These real-world applications might be the fruit of biomaterials sensing research conducted at the University of Houston Cullen College of Engineering by Peter Vekilov, associate professor of chemical engineering.

The ultimate goal of Vekilov’s research is to design a medical diagnostic system small enough to fit in a pill and capable of detecting the presence of almost a half million disease markers simultaneously.

Much of Vekilov’s work builds on the efforts of researchers across the world tasked with cataloging the attributes of some 400,000 proteins, many of which are specific to diseases, or antibody proteins generated in response to disease pathogens: viruses, bacteria, etc. These antibodies are created by the human immune system to fight disease and each bonds only with a single matching protein that is characteristic to the disease.

Researchers expect to utilize their increasing knowledge of protein/antibody relationships to diagnose illnesses. Simply put, the goal is for medical professionals to expose biological material to a protein antibody. Since each protein antibody can only bond with a specific disease protein, medical personnel can be sure a disease is present if a bond forms.

According to Vekilov, proteins are getting more attention from the scientific community since recent efforts in genome mapping show that humans have only 22,000 genes—far too few to account for everything that happens in organisms as complex as humans.

“The new theory, then, is that processes in organisms are governed by the variability of the 400,000 proteins in them,” he said. “Hence the need to detect, identify, analyze, catalogue and diagnose the proteins in a human tissue or organ.”

Vekilov’s goal is to create an easily mass-producible tool that relies on the formation of protein/antibody bonds to diagnose hundreds of thousands of diseases. The description of such a tool provides a clear picture of how nanotechnology devices are built, as well as some of the challenges that can be inherent in building them.

Specifically, Vekilov’s diagnostic tool can be produced easily with available semiconductor technologies. Silicon wafers measuring 30 cm in diameter will be divided into up to 70,000 separate sections measuring one square milli-meter each. On each section, researchers will place arrays of 100,000 to 500,000 electrodes.

Before the arrays are physically separated, the first electrode on each will be charged with a single volt of electricity and then bathed in a nanodroplet of a solution of an antibody sensitive to a specific protein. The volume of these solutions is incredibly small, measuring 10-16 liters, about 100 attoliters. The charge on the electrodes will allow them to bond with the solution, after which the solution will be rinsed from the arrays. The process will then be repeated hundreds of thousands of times using a different antibody each time.

When an array is exposed to biological material, the antibodies on the electrodes will detect the presence of their matching proteins and an electric signal will be generated and transmitted by additional electronics.

While this general approach has been proven viable, says Vekilov, the real challenge is in making it practical. Dividing a silicon wafer into such small sections isn’t the problem; depositing hundreds of thousands of different protein solutions on a single wafer in a cost- and labor-efficient manner is where the challenge comes in. “We recently developed a procedure to deposit such attoliter droplets of a protein on sub-micron sized electrodes.”

However, with this recently developed procedure, researchers must customize the conditions of the liquid solution in which the antibody proteins will be mixed in order to deposit them successfully. Different proteins require their solutions to have a specific temperature or acidity level, for example.

Determining the precise solution properties for each protein would require years of research and millions of dollars. And even if the exact solution for each protein were formulated, using hundreds of thousands of solutions to mass produce arrays would be practically impossible.

“We want to avoid that,” says Vekilov. “We have to develop a general procedure where even if you know nothing about the protein, you’ll still be able to deposit it.”

This problem, Vekilov says, can be overcome by creating a universal solution that can be used in conjunction with any protein.

Vekilov theorizes that this can be accomplished by creating a single solution that masks proteins’ attributes that require specific solution properties. A search for suitable agents is underway.

If this theory proves correct, every protein could be mixed with a single solution. This one solution would result in the development and mass production of this diagnostic tool becoming much simpler and more cost-efficient.

“The practical result is that even without knowing anything about a protein you’ll be able to deposit it. You won’t have to study it, you won’t have to use different conditions,” Vekilov says.

Once Vekilov devises a solution to mass-produce arrays efficiently, the next question becomes how to deliver them.

There are several possible ways to accomplish this, Vekilov says, each of which could be used for different purposes. For example, an array, which measures just one square millimeter, could be placed in a pill-sized capsule, which by practice measures up to nine square millimeters. The remaining space could be used to house data recording and transmission equipment. A patient would then simply swallow the capsule, which would radio out information to a medical professional about any protein/antibody bonds that form.

Alternatively, individuals could have an array embedded underneath their skin that would constantly monitor for the presence of protein/antibody bonds and, in any number of ways, alert the individual should a bond be detected.

These different delivery methods demonstrate the advantages of such a diagnostic system. In pill form, patients experiencing symptoms of an unknown disease or condition can be diagnosed in minutes. An array embedded underneath the skin could serve as an early detection device, alerting at-risk individuals that a disease is present long before symptoms appear.

Will people be able to discover and fight illnesses before their effects are even felt? Is a “smart” pill capable of diagnosing practically any disease in minutes in the near future? Vekilov believes so and is developing tools that will make these seemingly futuristic technologies a reality.

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