The microchip at 50: its medical triumphs to date

As last year marked the 50th anniversary of the microchip, Laboratory News investigates the microchip’s potential in the world of medicine, including restoring vision to previously blind patients

The first silicon integrated circuit, more widely known as a microchip, was patented by Robert Noyce in 1951. Since then, the microchip has provided the infrastructure to almost every aspect of modern society, having been miniaturised and cheapened through mass production. It has revolutionised the development of electronic gadgets such as computers, mobile phones and controls for automobiles thanks to its rapid evolution. However, these days the humble chip is often consigned to the background, merely drones which drive industries such as healthcare, telecommunications, automotive, media and logistics. Some critics have argued that the microchip may have even reached its limits as dual processing becomes more common.

In 1965, Gordon Moore¹, founder of Fairchild Semiconductor, predicted “Integrated circuits will lead to such wonders as home computers, automatic controls for automobiles, and personal portable communications equipment,” way ahead of its time.

He continued: “Machines, similar to those in existence today, will be built at lower costs and at faster turnaround,” which also became the reality of how microchips are used today. However, his theory known as Moore’s Law did not predict their application in medical treatment.

Pet owners were the first to benefit from the use of microchips when they were introduced to aid the identification of domestic pets, namely dogs. The electronic tag, inserted under the skin, stores information about the pet’s owner with contact details and has transformed the way pet charities, such as the RSPCA, reunite lost pets with their owners. Additionally, when scanned with an electronic reader, all the pet’s details can be accessed, including their vaccination data helping customs officials at border controls.

In 2006 stories surfaced among the media about humans being subjected to compulsory microchipping by 2016². Dr David Murakami Wood, Managing Editor of the journal Surveillance and Society, claimed that our every movement, purchase and communication could be monitored through Radio Frequency Identification (RFID) that is currently used in new UK passports, Oyster Cards and pet identification chips.

This method of human tracking has already been trialled in mentally-ill patients in the US. An implantable patient tracking system, hosted on a microchip under the skin, gained FDA approval to store health information. The chip, known as VeriMed, contains a unique number that emergency service personnel can scan to retrieve essential medical history information.

Novartis announced trials of a microchip fitted in the patient’s shoulder to act as a reminder to take their medicine. If the medicine is not taken at the correct time, a text is sent to the patient’s carer to remind them. Other drug companies have produced microchips designed to monitor diabetic patients’ glucose levels.

Such applications have been deemed the Big Brother tools of medicine by some sceptics; however it is without doubt that medical professionals are turning to microchips more and more to undo the damage caused by diseases.

Perhaps one of the most exciting applications of microchips in medicine is the development of artificial vision for patients blinded by retinitis pigmentosa. Affecting approximately 300,000 people in the world, retinitis pigmentosa (RP) is one of the most common forms of inherited retinal degenerations that worsen over time. This progressive condition typically causes severe vision problems in adulthood, often resulting in complete blindness.

There are currently two approaches to retinal implants – the subretinal and epiretinal approach. The main difference between these two approaches is the location of the microchip. Subretinal implants are placed below the retina, specifically in the macular region, and perform in-line with the natural processing of images in the human brain. In recent years scientists have come to agree that the positioning of subretinal implants, where light-sensitive photoreceptor cells are located, produces more positive results for patients. Vision is restored as the eye moves allowing for the immediate focus and recognition of items in the patient’s field of vision. The location also allows for superior stability, meaning the chip is unlikely to loosen over time.

In 1996, Eberhart Zrenner, professor of ophthalmology and director of the Institute for Ophthalmic Research at the University of Tuebingen in Germany, developed the first subretinal microchip. Zrenner and his research team designed the chip to imitate the eye’s natural processing of light. His team designed a 3 x 3 mm² array containing 1,500 electrodes to stimulate the damaged cells using pulsed, light-dependent electrical stimuli. This stimulation triggers the perception of artificial light phenomena. This process resembles that of which an undamaged eye would carry out, and images are transmitted along the optic nerve. A subcutaneous silicone cable connected to the chip leads under the temporal muscle to a wireless power control unit under the skin behind the ear.

