A Serum-to-Smartphone Biochip for Detecting MI

Editor's Note: This was originally published in the May, 2013 issue of CardioSource World News in the Column “Health Tech” authored by Shiv Gaglani. Reprinted with permission.

Many of the devices covered in this column rely on electrical activity to assess heart function. These range from the AliveCor smartphone case with built-in one-lead ECG to MC10's flexible electronics that can be attached to the heart's surface. While electrical activity can obviously tell us much about the heart's status, there are other important biological and chemical signals that an increasing number of devices are now drawing from to make diagnoses. One of the most impressive is an implantable, 14-mm-long biochip that continuously monitors the blood for small molecules, while also transmitting these data to a smartphone via Bluetooth. So, for example, it can detect a spike in cardiac troponin and alert the patient that they may be having an MI. I spoke with one of the device's inventors, Professor Sandro Carrara of the École Polytechnique Fédérale de Lausanne in Switzerland, about this technology and how it may be applied in cardiology.

Can you walk us through the various components of your biochip—e.g., sensors, power source, data transmission, and processing on the phone?

In theory, a patient will go to a health care provider where the chip will be inserted via syringe. A "smart patch" will be placed on the skin over the implant and will be responsible for receiving the data and transmitting them to the patient's smartphone. In its current form, the chip itself comprises seven sensors: five that detect molecules, one for temperature, and one for pH. It also contains the integrated circuit required for receiving and managing power and the front end for driving and reading the sensors. The multifold antenna receives power from the patch and transmits acquired data back to the patch. The patch comprises an inductive coil, a Bluetooth system, and two lithium batteries. The smartphone receives and processes the raw data to reflect the blood levels of various important metabolites, such as glucose, cholesterol, lactate, etc.

What are the limiting factor(s) that prevent the biochip from being used continuously for more than 1–2 months at a time?

The main limiting factor is the stability of the enzymes we are using to sense the metabolites. For example, we used the natural enzyme glucose oxidase to measure glucose levels, but that protein only survives up to 34 days in our experiments. However, others have already shown glucose sensors surviving for more than one year in porcine trials. The longest-lasting sensor in our trial operated for more than 40 days and relied on an engineered enzyme that sensed lactate. On the other hand, the shortest-lasting sensors are those for drugs because they require the ephemeral cythochrome P450 enzyme. Fortunately, drug monitoring is usually only required for pharmacokinetic studies over the frame of hours and not months, and there are promising new engineered proteins and surface immobilization techniques that may prolong the lifetime of our drug sensors.

How can this be used in the field of cardiology?

In general, the sensor may be helpful to patients due its ability to sense glucose and cholesterol, both of which play key roles in cardiovascular health. In addition, we have been able to monitor metabolites like troponin, which opens the door for monitoring patients who are at risk for heart attack and cardiovascular damage.
Those focused on health care cost control may ask why we need to have an implantable biochip—how would you respond?
The symptoms of a myocardial infarction can be nonspecific, such as palpitations, diaphoresis, or chest pain. This can lead to false positives in which the patient goes to the hospital, contributing to the rise in health care costs, even though they only had a bit of arrhythmia. Conversely, sometimes ischemia can occur without associated chest pain and thus relying on symptoms alone would lead to a false negative result.

Our chip would be able to directly monitor troponin levels in the blood of the patient and compare its value over time. If the troponin concentration is constantly increasing over the course of an hour, this likely represents myocardial damage and the chip would be able to notify the patient to seek medical attention immediately. The international community already has shown that this kind of monitoring can predict heart attacks up to four hours earlier, which has great potential to save lives!

What are your next steps to moving this from the bench to the bedside?

We are forming joint research projects with companies interested in specific applications, such as monitoring patients in intensive care units or under general anesthesia during surgery. Successful application of the chip in these cases can bring us closer to the goal of continuous ambulatory monitoring.
How did you become involved in this field?

I am a physicist with a PhD in biochemistry and biophysics. I have worked in the area of biosensors over the last 20 years. My medical colleagues, including pharmacologists and physicians, presented me with several cases whereby the use of biosensors would have helped with early stage response and treatment. Finally, a few years ago we developed the idea to integrate several biosensors into an implantable chip to broaden the diagnostic spectrum.

What are you most excited about in terms of medical technology over the next five years? 20 years?

In the next five years, we will have several (maybe many!) apps for our smartphones and tablets that will provide us point-of-care personalized diagnostics. In the next 20 years, some humans will be fully connected to the Internet via wearable and implantable sensors that provide real-time, continuous monitoring and medical surveillance.

Shiv Gaglani is an MD/MBA candidate at the Johns Hopkins School of Medicine and Harvard Business School. He writes about trends in medicine and technology and has had work published in Medgadget, The Atlantic, and Emergency Physicians Monthly.

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