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As of June, 2005
More information about these technologies, as well as a list of publications, can be found at: http://chem-faculty.ucsd.edu/sailor/research/
This technology platform has applications in:
- High- and low-throughput screening
- Filtration
- Sample concentration
- Chemical and Biological sensing
- Remote/low power sensing
- Encoding/Barcodes
- In-vivo diagnostics
- In-vivo therapeutics
- Self-assembly, targeting
- CRT and other displays
- Communications products
Technologies, listed by case number:
SD1991-271
Photolithographic Fabrication of Luminescent Images on Porous Silicon Structures [US Pat. 5,318,676 ]
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SD1991-272
Method for Detection of Chemicals by Reversible Quenching of Silicon Photoluminescence [US Pat. 5,338,415 ]
An n-type silicon wafer is processed to form a porous silicon surface with luminescence properties. Photoluminescence of the porous Si is monitored using short wavelength visible light or an ultraviolet source and a monochromator /CCD detector assembly.
Upon exposure to organic solvents, the photoluminescence is quenched. Within seconds of removal of the solvent, the original intensity is recovered and further exposure of the porous Si to organic solvents will again result in quenching of the luminescence
The sensitivity of the method suggests its application as a chemical environmental sensor.
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SD1997-064
Device for Detection of Organic Compounds, Ions and Other Molecular Species by Optical Interference in a Porous Silicon Layer [US Pat. 6,248,539 , 6,720,177 and 6,897,965 ; more pending]
Background: Combinatorial chemistry is arguably the most important development in the drug discovery process in over a decade. However, the detection of significant biological events in high throughput screening involves many burdensome tasks, and often includes the separation of the products of reaction before detection can take place.
Description: This chemistry provides a means to sensitively measure the quantity of a chemical compound or element of interest (analyte) by measuring the effect it has on the optical interference spectrum from a layer of porous silicon that may or may not have been modified to enhance the binding of the analyte.
Advantages: This invention has excellent applications to homogeneous assay systems because organic compounds can be detected in solutions without separating them, removing the burdensome step of washing out the compounds. This method may be performed using nanoliters of reactants.
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SD1999-106
Thin-film Optical Sensor for Gas and Liquid Detection [Pat. pending]
Porous silicon layers prepared to show fine structure in the reflection spectra provide the means to measure the composition of a gas or liquid. Adsorption of molecules in the pores changes the average refractive index of the thin-film which produces a variation in the Fabry-Perot interference fringes. These spectral changes can then be correlated to the pressure of a gas in contact with the sensor.
It has now been shown that there is a time-dependant response of the thin-film to a pulse of pressure and this response is observable in the shift of the Fabry-Perot fringes. The effects are reversible, and the sensor may be used either in a continuous reflectivity configuration to measure the pressure of a gas, or in a time-resolved reflectivity configuration to give the composition of a mixture of different gases. In this later mode it is the equivalent of a chromatographic experiment, with the distinction being that the separation medium is also the sensor.
- Reversible detection system.
- Easy and cheap to produce via etching or oxidative processing of silicon wafers.
- Can be used in either continuous mode to measure gas pressure or in time-resolved mode to provide real-time determination of gas compositions.
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SD2001-054
Nanoporous Silicon Bioreactor [US Pat. 6,734,000 ; more pending]
UCSD researchers have developed a silicon-based bioreactor. Initial studies have been done with primary hepatocytes from rat, stabilized in cell-sized pores of porous silicon. Physiological and biochemical activities of the cells were quantitatively evaluated over time. The hepatocytes adhered to the silicon and maintained viability similar to controls. Silicon-based cells also maintained liver specific functions, including urea synthesis and albumin secretion. This novel, silicon micro-bioreactor serves a dual role, stabilizing the cellular phenotype and facilitating efficient mass transfer between the fluid and the cells. This invention has applications for further development in many areas, from tissue engineering to drug discovery applications.
