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Purpose To compare patient preferences for eyeglasses prescribed using a low-cost, portable wavefront autorefractor versus standard subjective refraction (SR). Design Randomized, cross-over clinical trial. Participants Patients aged 18 to 40 years presenting with refractive errors (REs) to a tertiary eye hospital in Southern India. Methods Participants underwent SR followed by autorefraction (AR) using the monocular version of the QuickSee device (PlenOptika Inc). An independent optician, masked to the refraction approach, prepared eyeglasses based on each refraction approach. Participants (masked to refraction source) were randomly assigned to use SR- or AR-based eyeglasses first, followed by the other pair, for 1 week each. At the end of each week, participants had their vision checked and were interviewed about their experience with the eyeglasses. Main Outcome Measures Patients preferring eyeglasses were chosen using AR and SR. Results The 400 participants enrolled between March 26, 2018, and August 2, 2019, had a mean (standard deviation) age of 28.4 (6.6) years, and 68.8% were women. There was a strong correlation between spherical equivalents using SR and AR (r = 0.97, P 0.05 for all). Conclusions We observed a strong agreement between the prescriptions from SR and AR, and eyeglasses prescribed using SR and AR were equally preferred by patients. Wider use of prescribing based on AR alone in resource-limited settings is supported by these findings.

To assess the performance of machine learning (ML) ensemble models for predicting patient subjective refraction (SR) using demographic factors, wavefront aberrometry data, and measurement quality related metrics taken with a low-cost portable autorefractor.Four ensemble models were evaluated for predicting individual power vectors (M, JAll models considerably outperformed the predictions from the autorefractor, while ASB obtained the best results. The accuracy of the predictions for each individual power vector component was substantially improved resulting in a ± 0.63 D, ±0.14D, and ±0.08 D reduction in the 95% limits of agreement of the error distribution for M, JThese results suggest that ML is effective for improving precision in predicting patient's SR from objective measurements taken with a low-cost portable device.

To compare patient preferences for eyeglasses prescribed using a low-cost, portable wavefront autorefractor versus standard subjective refraction (SR).Randomized, cross-over clinical trial.Patients aged 18 to 40 years presenting with refractive errors (REs) to a tertiary eye hospital in Southern India.Participants underwent SR followed by autorefraction (AR) using the monocular version of the QuickSee device (PlenOptika Inc). An independent optician, masked to the refraction approach, prepared eyeglasses based on each refraction approach. Participants (masked to refraction source) were randomly assigned to use SR- or AR-based eyeglasses first, followed by the other pair, for 1 week each. At the end of each week, participants had their vision checked and were interviewed about their experience with the eyeglasses.Patients preferring eyeglasses were chosen using AR and SR.The 400 participants enrolled between March 26, 2018, and August 2, 2019, had a mean (standard deviation) age of 28.4 (6.6) years, and 68.8% were women. There was a strong correlation between spherical equivalents using SR and AR (r = 0.97, P0.001) with a mean difference of -0.07 diopters (D) (95% limits of agreement [LoA], -0.68 to 0.83). Of the 301 patients (75.2%) who completed both follow-up visits, 50.5% (n = 152) and 49.5% (n = 149) preferred glasses prescribed using SR and AR, respectively (95% CI, 45.7-56.3; P = 0.86). There were no differences in demographic or vision characteristics between participants with different preferences (P0.05 for all).We observed a strong agreement between the prescriptions from SR and AR, and eyeglasses prescribed using SR and AR were equally preferred by patients. Wider use of prescribing based on AR alone in resource-limited settings is supported by these findings.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited, Purpose To assess the performance of an open-view binocular handheld aberrometer (QuickSee) for diagnosing refractive errors in children. Methods 123 school-age children (9.9 ± 3.3 years) with moderate refractive error underwent autorefraction (AR) with a standard desktop device and subjective refraction (SR), with or without cycloplegia to determine their eyeglass prescription. Measurements with QuickSee (QS) were taken in 62 of these patients without cycloplegia (NC), and in 61 under cycloplegia (C). Differences in refraction values (AR vs SR vs QS) as well as the visual acuity (VA) achieved by the patients with each method (QS vs SR) were used to evaluate the performance of the device in measuring refractive error. Results The spherical equivalent refraction obtained by QS agreed within 0.5 D of the SR in 71% (NC) and 70% (C) of the cases. Agreement between the desktop autorefractor and SR for the same threshold was of 61% (NC) and 77% (C). VA resulting from QS refractions was equal to or better than that achieved by SR procedure in 77% (NC) and 74% (C) of the patients. Average improvement in VA with the QS refractions was of 8.6 and 13.4 optotypes for the NC and C groups respectively, while the SR procedure provided average improvements of 8.9 (NC) and 14.8 (C) optotypes. Conclusions The high level of agreement between QuickSee and subjective refraction together with the VA improvement achieved in both study groups using QuickSee refractions suggest that the device is a useful autorefraction tool for school-age children, Eduardo Lage is funded by the Ramon y Cajal program from the Spanish Ministry of Economy, Industry and Competitivity (RYC-2016-21125). Pablo Perez-Merino was funded by the Juan de la Cierva program from the same Ministry (FJCI-2015-27101). Carlos S. Hernandez and Andrea Gil are funded by the Madrid Regional Government through IND2019/TIC-17116 grant

