Intrinsic Sensitivity Research Articles

In-vitro NMR Studies of Prostate Tumor Cell Metabolism by Means of Hyperpolarized [1-13C]Pyruvate Obtained Using the PHIP-SAH Method.

Nuclear Magnetic Resonance allows the non-invasive detection and quantitation of metabolites to be carried out in cells and tissues. This means that that metabolic changes can be revealed without the need for sample processing and the destruction of the biological matrix. The main limitation to the application of this method to biological studies is its intrinsic low sensitivity. The introduction of hyperpolarization techniques and, in particular, of dissolution-Dynamic Nuclear Polarization (d-DNP) and ParaHydrogen Induced Polarization (PHIP) is a significant breakthrough for the field as the MR signals of molecules and, most importantly, metabolites, can be increased by some orders of magnitude. Hyperpolarized pyruvate is the metabolite that has been most widely used for the investigation of metabolic alterations in cancer and other diseases. Although d-DNP is currently the gold-standard hyperpolarization method, its high costs and intrinsically slow hyperpolarization procedure are a hurdle to the application of this tool. However, PHIP is cost effective and fast and hyperpolarized pyruvate can be obtained using the so-called Side Arm Hydrogenation approach (PHIP-SAH). The potential toxicity of a solution of the hyperpolarized metabolite that is obtained in this way is presented herein. HP pyruvate has then been used for metabolic studies on different prostate cancer cells lines (DU145, PC3, and LnCap). The results obtained using the HP metabolite have been compared with those from conventional biochemical assays.

Deletion of Mouse Setd4 Promotes the Recovery of Hematopoietic Failure

Acquired hematopoietic failure is commonly caused by therapeutic and accidental exposure of the bone marrow (BM) to toxic agents. Efficient recovery from BM failure is dictated not only by the intrinsic sensitivity and proliferation capacity of the hematopoietic stem and progenitor cells but also by the BM environment niche. Identification of genetic factors that improve recovery from hematopoietic failure is essential. Vertebrate SETD4 is a poorly characterized and putatively nonhistone methyltransferase. This study aims to identify the roles of SETD4 in BM recovery. An inducible SETD4 knockout mouse model (Setd4flox/flox;Rosa26-CreERT2+) was used. Adult sex-matched littermates were treated with tamoxifen to induce Setd4 deletion or oil as the control. Tamoxifen-treated Setd4wt/wt;Rosa26-CreERT2+ mice were included as another control. Those mice were irradiated to induce hematopoietic syndrome and analyzed to identify the roles and mechanisms of Setd4 in of BM recovery. Loss of Setd4 in adult mice improved the survival of whole-body irradiation-induced BM failure. This was associated with improved recoveries of long-term and short-term hematopoietic stem cells (HSCs) and early progenitor cells. BM transplantation analyses surprisingly showed that the improved recovery was not due to radiation resistance of the Setd4-deficient HSCs but that Setd4-deficient HSCs were actually more sensitive to radiation. However, the Setd4-deficient mice were better recipients for allogeneic HSC transplantation. Furthermore, there was enhanced splenic erythropoiesis in Setd4-deficient mice. These findings not only revealed a previously unrecognized role of Setd4 as a unique modulator of hematopoiesis but also underscored the critical role of the BM niche in recovery from hematopoietic failure. Our study also implicated Setd4 as a potential target for therapeutic inhibition to improve the conditioning of the BM niche before allogeneic transplantation.

Optogenetic restoration of retinal ganglion cell activity in the living primate

Optogenetic therapies for vision restoration aim to confer intrinsic light sensitivity to retinal ganglion cells when photoreceptors have degenerated and light sensitivity has been irreversibly lost. We combine adaptive optics ophthalmoscopy with calcium imaging to optically record optogenetically restored retinal ganglion cell activity in the fovea of the living primate. Recording from the intact eye of a living animal, we compare the patterns of activity evoked by the optogenetic actuator ChrimsonR with natural photoreceptor mediated stimulation in the same retinal ganglion cells. Optogenetic responses are recorded more than one year following administration of the therapy and two weeks after acute loss of photoreceptor input in the living animal. This in vivo imaging approach could be paired with any therapy to minimize the number of primates required to evaluate restored activity on the retinal level, while maximizing translational benefit by using an appropriate pre-clinical model of the human visual system.