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SD2002-075
Optically Encoded Nanoparticles [Pat. pending]
Researchers at the University of California at San Diego have invented an optical encoding method for encoding micron-sized nanoporous semiconductor, conductor, or dielectric particles to be used in biological and/or chemical screening, sensing, or identification application. Particles are optically encoded by changing process conditions during porosification. The particles can thereby be chemically modified for specific biological, biomedical, electronic, or environmental applications. The method, employing reflection spectroscopy, does not have the disadvantage of photobleaching inherent with fluorophores. Additionally, fluorescent analytes do not interfere with the particle signal.
Moreover, the method is biocompatable, and can be applied to the screening of large numbers of analytes in vivo.
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SD2002-124
Explosive Nanocrystalline Porous Silicon Device [Pat. pending]
Researchers at the University of California, San Diego, have developed a solid state device fabricated from a high surface area porous silicon substrate and nitrate salts. On ignition, the material produces a very clean burning flame. Although ignition can be initiated by a low voltage source, the device is stable at temperatures above 100 deg. C. Fabrication of this explosive “chip” is compatible with conventional silicon fabrication techniques.
Possible applications include a portable flame emission spectrometer for field use in metals contamination analysis; as a self-destruct mechanism for microelectronic devices, and as a safer, less shock-sensitive, programmable igniter for explosives. Another, use of this miniature silicon explosive might be as a propulsion source for micro-electrical mechanical systems, micro-robots or micro-satellites.
More details on the invention have been published in “Advanced Materials” volume 14, No.1, January 2002.
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SD 2002-144
Direct Patterning of Silicon by Photoelectrochemical Etching [Pat. pending]
Researchers at the University of California , San Diego , have invented a resistless projection lithographic method for generating three-dimensional patterns on silicon substrates. A porous silicon layer is first formed by projecting an image or test pattern onto a silicon substrate during standard electrochemical etching. The porous layer is then removed in a wet etch revealing a 3-D image or test pattern in micrometer resolution. This technique does not involve the use of complicated, multi-step lithography or mask aligners. It is also very quick; a multilayered master can be made from a computer design in less than 60 minutes. Feature sizes of 70 microns have been demonstrated, but smaller features should be possible.
A wide variety of fields, such as sensors, microfluidics, microanalysis, MEMS, and cell biology might benefit from this invention.
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SD2003-024
Nanostructured Casting of Organic and Biopolymers in Porous Silicon Templates [Pat. pending]
Synthesis of materials inside templates has emerged as a useful and versatile technique to generate three-dimensional nanostructures. Previous approaches use templates consisting of microporous membranes, zeolites, and crystalline colloidal arrays. These have been used to construct elaborate electronic, mechanical, or optical structures. Porous Si is an attractive candidate as a template because the porosity and average pore size can be readily tuned by adjustment of the electrochemical preparation conditions. Additionally, elaborate 2- and 2.5-dimentional photonic crystals are readily prepared in porous Si.
Researchers at the University of California , San Diego have demonstrated the templating of solution-cast and injection molded thermoplastic organic, inorganic, and biopolymers in porous Si multilayer (Rugate, Bragg filter) structures. The castings retain the photonic structure of the template. Demonstrated uses of the castings include vapor sensors, deformable and tunable optical filters, as well as self-reporting, bioresorbable drug delivery materials.
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SD2003-122
Chemically Modified Porous Si Films for Biosensor Applications [Pat. pending]
Researchers at the University of California , San Diego , have developed diffuse reflectance and microscopic FTIR techniques for characterization of modified porous Si (PSi) films, and to develop chemistry to stabilize PSi in aqueous buffered saline as well as providing attachment of biological molecules. In the course of this work, a novel method to markedly increase the stability of PSi films was discovered. The films show increased stability in aqueous media and increased resistance to mechanical stress, in comparison to thermally hydrosilated PSi films. These films were found to still retain photoluminescent properties and their physical-adsorption properties.