Significance There is a critical need for tools that increase the accessibility of eye care to address the most common cause of vision impairment: uncorrected refractive errors. This work assesses the performance of an affordable autorefractor, which could help reduce the burden of this health care problem in low-resource communities. Purpose The purpose of this study was to validate the commercial version of a portable wavefront autorefractor for measuring refractive errors. Methods Refraction was performed without cycloplegia using (1) a standard clinical procedure consisting of an objective measurement with a desktop autorefractor followed by subjective refraction (SR) and (2) with the handheld autorefractor. Agreement between both methods was evaluated using Bland-Altman analysis and by comparing the visual acuity (VA) with trial frames set to the resulting measurements. Results The study was conducted on 54 patients (33.9 ± 14.1 years of age) with a spherical equivalent (M) refraction determined by SR ranging from -7.25 to 4.25 D (mean ± SD, -0.93 ± 1.95 D). Mean differences between the portable autorefractor and SR were 0.09 ± 0.39, -0.06 ± 0.13, and 0.02 ± 0.12 D for M, J0, and J45, respectively. The device agreed within 0.5 D of SR in 87% of the eyes for spherical equivalent power. The average VAs achieved from trial lenses set to the wavefront autorefractor and SR results were 0.02 ± 0.015 and 0.015 ± 0.042 logMAR units, respectively. Visual acuity resulting from correction based on the device was the same as or better than that achieved by SR in 87% of the eyes. Conclusions This study found excellent agreement between the measurements obtained with the portable autorefractor and the prescriptions based on SR and only small differences between the VA achieved by either method.

Objective To assess the quality of eyeglass prescriptions provided by an affordable wavefront autorefractor operated by a minimally trained technician in a low-resource setting. Methods and Analysis 708 participants were recruited from consecutive patients registered for routine eye examinations at Aravind Eye Hospital in Madurai, India, or an affiliated rural satellite vision centre. Visual acuity (VA) and patient preference were compared between trial lenses set to two eyeglass prescriptions from (1) a novel wavefront autorefractor and (2) subjective refraction by an experienced refractionist. Results The mean±SD VA was 0.30±0.37, –0.02±0.14 and −0.04±0.11 logarithm of the minimum angle of resolution units before correction, with autorefractor correction and with subjective refraction correction, respectively (all differences p, This work was financially supported by a grant from the United States–India Science & Technology Endowment Fund (USISTEF) awarded jointly to PlenOptika and Aurolab. Financial support for the initial autorefractor development is gratefully acknowledged from Comunidad de Madrid through the Madrid-MIT M+Visión Consortium. Research relating to the autorefractor reported in this publication was partially supported by the National Eye Institute of the National Institutes of Health under Award Number R43EY025452 and R44EY025452

