Nanomedicine Portal

Demir Akin, DVM, PhD
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Nanomedicine | BioMEMS/NEMS Biosensors/Biomolecule Capture and Sorting | Single Molecule Imaging | Virology | In Silico Biology

Microbotics: Bacteria-mediated delivery of smart nanocargo into cells

Akin, D., J. Sturgis, K. Ragheb, D. Sherman, K. Burkholder, J. P. Robinson,  A. K. Bhunia, S. Mohammed and R. Bashir.  Bacteria-mediated delivery of nanoparticles and cargo into cancer cells. Nature Nanotechnology, 2:441-449, 2007.  (download PDF)

Nanoparticles and bacteria have been independently used to deliver genes and proteins into mammalian cells for monitoring or altering gene expression and protein production. Here, we show the simultaneous use of nanoparticles and bacteria to deliver nucleic acid-based model drug molecules into cells and mice. In our approach, the gene or cargo is loaded onto the nanoparticles, which are carried on the bacteria surface. The bacteria successfully delivered the molecules, and the genes were released from the nanoparticles and expressed in four different cell types and mice. This new approach may be used to deliver different types of cargo into a variety of cells and live animals without the need for complicated genetic manipulations.

Bioinspired-Cancer Drug Delivery "Cellular Trojan Horses" 

Choi, M.R., Stanton-Maxey, K.J., Stanley, J.K., Levin, C.S., Bardhan, R., Akin, D., Badve, S., Sturgis, J., Robinson, J.P., Bashir, R., Halas, N.J., Clare, S.E.  A Cellular Trojan Horse for Delivery of Therapeutic Nanoparticles into Tumors. Nano Letters, In Press, 10.1021/nl072209h S1530-6984(07)02209-6, 2007.

Destruction of hypoxic regions within tumors, virtually inaccessible to cancer therapies, may well prevent malignant progression. The tumor's recruitment of monocytes into these regions may be exploited for nanoparticle-based delivery. Monocytes containing therapeutic nanoparticles could serve as "Trojan Horses" for nanoparticle transport into these tumor regions. Here we report the demonstration of several key steps toward this therapeutic strategy: phagocytosis of Au nanoshells, and photoinduced cell death of monocytes/macrophages as isolates and within tumor spheroids.
cancer drug delivery via Trojan Horses

Solid-state Nanopore Channels with DNA Selectivity

Iqbal, S.,D. Akin and R. Bashir. Solid State Nanopores with DNA Selectivity. Nature Nanotechnology, 2:243-248, 2007.  (download PDF)

Solid-state nanopores have emerged as possible candidates for next-generation DNA sequencing devices. In such a device, the DNA sequence would be determined by measuring how the forces on the DNA molecules, and also the ion currents through the nanopore, change as the molecules pass through the nanopore. Unlike their biological counterparts, solid-state nanopores have the advantage that they can withstand a wide range of analyte solutions and environments. Here we report solid-state nanopore channels that are selective towards single strand DNA (ssDNA). Nanopores functionalized with a 'probe' of hair-pin loop DNA can, under an applied electrical field, selectively transport short lengths of 'target' ssDNA that are complementary to the probe. Even a single base mismatch between the probe and the target results in longer translocation pulses and a significantly reduced number of translocation events. Our single molecule measurements allow us to separately measure the molecular flux and the pulse duration, providing a tool to gain fundamental insight into the channel-molecule interactions. The results can be explained in the conceptual framework of diffusive molecular transport with particle-channel interactions.
nanopore with DNA

Biomedically Relevant Nanomaterials and their Biocompatibility 

Bajaj, P.,D. Akin, A. Gupta, O. Auciello and R.Bashir.  Ultrananocrystalline diamond film as an optimal cell interface for biomedical applications.Biomedical Microdevices, I9:787-94, 2007.

Surfaces of materials that promote cell adhesion, proliferation, and growth are critical for new generation of implantable biomedical devices. These films should be able to coat complex geometrical shapes very conformally, with smooth surfaces to produce hermetic bioinert protective coatings, or to provide surfaces for cell grafting through appropriate functionalization. Upon performing a survey of desirable properties such as chemical inertness, low friction coefficient, high wear resistance, and a high Young’s modulus, diamond films emerge as very attractive candidates for coatings for biomedical devices. A promising novel material is ultrananocrystalline diamond (UNCDŽ) in thin film form, since UNCD possesses the desirable properties of diamond and can be deposited as a very smooth, conformal coating using chemical vapor deposition. In this paper, we compared cell adhesion, proliferation, and growth on UNCD films, silicon, and platinum films substrates using different cell lines. Our results showed that UNCD films exhibited superior characteristics including cell number, total cell area, and cell spreading. The results could be attributed to the nanostructured nature or a combination of nanostructure/surface chemistry of UNCD, which provides a high surface energy, hence promoting adhesion between the receptors on the cell surface and the UNCD films.

Micro/Nanoscale cantilevers as biosensors

Gupta, A., P.R. Nair,D. Akin, M, Ladisch, S. Broyles, M. A. Alam and R. Bashir.  Anomalous resonance in a nanomechanical bioSensor. Proc. Natl. Acad. Sci., USA, 103:13362-13367, 2006.