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SD2003-182
Determination of Protein Size [Pat. pending]
This invention teaches the preparation and use of porous Si films containing a controlled distribution of pore sizes for a unique bio-sensing application. Use of this invention to achieve the simultaneous separation and detection of a protein in a nano-machined silicon matrix is described. Gating of the response by adjustment of pH below and above the isoelectric point of the protein has also been demonstrated, and provides an additional means of bio-molecule separation and identification. This invention is useful for the determination of protein size and for the detection of weakly-bound complexes. In addition, the invention can controllably trap and release proteins from a microporous matrix and is useful for drug delivery applications, as porous Si has been shown to be bio-compatible and readily bio-resorbable.
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SD2003-214
Complex Optical Encoding of Porous Silicon Photonic Crystals [Pat. pending]
Researchers at the University of California , San Diego , have invented a method of optically encoding porous silicon photonic crystals for use in high throughput screening and bioassays. The method allows for large libraries of unique particle types to be manufactured.
The process is distinct from existing methods of encoding, such as fluorescent molecules, core-shell quantum dots, and photonic crystals formed using Rugate or Bragg reflectivity approaches, in that it does not strive to create spectral lines that act as bits-and are limited by the number of codes that can be generated. In contrast, this invention for data extraction and analysis utilizes all the complexity of the spectrum which results from the reflectivity properties of the photonic crystals. Unlike bioassay systems, which couple fluorescent encoding methods with fluorescent assay, the method does not suffer from spectral overlap of the encoding method with the assay readout.
These photonic crystals may be used as integral parts of randomly assembled microarrays. These microarrays could be applied in the field of gene expression, genotyping, proteomics, as well as real time chemical and biological sensing.
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SD2003-257
Self-Assembling, Self-Orienting Photonic Crystals of Porous Silicon [Pat. pending]
There are presently many examples of 1-, 2-, and 3-dimensional objects constructed using so-called self-assembly reactions. For example, covalent bonds formed between alkanethiols and gold substrates have been used to pattern surfaces; or hydrogen bonding interactions between DNA base pairs have been used to assemble nanoparticles into complex assemblies. Recently, however, researchers at the University of California , San Diego , have developed a novel technique that allows for the production of optical films with spatially resolved, chemically distinct layers. Although there is literature precedent for a range of surface modifications on porous silicon, the method can dually functionalize the sensors that imparts to them their ability to self-assemble and orient selectively at an interface. The main requirement of the chemical modification reaction used in the functionalization steps is that they be stable to the hydrofluoric etchant used in generating subsequent porous silicon layers. It is anticipated that a number of chemical and electrochemical modification strategies developed for porous silicon can be used with this procedure.
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SD2004-032
Porous Silicon Photonic Crystals Exhibiting Multi-line, Grey-scale Spectra [Pat. pending]
Researchers in the Department of Chemistry & Bio-Chemistry at the University of California , San Diego , have developed a method of optically encoding porous silicon crystals for use in high throughput, highly multiplexed bioassays. The method allows for large libraries of unique particle types to be manufactured. This method is a major advancement in porous silicon interferometric reflectance spectroscopy also developed here (U.S. Pat. 6,248,539). The present invention also allows for signal transduction in bioassays, replacing the need for labeled tags.
The method is a departure from the existing methods of encoding, such as those based on fluorescent molecules, core-shell quantum dots, and previous methods based on Rugate or Bragg reflectivity. These encoding schemes are limited by the number of codes that can be generated within the useful wavelength region.
This method of photonic crystal preparation and bioassay applications has undergone considerable development and is presently available for licensing. Patents pending.
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SD2004-206 and SD2004-270
Magnetic Porous Silicon Photonic Crystals [Pat. pending]
Porous silicon (PSi) is a particularly attractive material for biological and high-tech applications because of the ease with which the optical properties, pore size, and surface chemistry can be manipulated. The position, width and intensity of spectral reflectivity peaks are controlled by current density, waveform and solution composition used in the electrochemical etch. This allows the preparation of PSi photonic crystals that can display any number of colors within the visible spectrum with high color saturation and resolution, highly desirable features for information display. Researchers at the University of California , San Diego , have converted these films into micron-sized particles (so-called “Smart Dust”, described in: Link and Sailor, Smart Dust: Self-assembling, self-orienting photonic crystals of porous Si. ; Proc. Nat. Acad. Sci., 2003, 100 (19): p.10607-10610).