Purpose: Triple coincidences in positron emission tomography (PET) are events in which three γ-rays are detected simultaneously. These events, though potentially useful for enhancing the sensitivity of PET scanners, are discarded or processed without special consideration in current systems, because there is not a clear criterion for assigning them to a unique line-of-response (LOR). Methods proposed for recovering such events usually rely on the use of highly specialized detection systems, hampering general adoption, and/or are based on Compton-scatter kinematics and, consequently, are limited in accuracy by the energy resolution of standard PET detectors. In this work, the authors propose a simple and general solution for recovering triple coincidences, which does not require specialized detectors or additional energy resolution requirements. Methods: To recover triple coincidences, the authors’ method distributes such events among their possible LORs using the relative proportions of double coincidences in these LORs. The authors show analytically that this assignment scheme represents the maximum-likelihood solution for the triple-coincidence distribution problem. The PET component of a preclinical PET/CT scanner was adapted to enable the acquisition and processing of triple coincidences. Since the efficiencies for detecting double and triple events were found to be different throughout the scanner field-of-view, a normalization procedure specific for triple coincidences was also developed. The effect of including triple coincidences using their method was compared against the cases of equally weighting the triples among their possible LORs and discarding all the triple events. The authors used as figures of merit for this comparison sensitivity, noise-equivalent count (NEC) rates and image quality calculated as described in the NEMA NU-4 protocol for the assessment of preclinical PET scanners. Results: The addition of triple-coincidence events with the authors’ method increased peak NEC rates of the scanner by 26.6% and 32% for mouse- and rat-sized objects, respectively. This increase in NEC-rate performance was also reflected in the image-quality metrics. Images reconstructed using double and triple coincidences recovered using their method had better signal-to-noise ratio than those obtained using only double coincidences, while preserving spatial resolution and contrast. Distribution of triple coincidences using an equal-weighting scheme increased apparent system sensitivity but degraded image quality. The performance boost provided by the inclusion of triple coincidences using their method allowed to reduce the acquisition time of standard imaging procedures by up to ∼25%. Conclusions: Recovering triple coincidences with the proposed method can effectively increase the sensitivity of current clinical and preclinical PET systems without compromising other parameters like spatial resolution or contrast.

Although current PET scanners are designed and optimized to detect double coincidence events, there is a significant amount of triple coincidences in any PET acquisition. Triple coincidences may arise from causes such as: inter-detector scatter (IDS), random triple interactions (RT), or the detection of prompt gamma rays in coincidence with annihilation photons when non-pure positron-emitting radionuclides are used (β(+)γ events). Depending on the data acquisition settings of the PET scanner, these triple events are discarded or processed as a set of double coincidences if the energy of the three detected events is within the scanner's energy window. This latter option introduces noise in the data, as at most, only one of the possible lines-of-response defined by triple interactions corresponds to the line along which the decay occurred. Several novel works have pointed out the possibility of using triple events to increase the sensitivity of PET scanners or to expand PET imaging capabilities by allowing differentiation between radiotracers labeled with non-pure and pure positron-emitting radionuclides. In this work, we extended the Monte Carlo simulator PeneloPET to assess the proportion of triple coincidences in PET acquisitions and to evaluate their possible applications. We validated the results of the simulator against experimental data acquired with a modified version of a commercial preclinical PET/CT scanner, which was enabled to acquire and process triple-coincidence events. We used as figures of merit the energy spectra for double and triple coincidences and the triples-to-doubles ratio for different energy windows and radionuclides. After validation, the simulator was used to predict the relative quantity of triple-coincidence events in two clinical scanners assuming different acquisition settings. Good agreement between simulations and preclinical experiments was found, with differences below 10% for most of the observables considered. For clinical scanners and pure positron emitters, we found that around 10% of the processed double events come from triple coincidences, increasing this ratio substantially for non-pure emitters (around 25% for (124)I and > 50% for (86)Y). For radiotracers labeled with (18)F we found that the relative quantity of IDS events in standard acquisitions is around 18% for the preclinical scanner and between 14 and 22% for the clinical scanners. For non-pure positron emitters like (124)I, we found a β(+)γ triples-to-doubles ratio of 2.5% in the preclinical scanner and of up to 4% in the clinical scanners.