Normally a cantilever's resonant frequency decreases when molecules attach to it – a finding that is the basis of nanomechanical sensing devices- but we have found that the resonant frequency of some nanoscale cantilevers may actually increase on the addition of molecules.  Area-dependent protein adsorption is shown in the side figure. (a) Schematic diagram depicting the methodology of the specific binding of the secondary Abs to the proteins used in scheme 1. (b) Photomicrograph of fluorescently labeled (FITC; green) Ab to BSA attached to varying sized cantilever beams clearly showing an increase in fluorescent intensity for longer cantilevers. (Scale bar, 5 μm.) (c) Semilog plot showing the measured average fluorescence intensity from the secondary Abs to the proteins used in scheme 1 as a function of cantilever beam area. (Inset) The same parameters in the linear scale. The squares indicate the simulated protein density at the tip of the cantilevers shown in b. The simulated value of the shortest cantilever beam (LC = 5 μm in b) was normalized with the measured value of the same length scale, the remaining two simulated lengths (LC = 10 and 15 μm) were scaled by the same factor, and then all three simulated values were plotted with the measured data. (d) Simulated protein density distribution on the adsorbing cantilever surfaces. The density reaches a maximum for the longer cantilever. The monotonic increase in density with the cantilever length is due to the competitive attachment of protein among the adsorbing surfaces. Simulated protein density at the tip of the cantilevers is in excellent agreement with the experimental results.


Biohybrid Nanodevices for Nanomedicine

Use of Bacteriophage Phi-29 Packaging RNA NanoMotor for Active Devices for Nanomedicine:

Demir Akin, Peixuan Guo, Chengde Mao, and Rashid Bashir,

A specific project funded through NIH Nanomedicine Center involves the use of the Phi-29 packagaing RNA nanomotor and interfacing this biological motor with micro/nano fabricated devices. The center overview can be found at ( The goal of the proposed Nanomedicine Development Center (NDC): “Phi29 DNA-Packaging Motor for Nanomedicine”, is to create biologically compatible membranes and arrays with embedded and active phi29 DNA-packaging motors for applications in medicine. For example, currently there is no nanodevice available for actively pumping drugs, DNA/RNA and other therapeutic molecules into specifically targeted cells. Our NDC, (also referred to as the Nanomotor Drug Development Center, NDDC), will create a hybrid system that combines the best features of the biological motor with synthetic delivery systems that have already achieved clinical success. The re-engineered motors developed will also be applied in various array formats to extend application to diagnostics and other therapeutic approaches. One of the thrusts is to develop novel diagnostic and therapeutic devices by integrating the phi-29 motor to micro/nano fabricated surfaces. We are working on making arrays of these motors for possible application selective filteration and sieving devices. Specifically we are working on use of surface fucntionalization techniques to form motor arrays on silicon surfaces and demonstrate the operation of motor arrays. Next we will work on use of nanoporous membranes and attempt to attach the nanomotors on these membranes in hopes to make selective sieving and filteration devices.

Nanoscale cantilevers:

Normally a cantilever's resonant frequency decreases when molecules attach to it – a finding that is the basis of nanomechanical sensing devices- but we have found that the resonant frequency of some nanoscale cantilevers may actually increase on the addition of molecules.

Shown here is an array of functionalized cantilvers. An array of tiny, diving-boardlike devices called nanocantilevers. The devices are coated with antibodies to capture viruses, which are represented as red spheres. New findings about the behaviour of the cantilevers could be crucial in designing a new class of ultra-small sensors for detecting viruses, bacteria and other pathogens. (Image generated by Seyet, LLC).

A. Gupta, P. Nair, D. Akin, S. Broyles, M. Ladisch, A. Alam, R. Bashir, "Anamolous Resonance in a Nanomechanical Biosensor", Proceedings of National Academy of Sciences, USA. August 28, 2006, 10.1073/pnas.0602022103 - (download PDF)


Cell mass sensing and measurement of growth changes:

Park, K., J.Jang,D. Akin, D. Irimia, M. Toner, and R. Bashir. Capture, growth and mass measurement of mammalian cells on silicon cantilever arrays. Biomedical Engineering Society, September 22, 2007, Los Angeles, LA.

cell mass

Tissue Engineering and Biohybrid Devices

Our improved understanding of how biological systems, from proteins to subcellular compartments to cells, to tissues, to organs, and eventually, to the entire organism are formed and regulated, and the nanoscale control of sythetic material physicocehmical properties will enable us to devise and realize the next generation of nanomedical systems for improvement of human health. Towards these goals, we adopt the emerging cutting edge biomedical research findings into engineering and perform research and developement in biohybrid devices. One example of these is given in the figure in the right column. A microfabricated cantilver is surface functionalized and embryonic cardiomyocytes are grown on it, forming a beating sheet of cardiac tissue that actuates the cantilever. These types of devices have desirable properties for numerous areas of bioinspired and engineered biomedical solutions, from drug screening to bidirectional signal conversion between biological and electronic signals, bioenergy to drug delivery, to artificial organs.