Nanotechnology The Merging of Diagnostics and Treatment

Abraham Phillip Lee, University of California at Irvine

The key to advancing from the discovery stage of nanoscience to commercially feasible nanotechnology is the ability to reliably manufacture nanoscale features and control nanoscale functions. The application of nanotechnology towards biology further requires the functional nano-interface between artificial and biological components. From a systems perspective, this requires signal transduction at matching impedances so that sensitivity and specificity are adequate to decipher the biological events. The maturation of these capabilities will enable the probing and manipulating of the fundamental building blocks of biology, namely biomolecules such as carbohydrates, lipids, nucleic acids, and proteins.

The biological cell has proven to be the most intricate functional system of its scale. Unique functionalities include its ability to regulate and adapt, hierarchical self-assembly, repair and maintainance, parallel processing, just-in-time processes, asynchronous control and signaling, and scalability from nano to macro. However, these features and functions are hard to quantify, model, engineer, and reprogram. On the other hand, microfabrication and nanofabrication techniques have given us integrated nanoscale electronics, microfluidics, microelectromechanical systems (MEMS), and microphotonics. These top-down fabrication techniques allow addressability of large-scale component platforms. On the other hand, bottom-up nanofabrication techniques (such as self-assembly) mimic how biology builds very complex systems out of simple molecules. As the scale of these two fields overlaps, devices can be developed with high sensitivity and selectivity for detecting and interfacing to biomolecules.

Projects exemplifying the field of nanobiotechnology include single molecule detection studies, functional imaging of cells and biomolecules by scanning probe microscopy, nanoparticles for targeted therapy, nanomechnical devices to measure biomolecular force interactions, etc. These research efforts represent the start towards interfacing with biological functions at the most fundamental level. However, biology is the intertwined combination of many single molecular events, each being coupled with one another either synchronously or asynchronously. To truly unveil biological events such as cell signaling pathways, genetic mutation processes, or the immune responses to pathogens, one must have a method to generate large-scale, multifunctional nano-bio interfaces with readout and control at the single biomolecule level.

I provide three visions for features of the nanobiotechnology roadmap:

1. The development of a "biological microprocessor" for synthesizing and analyzing biomolecules on nano platforms (liposomes, nanoparticles, self-assembled monolayers, and membranes) in fluids. These "biomolecular nanotransducers" will be able to function (1) as multiplexed nanomedicines capable of long duration, in vivo targeted detection, diagnosis, and treatment of molecular diseases; (2) as key ingredients of smart coatings for versatile environmental monitoring of toxins/pathogens; and (3) as engineered biomolecular nanosystems that mimic cellular functions for fundamental biology experiments.

2. The coupling of biomolecular units — whether they be DNA, receptors, antibodies, or enzymes — with MEMS for reassembly of cell components and reprogrammed cell functions. This will enable the rewiring of biological cell pathways in artificially controlled platforms such that it will be possible to carry out preclinical experiments without the use of animals or humans.

3. The coupling of "nano guards for health" (e.g., nanoparticles) with microfluidic controllers for long-term control of certain health parameters. For instance, the feedback loop of a glucose sensor and delivery of nano artificial islets can enable the merging of detection, diagnosis, and treatment into one MEMS device.

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