Fluorescent semiconductor nanoparticles, or quantum dots, have become a promising platform for the engineering of biofunctional probes for a variety of biomedical applications, ranging from multicolor imaging to single-molecule tracking to traceable drug delivery. Advances in organometallic synthesis have enabled preparation of hydrophobic quantum dots with high quantum yields and narrow size distribution, offering bright optical materials with narrow size-tunable emission profiles. At the same time, polymer encapsulation procedures provided a simple and versatile methodology for transferring hydrophobic nanoparticles into physiologically-relevant aqueous buffers. Taken together, hydrophobic nanoparticle platforms and polymer encapsulation should offer great flexibility for implementation of novel probe designs. However, the success of the encapsulation and purification depends on many factors often overlooked in the scientific literature, such as close match between nanoparticle and polymer physicochemical properties and dimensions, slow dynamics of polymer arrangement on the nanoparticle surface, and the size and charge similarity of resultant polymer-coated quantum dots and empty byproduct polymer micelles. To make this general hydrophobic nanoparticle modification strategy accessible by a broad range of biomedical research groups, we focus on the important technical aspects of nanoparticle polymer encapsulation, purification, bioconjugation, and characterization.

Worldwide, more than one billion people suffer from poor vision because they do not have the eyeglasses they need. Their uncorrected refractive errors are a major cause of global disability and drastically reduce productivity, educational opportunities, and overall quality of life. The problem persists most prevalently in low-resource settings, even though prescription eyeglasses serve as a simple, effective, and largely affordable solution. In this review, we discuss barriers to obtaining, and approaches for providing, refractive eye care. We also highlight emerging technologies that are being developed to increase the accessibility of eye care. Finally,we describe opportunities that exist for engineers to develop new solutions to positively impact the diagnosis and treatment of correctable refractive errors in low-resource settings. Copyright © 2014 by Annual Reviews. All rights reserved., Financial support from the Madrid-MIT M+Vision Consortium and the MIT MISTI-India Global Seed Fund.

Fluorescent cytometry refers to the quantification of cell physical properties and surface biomarkers using fluorescently-tagged antibodies. The generally preferred techniques to perform such measurements are flow cytometry, which performs rapid single cell analysis by flowing cells one-by-one through a channel, and microscopy, which eliminates the complexity of the flow channel, offering multi-cell analysis at a lesser throughput. Low-magnification image-based cytometers, also called “cell astronomy” systems, hold promise of simultaneously achieving both instrumental simplicity and high throughput. In this magnification regime, a single cell is mapped to a handful of pixels in the image. While very attractive, this idea has, so far, not been proven to yield quantitative results of cell-labeling, mainly due to the poor signal-to-noise ratio present in those images and to partial volume effects. In this work we present a cell astronomy system that, when coupled with custom-developed algorithms, is able to quantify cell intensities and diameters reliably. We showcase the system using calibrated MESF beads and fluorescently stained leukocytes, achieving good population identification in both cases. The main contribution of the proposed system is in the development of a novel algorithm, H-EM, that enables inter-cluster separation at a very low magnification regime (2x). Such algorithm provides more accurate brightness estimates than DAOSTORM when compared to manual analysis, while fitting cell location, brightness, diameter, and background level concurrently. The algorithm first performs Fisher discriminant analysis to detect bright spots. From each spot an expectation-maximization algorithm is initialized over a heterogeneous mixture model (H-EM), this algorithm recovers both the cell fluorescence and diameter with sub-pixel accuracy while discriminating the background noise. Finally, a recursive splitting procedure is applied to discern individual cells in cell clusters.

Surface engineering advances of semiconductor quantum dots (QDs) have enabled their application to molecular labeling, disease diagnostics and tumor imaging. For biological applications, hydrophobic core/shell QDs are transferred into aqueous solutions through the incorporation of water-solubility imparting moieties, typically achieved via direct exchange of the native surface passivating ligands or indirectly through the adsorption of polymers. Although polymeric encapsulation has gained wide acceptance, there are few reports addressing the characterization of the adsorbed polymers and existing theoretical analyses are typically based on simple geometric models. In this work, we experimentally characterize and quantify water-soluble QDs prepared by adsorption of amphiphilic poly(maleic anhydride-alt-1-tetradecene) (PMAT, MW ~ 9000) onto commercially available CdSe/CdS/ZnS (CdSe/CdS/ZnS-PMAT). Using X-ray photoelectron spectroscopy (XPS) we determined that ~ 15 PMAT molecules are adsorbed onto each QD and sum frequency generation (SFG) vibrational spectra were utilized to investigate the mechanism of interaction between PMAT molecules and the QD surface. Importantly, when employed together, these techniques constitute a platform with which to investigate any polymer–nanoparticle complex in general.