Coupling Electrophysiology with Single Cell RNA Sequencing to Uncover Transcriptional Markers of Chemosensitive Serotonergic Neurons

Central respiratory chemoreceptors are specialized neurons with intrinsic sensitivity to hypercapnia and/or acidosis that couple breathing and pH/CO2 levels. Previous data support the hypothesis that a sub‐population of brainstem serotonin (5‐HT) neurons serve as central respiratory chemoreceptors, where they become sensitive to pH/CO2 on or after post‐natal day 12 (P12) in rats. However, to date it remains unclear which 5‐HT neurons develop chemosensitivity and what molecular markers may identify this unique sub‐population of 5‐HT neurons. To address these questions, we employed a “patch‐to‐seq” technique to first distinguish 5‐HT neurons as chemosensitive (or insensitive) using electrophysiologic recording, and then to isolate each neurons’ RNA for single cell RNA Sequencing to identify potential cellular sensing mechanisms and/or unique transcriptional markers in each phenotypically‐identified 5‐HT neuron population. Acute brainstem slices (200 μm) were made from young (P18–23) transgenic rats which express eGFP in all 5‐HT neurons (SSeGFP), and action potential firing rates measured via a cell‐attached patch configuration in eGFP+ 5‐HT neurons during superfusion with artificial CSF (aCSF) containing inhibitors for synaptic blockade (10 mM CNQX, 50 mM D‐AP5, 20 mM Gabazine) bubbled with either 5% CO2 (bal. O2; pH= 7.36; 5 min) or 15% CO2 (bal. O2; pH= 7.10). Cellular phenotypes were assessed by calculating a Chemosensitivity Index (C.I.). pH‐sensitive eGFP+ neurons (n=7) had an average C.I. of 177.0±14.6 whereas pH‐insensitive eGFP+ neurons (n=9) had an average C.I. of 98.0 ± 2.9 (P < 0.0001). Cellular contents of each recorded cell were collected and subjected to single cell RNA Sequencing (scRNA‐Seq), from which an average of 19.3M reads were generated with a quality score of ~33.7 and ~83% mapping rate per sample (32,883 known genes quantified). Preliminary analyses indicate very few differentially expressed genes (q < 0.05) between pH‐sensitive and ‐ insensitive 5‐HT neuron populations, and of those differentially expressed no gene obviously contributes to pH regulation or sensing. In addition, unbiased hierarchical clustering and principal component analyses failed to clearly separate samples by phenotype. However, a supervised analysis using Support Vector Machine learning and Recursive Feature Elimination (SVM‐RFE) identified several genes in which expression levels significantly predict the predefined phenotype, but the biological/functional significance of these genes in CO2/pH sensing remains unclear and instead these genes may provide a molecular signature to distinguish pH/CO2 sensitive vs insensitive 5‐HT neurons. We conclude from these preliminary data that pH/CO2 sensitivity in 5‐HT neurons is not a transcriptionally regulated phenotype.Support or Funding InformationParker B. Francis FoundationNHLBI ‐ R01 HL122358

Theoretical and experimental results of optically pumped sodium atoms

Optical pumping is a process that produces a nonthermal Zeeman sublevel population distribution. It plays an important role in alkali-metal magnetometers for two uses, constructing the sub-Doppler features to lock the laser frequency and providing the spin-polarized atoms to precess around the magnetic field. To comprehensively study the properties of sodium (Na) magnetometer, we present the detailed theoretical analysis of the saturated absorption spectroscopy (SAS) and the magneto-optical resonance signal in sodium D2 line. Accordingly, we have implemented two experimental schemes, the counter propagating pump-probe SAS of thermal Na vapor and the remote sensing Bell-Bloom magnetometry based on the Larmor precession frequency. In the first experiment, sub-Doppler features of D2 consist of two velocity selective optical pumping (VSOP) resonances located at the D2a and D2b transitions and a crossover (CO) resonance located between the VSOP resonances are observed. In the second experiment, an estimated intrinsic magnetometric sensitivity of δBint=286 pT in a 1 Hz bandwidth, is achieved by demodulating the recorded fluorescence signal of the resultant magneto-optical resonance near the 300 kHz Larmor precession frequency. Both kinds of experimental results are in good agreement with our theoretical calculations.