Retina Implant AG, a spin-off of the University of Tuebingen, was set up to further develop and commercialise the technology, receiving a grant from the German Federal Ministry of Research and Education towards its subretinal research in 2003. The aim of the company was to restore useful vision to the blind in order to provide these patients with some independence and to date clinical trials have produced positive results.

Retina Implant’s first human clinical trial began in 2005 at the University Eye Clinic of Tuebingen, Germany, with 11 patients. Results of this ground-breaking trial were published in the Proceedings of the Royal Society B³ last November. The study discussed the clinical results of the first trial which surpassed the company’s expectations. The implant was left in the eye for three months and patients received training in the optimal way to use the vision they obtained. Even without training, the participants were able to distinguish objects such as windows and cutlery.

Patient number 11, 46-year-old Miikka Terho from Finland, noticed the first symptoms of his condition in 1988 when he was just 24 years old. By the time he reached 30 years of age, he was completely blind.  In 2008, Miikka underwent a procedure to insert the implant transchorodially along a guiding foil into the subretinal space. Seven days later, Miikka began psychophysical testing starting with electrical stimulation to establish light detection.

In his first task, Miikka received single-electrode single-pulse stimulation (0.5-6ms pulses, typically 20-60 nC per electrode) that appeared as whitish round dots. Sample patterns were also presented by pulsing electrodes sequentially, the letter U for example. The second task involved the chip being operated at a rate of 1-20 Hz with a pulse duration of 1-4ms and a viewing distance of 60cm. This tested spatial resolution using grid patterns. After these early stages had been completed successfully, Miikka was tested using more naturalistic scenes, such as a dining table, words written in 8cm type, and foreign objects including an apple and a banana. After three months of testing the chip was explanted as a requisite of the trial.

A second trial using the company’s new wireless device was recently completed in Germany. Unlike the first human clinical trial, patients are able to keep the implant permanently and use the microchip in real-life settings. Nine patients were implanted and the results indicate the best visual acuity to-date, with the majority of participants experiencing restoration of useful vision in daily life. The vast majority of patients experienced visual perception indoors and outdoors in both dim and bright environments. Additionally, patients reported the ability to see objects 30 feet away and to read numbers on a pair of dice.

The scientific advisory board recently granted unanimous approval for the clinical trials to be expanded at three European centres in 2012, including the UK, based on the results of the first trial. In January, the John Radcliffe Hospital in Oxford and King’s College Hospital in London began trialling the technology for the first time in the UK, led by Robert MacLaren, professor of ophthalmology and Mr Tim Jackson, consultant retinal surgeon. Also factoring into the board’s decision to continue the trials is that the subretinal, surgical technique to implant the device continues to be safe and effective.

Professor MacLaren commented: “We are delighted to be involved in testing this pioneering subretinal implant technology. The results achieved by the Retina Implant team to-date represent a significant advance in this technology that could greatly enhance the quality of life for people with an incurable, blinding disease. We are looking forward to working with Retina Implant to build on this impressive body of evidence.” Dr Walter-G. Wrobel, president and CEO, Retina Implant AG, said: "Our team is encouraged by the results of this study and we look forward to continuing to build on the successes we have seen in the clinical trials by replicating this study in order to impact more lives. This study proves that the technology can work well while offering patients the mobility and the freedom to see beyond the laboratory setting. We look forward to presenting additional data in the future as more patients are implanted in Germany and beyond."

References

1. Moore, G.E., 1965, Cramming More Components onto Integrated Circuits, Electronics, Vol. 38, No. 8

2. Newling, D, 2006, Britons ‘could be microchipped like dogs by 2016’, Daily Mail Online

3. Zrenner, E. et. al, 2010, Subretinal electronic chips allow blind patients to recognise letters and combine them to words, Proceedings of The Royal Society B, 00, 1-9