remember  to  take  it  at  regular  intervals.
The  recent   attention  to  bioinformatics    rekindles  the  imagination  about  where  such    blend  of  bioscience  and  infotechnology  may  take  us. Adrenaline  and BMSG  will  provide  a  due  diligence  service  for  investors  and  biotech  companies  ,offering  independent  analysis  of  ventures  into  bioinformatics,which  they  define  as  the  art  and  science  of  using  computational  tools  to  find  answers  to  biological  questions.In  other  words  they  are  looking  at  near  term  projects   such  as  Genome  and  Molecular  biology  research  as  well as individualized  medicine.Their  collaborative  work  will  help  scientists  and  it  professionals  use  data  mining  and  knowledge  management  and  process  management to  investigate  biological  frontiers. Vital  stepping  stones  but  not  wondrous  or  delicious  as  the  future  potential  applications  of  bioinfotech.
          Looking  future  ahead  when  implanted  chips  are  programmed  with 
telecommunications  capability  they  can  open  new  connectivity and
entertainment  options . Preserving  that the  first  chips  are  ‘receive  only’.They  would  become  the  ultimate  pagers :  delivering  a  unification  or  internal  ‘ping’  directly  to  human  neurons.
       Eventually  entertainment  providers  will begin to  exploit  this  capability  ,sending  music or visceral  experiences  directly  through  chip.some  programming  may  be  tied  to  video  shows  , giving  you  the  mosh-pit  experiences  while  watching  MTV  or  feeling  the  polar  freeze  while  a  discovery  documentary  about  Antarctica.More  probably  porn  merchants  will be the  first  to  capitalize on  such  in  body  experiences.So that  watching  a playboy  channel show  could  also  trigger  the  appropriate  internal  response among  chip  equipped  viewers.
          Later the  implemented  microprocessor  will  be  upgraded to  two  way  capacity  transmitting  internal  data  back  in the appropriate  network  through  a  wireless  feed.The  medical  monitoring  opportunities  are  immense  but  so  are  the  tracking  capabilities.It is  the  ultimate  loss of  personal  privacy  when  your  body  is  sending  signals  about  where  you  are  and  what  you  are sending.?
Several other  roots    towards  bioinfotech  connection  are  already  being  followed.Predictive  network  of  Cambridge  is  developing  biometric  system  used  to  identify  which  individuals  interface  with  computer  and  media  devices.Predictive  networks  is  monitoring  personal  usage  patterns  (how  individuals  use  specific  keys  and  buttons  ,including  the  speed  and  measure  of  finger  close) to  identify  and  categorize  customer.Although  it’s a  major  leap  from  such tracking  of    external  behaviors  to  inserting a  microprocessor  under  the  skin,  the  eventual  outcome  could  be the  same:data gathering  and  response  based  on  physical  connection  and  the  response.
    Bio-infotech  seems  to  be  a  promising  sector  for the region-even  across-river  opportunity  that  would  combine  the  bio-medical  resources in  Mary  land  with  the  Infotech strengths  of  Virginia .

     If  people  feel  that  they  loose  their  privacy  because  of  Biochips, they  may  resist  use  of it.But  if  they  feel  that  it  could  help  in a lot  of  ways   like  detecting,minitoring and  curing of  diseases  they  can  use them  intensively.
So it is  users of chip  who  determine  its  future  .

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