Malignant Cutaneous Melanoma: Updates in PET Imaging.

Cutaneous malignant melanoma is a neoplasm whose incidence and mortality are dramatically increasing. 18F-FDG PET/CT gained clinical acceptance over the past 2 decades in the evaluation of several glucose-avid neoplasms, including malignant melanoma, particularly for the assessment for distant metastases, recurrence and response to therapy. To describe the advancements of nuclear medicine for imaging melanoma with particular attention to 18F-FDG-PET and its current state-of-the-art technical innovations. A comprehensive search strategy was used based on SCOPUS and PubMed databases. From all studies published in English, we selected the articles that evaluated the technological insights of 18FFDG- PET in the assessment of melanoma. State-of-the-art silicon photomultipliers based detectors ("digital") PET/CT scanners are nowadays more common, showing technical innovations that may have beneficial implications for patients with melanoma. Steady improvements in detectors design and architecture, as well as the implementation of both software and hardware technology (i.e., TOF, point spread function, etc.), resulted in significant improvements in PET image quality while reducing radiotracer dose and scanning time. Recently introduced digital PET detector technology in PET/CT and PET/MRI yields higher intrinsic system sensitivity compared with the latest generation analog technology, enabling the detection of very small lesions with potential impact on disease outcome.

Applications of dielectric pads, novel materials and resonators in 1.5T and 3T MRI

In order to boost the performance of magnetic resonance imaging without increasing the static magnetic field, it is necessary to increase its intrinsic sensitivity. This allows a reduction in the scanning time, increased spatial resolution, and can enable low-field strength systems (which are much cheaper and can be used to scan patients with metallic implants) to have a higher signal-to-noise ratio (SNR) so that they are comparable to more expensive higher field strength systems. In this contribution, we demonstrate radiofrequency field enhancing and shaping devices based on novel materials, such as high permittivity dielectric structures and metamaterials. These materials can substantially enhance SNR, thus potentially increasing image resolution or allowing faster examinations.

A Methodological Approach to Determine Sound Response Modalities to Coastal Erosion Processes in Mediterranean Andalusia (Spain)

Human occupation along coastal areas has been greatly increasing in recent decades and, in many places, human activities and infrastructures are threatened by erosion processes that can produce relevant economic and human losses. In order to reduce such impacts and design sound management strategies, which can range from the “no action” to the “protection” option, coastal managers need to know the intrinsic coastal sensitivity and the potential vulnerability and value of land uses. In this paper, in a first step, coastal sensitivity was determined by calculating the following: (i) the spatial distribution at the coast of the wave forcing obtained by using the ERA5 wave dataset and defined as the energy associated with the 50-year return period storm. Two storm conditions were considered, that is, one for the eastern and one for the western parts of the Andalusia Mediterranean coast, respectively, characterized by a height of 8.64–7.86 m and 4.85–4.68 m and (ii) the existence of a buffer zone, namely the dry beach width expressed as a multiple of the 20-year predicted shoreline position that was calculated using a dataset of aerial photographs covering a time span from 1956 to 2016. Coastal sensitivity values were divided into five classes with class 1 indicating the lowest sensitivity (i.e., the presence of a wide buffer zone associated with low wave energy flux values) and class 5 the highest sensitivity (i.e., a narrow buffer zone associated with very high wave energy flux values). In a second step, land uses were obtained from the official Land Use Map of the Andalusia Region, based on the results of the “Coordination of Information on the Environment” (CORINE) European Project. Such uses were divided into five classes from class 1 including natural areas (typologies “A” and “B” of the CORINE Project) to class 5 including very capital land uses (typologies “E1” and “E2”). In a third step, information concerning coastal sensitivity and land uses was crossed to determine the best mitigation strategies to cope with erosion processes. The “no action” option was observed at the westernmost area of Cádiz Province and at some areas from the west coast of Almería Province, where both coastal sensitivity and land use classes show low values; the “adaptation” option was recorded along more than one half of the coast studied, essentially at natural areas with high sensitivity and at urbanized areas with low sensitivity; and the “protection” option was observed especially at some areas from the center and eastern part of Málaga Province and at the easternmost areas of Almería Province, where both coastal sensitivity and land use classes presented high values.