Recently, University researchers have demonstrated magnetically switchable micron-sized photonic crystals that can be induced to flip between a colored photonic crystal face and a black, non-reflective surface in an oscillating magnetic field, at rates exceeding 175 Hz. This property makes this an excellent material for use in display applications.
In addition, magnetic Smart Dust has now been constructed with amphiphilic properties. This allows the micron-size crystals to self-align at the interface between immiscible liquids and effectively encapsulate suspended droplets. The addition of the magnetic property means that the particles can be used to manipulate microliter-scale droplets or cells by the application of an electromagnetic field, without the addition of ions or other impurities to the bulk liquid. Possible application areas include MEMS devices, microfluidic mixing, targeted drug/enzyme delivery, biological screening, and microfluidic tagging.
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SD2005-038 and SDS2005-044
Porous Silicon Photonic Crystals with Light-scattering Domains for Sensing Chemical and Biological Materials [Pat. pending]
UCSD researchers have discovered a method, using porous silicon photonic crystals, to monitor the presence of chemical or biological agents, and even living or dead cells, by looking at light scattering from the crystals when in contact with these materials. The method uses simple and inexpensive light sources and detectors, and does not require time-consuming sample preparation methods nor the use of stains or fluorophores.
This technology has several uses. Because the intensity and spectrum of scattered light changes when the crystals come into contact with chemicals, cells or other materials, it can be used for diagnostics, viability assays, high- or low-throughput drug screening, chemical detection, identification of cell type, monitoring of chemical or biological agents in water or air, drug delivery, and other applications.
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SD2005-088
Porous Photonic Crystals for Intraocular Drug Delivery [Pat. pending]
Problem: The treatment of eye diseases such as Age-related Macular Degeneration, Diabetic Retinopathy, Uveitis and others, has been very problematic. The largest barrier to effective treatment is the difficulty of delivering the appropriate concentration of drug to the correct location in the eye for a sufficient length of time. Various solutions have been attempted, including repeated intraocular injections of drug, or surgical implantation of drug-permeated material. However, these methods are impractical and present a significant risk to the patient: multiple injections are required, each carrying a finite risk of infection, and surgical procedures are cumbersome and not always effective.
Solution Provided by Technology: This invention presents two major advantages over existing ocular drug delivery technologies: (1) The nanoporous silicon, or a biopolymeric cast of it, can be tailor-made for each type of drug , to control the kinetics of sustained drug release such that the drug can be delivered in the eye with the optimal spatio-temporal profile , and over a long period of time. Further, several drugs can be delivered simultaneously, each with its own release parameters. (2) This customized nanomaterial has optical properties that allow one to monitor drug levels in the implant without invasive procedures to the eye . The optical properties of this material change in a reproducible fashion as the concentration of drug decreases within the implant, so that one can view the implant through the iris to determine the amount of drug remaining. These properties make this an ideal material for drug delivery and non-invasive reporting of drug levels.
Benefits: The use of this nano-material minimizes the number of injections required, reducing cost, scarring and the likelihood of infection, and ensures that the patient receives an effective dose throughout the treatment period.
Features: Pore size, spacing and layering can be controlled, and the surface chemistry of the nanoporous silicon or its biopolymeric equivalent can be modified to accommodate almost any type of compound. Further, the optical properties of the material can be customized such that each drug can have its own optical signature, thus allowing one to monitor several drugs simultaneously.
Porous silicon is biocompatible and bioresorbable, and has tunable pore volumes and a high surface area, so that its drug loading capacity is high.
Development Status: Nanoporous silicon has been implanted into the eye and its spectrum visualized through the iris for 4 months or longer, with no obvious toxicity. Nanomaterial has been customized to release dexamethasone into solution. See references for other details.
This invention is available for licensing, sponsored research (see the TransMed Program ).