Advances in nanotechnology have pushed forward the synthesis of a variety of functional nanoparticles (NPs) such as semiconductor quantum dots (QDs), magnetic and metallic NPs. The unique electronic, magnetic, and optical properties exhibited by these nanometer-sized materials have enabled a broad spectrum of biomedical applications. In particular, iron-oxide-based magnetic NPs have proved to be highly versatile deep-tissue imaging agents, having been incorporated into clinical applications due to their biocompatibility. This Interdisciplinary Review will focus on the recent advances in strategies for the synthesis and surface modification of highly monodisperse magnetic NPs and their use in imaging, drug delivery, and innovative ultrasensitive bioassays.

Triple coincidences in positron emission tomography (PET) are events in which three γ-rays are detected simultaneously. These events, though potentially useful for enhancing the sensitivity of PET scanners, are discarded or processed without special consideration in current systems, because there is not a clear criterion for assigning them to a unique line-of-response (LOR). Methods proposed for recovering such events usually rely on the use of highly specialized detection systems, hampering general adoption, and/or are based on Compton-scatter kinematics and, consequently, are limited in accuracy by the energy resolution of standard PET detectors. In this work, the authors propose a simple and general solution for recovering triple coincidences, which does not require specialized detectors or additional energy resolution requirements.To recover triple coincidences, the authors' method distributes such events among their possible LORs using the relative proportions of double coincidences in these LORs. The authors show analytically that this assignment scheme represents the maximum-likelihood solution for the triple-coincidence distribution problem. The PET component of a preclinical PET/CT scanner was adapted to enable the acquisition and processing of triple coincidences. Since the efficiencies for detecting double and triple events were found to be different throughout the scanner field-of-view, a normalization procedure specific for triple coincidences was also developed. The effect of including triple coincidences using their method was compared against the cases of equally weighting the triples among their possible LORs and discarding all the triple events. The authors used as figures of merit for this comparison sensitivity, noise-equivalent count (NEC) rates and image quality calculated as described in the NEMA NU-4 protocol for the assessment of preclinical PET scanners.The addition of triple-coincidence events with the authors' method increased peak NEC rates of the scanner by 26.6% and 32% for mouse- and rat-sized objects, respectively. This increase in NEC-rate performance was also reflected in the image-quality metrics. Images reconstructed using double and triple coincidences recovered using their method had better signal-to-noise ratio than those obtained using only double coincidences, while preserving spatial resolution and contrast. Distribution of triple coincidences using an equal-weighting scheme increased apparent system sensitivity but degraded image quality. The performance boost provided by the inclusion of triple coincidences using their method allowed to reduce the acquisition time of standard imaging procedures by up to ∼25%.Recovering triple coincidences with the proposed method can effectively increase the sensitivity of current clinical and preclinical PET systems without compromising other parameters like spatial resolution or contrast.

In the pursuit of sensitive and quantitative methods to detect and diagnose cancer, nanotechnology has been identified as a field of great promise. Semiconductor quantum dots are nanoparticles with intense, stable fluorescence, and could enable the detection of tens to hundreds of cancer biomarkers in blood assays, on cancer tissue biopsies, or as contrast agents for medical imaging. With the emergence of gene and protein profiling and microarray technology, high-throughput screening of biomarkers has generated databases of genomic and expression data for certain cancer types, and has identified new cancer-specific markers. Quantum dots have the potential to expand this in vitro analysis, and extend it to cellular, tissue and whole-body multiplexed cancer biomarker imaging.

