Guinevere Strack

Biocomputing Security System: Concatenated Enzyme-Based Logic Gates Operating as a Biomolecular Keypad Lock

A biomolecular security system mimicking a keypad lock device was developed using enzyme-based concatenated AND logic gates resulting in the implication logic network.

Boolean logic gates that use enzymes as input signals.

Biochemical systems that demonstrate the Boolean logic operations AND, OR, XOR, and InhibA were developed by using soluble compounds, which represent the chemical “devices”, and the enzymes glucose oxidase (GOx), glucose dehydrogenase (GDH), alcohol dehydrogenase (AlcDH), and microperoxidase‐11 (MP‐11), which operated as the input signals that activated the logic gates. The enzymes were used as soluble materials and as immobilized biocatalysts. The studied systems are proposed to be a step towards the construction of “smart” signal‐responsive materials with built‐in Boolean logic.

Enzymatic AND Logic Gates Operated Under Conditions Characteristic of Biomedical Applications

Experimental and theoretical analyses of the lactate dehydrogenase and glutathione reductase based enzymatic AND logic gates in which the enzymes and their substrates serve as logic inputs are performed. These two systems are examples of the novel, previously unexplored class of biochemical logic gates that illustrate potential biomedical applications of biochemical logic. They are characterized by input concentrations at logic 0 and 1 states corresponding to normal and pathophysiological conditions. Our analysis shows that the logic gates under investigation have similar noise characteristics. Both significantly amplify random noise present in inputs; however, we establish that for realistic widths of the input noise distributions, it is still possible to differentiate between the logic 0 and 1 states of the output. This indicates that reliable detection of pathophysiological conditions is indeed possible with such enzyme logic systems.

Biofuel Cell Logically Controlled by Antigen-Antibody Recognition: Towards Immune-Regulated Bioelectronic Devices

A switchable biofuel cell logically controlled by immune signals was developed as a model prototype for future adaptive implantable bioelectronic devices regulated by immune reactions. The cell demonstrated NOR Boolean logic operation in situ controlled by antibody signals.

Logic Networks Based on Immunorecognition Processes

The biochemical system logically processing biochemical signals using immune-specific and biocatalytic reactions was designed, and the generated output signals were analyzed by AFM and optical means. Different patterns of immune signals resulted in the formation of various interfacial structures followed by biocatalytic reactions activated by the next set of biochemical inputs. The developed approach to multisignal biosensing allows qualitative evaluation of the biochemical information in terms of YES-NO, providing the base for novel molecular-level logic analysis of complex patterns of biochemical signals. Application of AFM to read out the structures generated on the interface could potentially lead to substantial miniaturization of the immune logic systems.

Atomic force microscopy study of immunosensor surface to scale down the size of ELISA-type sensors

Here we describe the use of atomic force microscopy (AFM) to study the nanoscale mechanics of the molecular layers of a popular immunosensor, ELISA (enzyme-linked immunosorbent assay) type. We characterize the sensor surface in terms of brush length and grafting density of the molecular layers. The obtained data demonstrated that a reliable reading of the immunosignal (a suggested dimensionless combination of brush length and grafting density) can be attained from an area as small as approximately 3 microm(2). This is approximately 4 million times smaller compared to typical ELISA sensors. The immunosensor described is composed of a molecular mix of two different antigens. Intriguingly, we find that AFM can reliably distinguish between having the immunosignal from either antibody and from both antibodies together. This was impossible to get by using standard optical detection methods.

Alert-type biological dosimeter based on enzyme logic system

A cooperative effect of two biomarkers, α-amylase and lactate dehydrogenase, was used to analyze radiation-caused tissue damage in vitro in model solutions of human serum. The analytical system was based on the recently emerged biocomputing concept applying biocatalytic cascades for logic processing of biochemical input signals. The studied system resembled a Boolean NAND logic gate in which the change of the optical output signal from a high level (logic value 1) to a low level (logic value 0) confirmed the presence of both biomarkers at pathological concentrations (1,1 input signals), thus yielding the conclusion about radiation tissue damage. The system operates in a digital YES/NO format as an alert-type biosensor with a built-in Boolean logic.