References: “Polymer Replicas of Photonic Porous Silicon for Sensing and Drug Delivery Applications (2003), Science v. 299, 2045-2047 and “Engineering the Chemistry and Nanostructure of Porous Silicon Fabry-Perot Films for Loading and Release of a Steroid” (2004), Langmuir , v. 20(25), 11264-11269.
http://chem-faculty.ucsd.edu/sailor/research/
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SD2005-090
Method to Fabricate Composite Photonic Crystals of Porous Silicon and Polymers, with Highly Regular Particle Dimensions [Pat. pending]
UCSD researchers have developed an extensive platform of technologies based on porous silicon and/or polymeric nano-particles (“Smart Dust”). This platform encompasses multiple uses of nano-scale particles of porous silicon photonic crystals, and takes advantage of the optical properties and other physical characteristics of this material.
Until now, the simplest methods of making nano-particles of porous silicon have resulted in irregular particle shapes and sizes, and the more complicated fabrication methods, while rendering particles of more consistent quality, were more cumbersome to use for making large quantities of material. The UCSD researchers have now discovered a method to make composite photonic crystals of porous silicon and polymer, on a micron scale, and with a high degree of particle size regularity. This method is simple and inexpensive, and does not require the use of a pre-patterned “master” to determine particle shape or size. The resultant crystals have greatly improved mechanical and chemical stability and are of a more uniform geometry than could be obtained previously.
Porous silicon composites are useful in a number of biological and chemical applications, including chemical and biological sensing, high- and low-throughput screening, drug delivery and diagnostics.
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SD2005-179
Chemical Sensing by RIFTS-Reflective Interferometric Fourier-Transform Spectroscopy: a Robust, Self-compensating Method for Label-free Detection of Biomolecules [Pat. pending]
Problem: Most optical transducers for label-free biosensing involve measurement of a change in the refractive index of a material induced upon analyte binding. While surface plasmon resonance (SPR) films, resonant and nonresonant diffraction gratings, Reflectometric Interference (RIFS) layers and Fabry-Perot interferometers show very sensitive responses to small changes in refractive index, these methods are all limited by zero-point-drift arising from changes in temperature, matrix composition, or nonspecific binding to the analytical surface.
A double-beam (Michelson-type) interferometer, in which one optical path acts as a reference channel, provides an excellent means of compensating for such effects. Various implementations of double-beam correction have been employed in microscale biosensor systems, generally involving two spatially distinct regions of a chip. However, because the sample and reference channels are separated in the X-Y plane, such designs pose significant alignment and manufacturability challenges, especially upon incorporation into high-throughput arrays.
Solution Provided by Technology : This invention utilizes a novel self-compensating interferometric biosensor comprised of two layers of porous SiO 2 , stacked one on top of the other. The reflectivity spectrum displays a complex interference pattern that arises from a combination of Fabry-Pérot interference from these layers. A ratio of the peak intensities in the fast Fourier transform (FFT) allows discrimination of target analyte from matrix effects arising from non-specific compositional changes in the analyte solution.
Benefits and Features: The approach is very general. For example, the methodology should also work with other label-free transduction modalities in materials other than porous SiO 2 or porous Si that utilize refractive index changes, such as surface plasmon resonance or microcavity resonance. The built-in reference channel and Fourier method of analysis provides a general means to compensate for changes in sample matrix, non-specific binding, temperature, and other experimental variables.
Applications: Label-free biosensing, high-throughput molecular sensing, array-based sensing, drug lead discovery, diagnostics, and characterization of kinetic and thermodynamic binding constants in biomolecular binding assays.
Development Status : The concept has been demonstrated with a Protein A capture probe and Human Immunoglobulin G as the target analyte. The system response is shown to be insensitive to the addition of 4000-fold excess sucrose or 80-fold excess bovine serum albumin.
References:
- Lin, H., Mock, J., Smith, D., Gao, T. & Sailor, M. J. Surface-Enhanced Raman Scattering from Silver-Plated Porous Silicon. J. Phys. Chem. B 108 , 11654 -11659 (2004).