The metal radionuclides 60Cu (T 1/2 = 23 min), 52mMn (T 1/2 = 21 min) and 94mTc (T 1/2 = 53 min) can be used to label tracers of high clinical and preclinical interest in PET studies. Furthermore, as they emit prompt gamma-rays right after the positron emission, they can be distinguished from standard positron emitters like 18F, enabling multiplexed PET (mPET) imaging. In this work we studied the feasibility of their production using a relatively low-energy (10 MeV) proton beam from a linear accelerator. These radionuclides were produced by bombardment on target foils of natural Nickel, Chromium and Molybdenum respectively. After activation, the emissions from the foils were analyzed by a Ge spectrometer and the absolute activity for each produced species was obtained. The activity generated was in agreement with the expected cross-sections and the isotopes present in the samples. These results show the feasibility of production of these radionuclides with a 10 MeV proton beam.

Most PET scanners are designed to detect and record gamma-ray coincidences from the annihilation of positrons coming from radiotracers. Multiple coincidences, those for which more than two gamma-rays are detected within the coincidence time window, are usually discarded. Those events can be registered and used to increase the sensitivity of the scanner and to differentiate positron-gamma emitters from pure positron emitters, enabling multiplexed PET. To assess the effect of triple coincidences in PET scanners, an accurate and reliable simulation toolkit is compulsory. In this work we extend and validate the Monte Carlo (MC) simulator PeneloPET to deal with multiple-coincidences in PET scanners. Details of gamma-rays cascades from several positron-gamma emitters, such as 124I, were incorporated in the simulation. Furthermore, a new tool to analyze doubles and triples datasets generated by the simulation was added to the software package. Results from simulations were first compared against data acquired with a modified version of the preclinical Argus PET/CT scanner (Sedecal S.A., Madrid, Spain), which is enabled to acquire and process multiple coincidence events. A good agreement in the energy spectra as well as in the double/triples ratio between simulations and experiments was found (differences below 10 %). Once validated, the simulator was used to evaluate the feasibility of using multiple-coincidence events in several clinical PET/CT scanners, such as the Siemens Biograph TruePoint TrueV (B-TPTV), the GE Discovery-690 and the Philips Ingenuity scanners.

Recent developments in nanotechnology have made available a host of new approaches for the improved quantitative detection of biomarkers due to the enhanced sensitivity of nanoparticle-based assays. The majority of molecular toxicology studies revolve around sensitive measurement of cell-death (apoptosis) and cell-health biomarkers present in living cells or formalin-fixed and paraffin embedded (FFPE) tissue samples. In this regard, semi-conductor quantum dots (QDs) which exhibit high brightness, photo-stability and degree of multiplexing, are predicted to have a significant impact on research in molecular toxicology. Due to these superior photophysical properties of QDs as compared to traditional fluorophores and the unsurpassed versatility of QDs as enabling components for new assays, these nanoparticles promise to facilitate new discoveries in molecular toxicology. Indeed, multiplexed QD-based assays have been incorporated into cell imaging, flow cytometry and other homogenized sample-based assays for detecting multiple biomarkers including those associated with cell injury and apoptosis.

Recent developments in nanotechnology have made available a host of new approaches for the improved quantitative detection of biomarkers due to the enhanced sensitivity of nanoparticle-based assays. The majority of molecular toxicology studies revolve around sensitive measurement of cell-death (apoptosis) and cell-health biomarkers present in living cells or formalin-fixed and paraffin embedded (FFPE) tissue samples. In this regard, semi-conductor quantum dots (QDs) which exhibit high brightness, photo-stability and degree of multiplexing, are predicted to have a significant impact on research in molecular toxicology. Due to these superior photophysical properties of QDs as compared to traditional fluorophores and the unsurpassed versatility of QDs as enabling components for new assays, these nanoparticles promise to facilitate new discoveries in molecular toxicology. Indeed, multiplexed QD-based assays have been incorporated into cell imaging, flow cytometry and other homogenized sample-based assays for detecting multiple biomarkers including those associated with cell injury and apoptosis.

