Biosensors Boost Biomedical Advancement

Mathematicians first introduced the concepts of logic gates and Boolean algebra in the 18th century. Today, we think of Boolean logic as the binary number system used to design electronic circuits and computing systems.

Evgeny Katz, however, has a different idea. He wants to build a computer using biomolecules in living cells.

“Sometimes the best ideas come from the most unexpected places,” says Katz. His came about 15 years ago when he was an editor for a book on bioelectronics, a field that uses biological materials and architecture to design information processing systems and devices. He came across research on DNA computing, which uses DNA-based materials to design computing technologies.

That got Katz thinking about his own research on enzymes, proteins that catalyze biochemical reactions. He wanted to design enzyme-catalyzed reaction cascades that mimic Boolean logic.

These reaction cascades would act as pathways that transmit signals, in the same way that tiny electrical circuits in electronic devices do.

Sometimes the best ideas come from the most unexpected places.

Enzyme-based Biocomputing

Evgeny Katz in his lab
Dr. Evgeny Katz

Katz’s pioneering idea addresses the need for novel approaches in information processing. Conventional computing technologies using silicon-based materials have passed their prime because of limitations in the continued miniaturization of computer components and processing speeds. In biocomputing, scientists design biological reactions based on the input for the desired system. Possibilities for output signals include specific biochemical products, mechanical shapes of specific molecules and electrical conductivity. These signals can subsequently be analyzed computationally.

The building blocks for Katz’s biocomputer are a series of enzymatic reactions. “The challenge lies in stacking these individual reactions into a cascade that will give you the desired output,” Katz explains. The aim is to arrange these reactions into Boolean logic networks that can process multiple biochemical signals and produce a YES/NO output.

Katz’s group has already successfully demonstrated practical applications for enzyme-based biocomputing.

One example is the biofuel cell that uses living organisms to generate electricity. It comprises two electrodes that catalyze the oxidation of glucose and the reduction of oxygen. When both reactions are running, one can extract electrical power from the current generated by the system. “It’s not very different from regular fuel cells, except that we are using biological catalysts and biological fuels,” Katz says.

His team is the first to successfully implant a biofuel cell in a live snail. They have since shown that the system is also operational in clams and lobsters. Since oxygen and glucose are readily available and can be replenished under normal physiological conditions, these “electrified” creatures can produce sustainable electricity to power various microdevices.

“Sense-and-Act” Systems

Katz’s lab has also been researching implantable multi-input biosensors with built-in logic to determine how they can be used as methods of targeted drug release.

The system uses two electrodes that are connected electrically. One is a sensor for biomarkers that indicate an injury or a change in a particular condition, while the other is a signal-responsive electrode coated with a reactive polymer film that traps the medicine. When the specific biomarker is detected, the system initiates an oxidative reaction that produces a current that causes the polymer film to dissolve, and the medicine is released. For instance, in the case of patients with diabetes, high blood glucose levels would trigger the release of insulin.

“This ‘sense-and-act’ system is analogous to connecting a printer to a computer; the computer processes the information and the printer generates the output,” Katz explains. The coenzyme (nicotinamide adenine dinucleotide, or NADH) that Katz and his team are using to trigger the substance release is readily available in living organisms.

Recently, Katz, his Clarkson colleague Vladimir Privman and collaborators from the University of Missouri won a competitive National Science Foundation grant to develop this system into one that can analyze various combinations of signals and biomarkers, particularly for biomedical applications.

Katz’s latest research involves finding a way to identify cancerous cells. He is using DNA-based enzymes to detect a gene that promotes metastasis in breast cancer cells. This system can quickly process biological information inside the cell, and the results can be read on a computer.

Besides medicine, Katz hopes to apply his technology to environmental monitoring and homeland security, such as in detecting weapons on the battlefield.

“The potential application of this system is widespread,” he says. “I want to continue developing new concepts and possibilities.”