- Lin, H., Gao, T., Fantini, J. & Sailor, M. J. A Porous Silicon-Palladium Composite Film for Optical Interferometric Sensing of Hydrogen. Langmuir 20 , 5104-5108 (2004).
- Ghadiri, M. R., Sailor, M. J., Motesharei, K., Lin, S.-Y. & Dancil, K.-P. S. US Patent (2004).
- Gao, J., Gao, T., Li, Y. & Sailor, M. J. Vapor Sensors Based on Optical Interferometry from Oxidized Microporous Silicon Films. Langmuir 18 , 2229-2233 (2002).
- Cunin, F. et al. Biomolecular screening with encoded porous silicon photonic crystals. Nature Mater. 1 , 39-41 (2002).
- Collins, B. E., Dancil, K.-P., Abbi, G. & Sailor, M. J. Determining protein size using an electrochemically machined pore gradient in silicon. Adv. Funct. Mater. 12 , 187-191 (2002).
- Létant, S. & Sailor, M. J. Molecular identification by time resolved interferometry in a porous silicon film. Adv. Mat. 13 , 335-338 (2001).
- Sailor, M. J. et al. in Unattended Ground Sensor Technologies and Applications III (ed. Carapezza, E. M.) 153-165 (SPIE, Orlando , FL , 2001).
- Ghadiri, M. R., Motesharei, K., Lin, S.-Y., Sailor, M. J. & Dancil, K.-P. U. S. Patent ( University of California , San Diego , USA , 2001).
- Létant, S. E., Content, S., Tan, T. T., Zenhausern, F. & Sailor, M. J. Integration of Porous Silicon Chips in an Electronic Artificial Nose. Sens. Actuators B 69 , 193-198 (2000).
- Sohn, H., Létant, S., Sailor, M. J. & Trogler, W. C. Detection of fluorophosphonate chemical warfare agents by catalytic hydrolysis with a porous silicon interferometer. J. Am. Chem. Soc. 122 , 5399-5400 (2000).
- Tinsley-Bown, A. M. et al. Tuning the pore size and surface chemistry of porous silicon for immunoassays. Phys. Status Solidi A 182 , 547-53 (2000).
- Dancil, K.-P. S., Greiner, D. P. & Sailor, M. J. A porous silicon optical biosensor: detection of reversible binding of IgG to a protein A-modified surface. J. Am. Chem. Soc. 121 , 7925-7930 (1999).
- Janshoff, A. et al. Macroporous p-type silicon Fabry-Perot layers. Fabrication, characterization, and applications in biosensing. J. Am. Chem. Soc. 120 , 12108-12116 (1998).
- Lin, V. S.-Y., Motesharei, K., Dancil, K. S., Sailor, M. J. & Ghadiri, M. R. A Porous Silicon-Based Optical Interferometric Biosensor. Science 278 , 840-843 (1997).
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Biological Applications of “Smart Dust” – Porous Silicon Photonic Crystals
(this is a summary of several inventions, described above)
CASE #s: SD1997-064, SD2002-075, SD2003-024; SD2003-257, SD2003-182, SD2003-214, SD2004-032, 2005-038, 2005-044, 2005-088, 2005-090, 2005-179; possibly others.
Summary: UCSD researchers have developed a new nanotechnology (“Smart Dust”) with state-of-the-art applications in almost every field of use, ranging from biological sensing and screening to communications technology.
The invention utilizes micron-sized particles of silicon that have been etched and then chemically modified in such a way that each individual particle has its own addressable identity. This feature allows one to use thousands of the particles together, each with its own “tag”, for high-sensitivity chemical or biological sensing, diagnostics, and low- and high-throughput screening of biomolecular compounds. The method does not require the use of fluorescent tags, but could be used in conjunction with them.
Applications: In addition to those mentioned above, the researchers are currently exploring other biological applications, such as controlled drug release, biomedical implants, artificial organs, and cell-based experimentation platforms.
Inquiries To: invent@ucsd.edu
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