In the biological sciences the use of core-shell quantum dots (QDs) has gained wide usage, but analytical challenges still exist for characterizing the QD structure. The application of energy-dispersive x-ray spectroscopy and x-ray photoelectron spectroscopy (XPS) to bulk materials is relatively straightforward, however, for meaningful applications of surface science techniques to multilayer nanoparticles requires novel modifications and analysis methods. To experimentally characterize the elemental composition and distribution in CdSe/CdS/ZnS QDs, we first develop a XPS signal subtraction technique capable of separating the overlapped selenium 3s (core) and sulfur 2s (shell) peaks (both peaks have binding energies near 230eV) with higher precision than is typically reported in the nanoparticle literature. This method is valid for any nanoparticle containing selenium and sulfur. Then we apply a correction formula to the XPS data and determine that the 2 nm stoichiometric CdSe core is surrounded by 2 CdS layers and a stoichimetric ZnS monolayer. These findings and the multi-approach methodology represent a significant advancement in the detailed surface science study of multi-layer nanoparticles. In agreement with recent surprising findings, the time-of-flight secondary mass spectrometry measurements suggest that the surface sites of the QDs used in this study are primarily covered with a mixture of octadecylphosphonic acid and trioctylphophine oxide.

Advances in nanotechnology have pushed forward the synthesis of a variety of functional nanoparticles (NPs) such as semiconductor quantum dots (QDs), magnetic and metallic NPs. The unique electronic, magnetic, and optical properties exhibited by these nanometer-sized materials have enabled a broad spectrum of biomedical applications. In particular, iron-oxide-based magnetic NPs have proved to be highly versatile deep-tissue imaging agents, having been incorporated into clinical applications due to their biocompatibility. This Interdisciplinary Review will focus on the recent advances in strategies for the synthesis and surface modification of highly monodisperse magnetic NPs and their use in imaging, drug delivery, and innovative ultrasensitive bioassays.

Multiplexed nanobarcodes have been prepared with quantum dots (QDs) and alternating amphiphilic copolymers consisted of hydrocarbons and maleic anhydride groups. In homogenous solution, the QD-polymer complexes grow epitaxially into nanobeads of narrow size dispersity, which has been previously achieved only for micrometer-sized beads in the presence of solid supports. As a result of this new nanostructure formation mechanism, more than 250 QDs can be loaded into a nanobead of 100 nm in diameter. A model assay for sensitive detection of human prostate specific antigen (PSA) has also been demonstrated using the QD-nanobeads as fluorescent reporters. This nanoparticle-polymer self-assembly technology is capable of producing a variety of nanostructures and is expected to open new opportunities in nanoparticle-based ultrasensitive detection and imaging.

Quantum dots (QDs), tiny light-emitting particles on the nanometer scale, are emerging as a new class of fluorescent probes for biomolecular and cellular imaging. In comparison with organic dyes and fluorescent proteins, quantum dots have unique optical and electronic properties such as size-tunable light emission, improved signal brightness, resistance against photobleaching, and simultaneous excitation of multiple fluorescence colors. These properties are most promising for improving the sensitivity of molecular imaging and quantitative cellular analysis by 1-2 orders of magnitude. Recent advances have led to multifunctional nanoparticle probes that are highly bright and stable under complex in-vivo conditions. A new structural design involves encapsulating luminescent QDs with amphiphilic block copolymers, and linking the polymer coating to tumor-targeting ligands and drug-delivery functionalities. Polymer-encapsulated QDs are essentially nontoxic to cells and small animals, but their long-term in-vivo toxicity and degradation need more careful studies. Nonetheless, bioconjugated QDs have raised new possibilities for ultrasensitive and multiplexed imaging of molecular targets in living cells and animal models.

Quantum dots (QDs), tiny light-emitting particles on the nanometer scale, are emerging as a new class of fluorescent probes for biomolecular and cellular imaging. In comparison with organic dyes and fluorescent proteins, quantum dots have unique optical and electronic properties such as size-tunable light emission, improved signal brightness, resistance against photobleaching, and simultaneous excitation of multiple fluorescence colors. These properties are most promising for improving the sensitivity of molecular imaging and quantitative cellular analysis by 1-2 orders of magnitude. Recent advances have led to multifunctional nanoparticle probes that are highly bright and stable under complex in-vivo conditions. A new structural design involves encapsulating luminescent QDs with amphiphilic block copolymers, and linking the polymer coating to tumor-targeting ligands and drug-delivery functionalities. Polymer-encapsulated QDs are essentially nontoxic to cells and small animals, but their long-term in-vivo toxicity and degradation need more careful studies. Nonetheless, bioconjugated QDs have raised new possibilities for ultrasensitive and multiplexed imaging of molecular targets in living cells and animal models.