Amino Acid Polymorphism in Succinate Dehydrogenase Subunit C Involved in Biological Fitness of Botrytis cinerea.

Succinate dehydrogenase (SDH) is an important respiratory enzyme which participates in the tricarboxylic acid cycle and oxidative phosphorylation. A previous study of the baseline sensitivity of Botrytis cinerea against SDH inhibitors (SDHIs) showed that intrinsic sensitivity of the small population against the SDHIs exhibited significant differences. In the sequencing assay, we found five kinds of amino acid polymorphism in SDH subunit C (SdhC) of B. cinerea isolates which were never exposed to the SDHIs. To validate that amino acid polymorphism in the SdhC of B. cinerea confers intrinsic sensitivity against the SDHIs, the replacement mutants containing each kind of amino acid polymorphism of SdhC exhibited phenotype differences in intrinsic sensitivity to SDHIs, mycelial growth, sporulation, virulence, oxidative stress response, and carbon source utilization. These results indicated that SdhC of B. cinerea experienced positive selection during evolution and resulted in amino acid polymorphism which is involved in intrinsic sensitivity to SDHIs and biological fitness.

Noise-based ballistic wave passive seismic monitoring. Part 1: body waves

SUMMARY Unveiling the mechanisms of earthquake and volcanic eruption preparation requires improving our ability to monitor the rock mass response to transient stress perturbations at depth. The standard passive monitoring seismic interferometry technique based on coda waves is robust but recovering accurate and properly localized P- and S-wave velocity temporal anomalies at depth is intrinsically limited by the complexity of scattered, diffracted waves. In order to mitigate this limitation, we propose a complementary, novel, passive seismic monitoring approach based on detecting weak temporal changes of velocities of ballistic waves recovered from seismic noise correlations. This new technique requires dense arrays of seismic sensors in order to circumvent the bias linked to the intrinsic high sensitivity of ballistic waves recovered from noise correlations to changes in the noise source properties. In this work we use a dense network of 417 seismometers in the Groningen area of the Netherlands, one of Europe's largest gas fields. Over the course of 1 month our results show a 1.5 per cent apparent velocity increase of the P wave refracted at the basement of the 700-m-thick sedimentary cover. We interpret this unexpected high value of velocity increase for the refracted wave as being induced by a loading effect associated with rainfall activity and possibly canal drainage at surface. We also observe a 0.25 per cent velocity decrease for the direct P-wave travelling in the near-surface sediments and conclude that it might be partially biased by changes in time in the noise source properties even though it appears to be consistent with complementary results based on ballistic surface waves presented in a companion paper and interpreted as a pore pressure diffusion effect following a strong rainfall episode. The perspective of applying this new technique to detect continuous localized variations of seismic velocity perturbations at a few kilometres depth paves the way for improved in situ earthquake, volcano and producing reservoir monitoring.

TR-DLS analysis on analog circuit

Analog circuits are often challenging to debug with dynamic laser stimulation (DLS) due to intrinsic sensitivity of some circuitries to carrier generations. This paper showcases successful post‑silicon debug on analog circuitries (start-up circuit) using nanosecond pulse-on-demand laser to perform Time-resolved Dynamic Laser Stimulation (TR-DLS), leading into root cause identification on a marginality issue in a sub-20 nm FinFET technology device.

Modulating the Human Basophil Phenotype During Its Development and Maturation: Basophils Derived from In Vitro Cultures of CD34+ Progenitor Cells.

Historically, the human basophil that is studied experimentally comes from peripheral blood. But there is evidence that only a short portion of the basophil life cycle related to IgE-mediated function occurs in the blood. The same evidence suggests that IgE-mediated functionality is present for 5-7days in the bone marrow (or other tissues) during which the cell modulates its phenotype according to local conditions. It is suggested that to properly understand the nature of basophil behavior, a better understanding of its biology during maturation would be helpful. For example, one highly suggestive line of evidence for the relevance of understanding the maturation period is related to the change in basophil phenotype that occurs during treatment of patients with omalizumab. During this treatment, the intrinsic reactivity or sensitivity of the basophils is significantly increased despite, or perhaps because of, the dramatic reduction in FcεRI expression that accompanies this treatment. One of the critical signaling enzymes to increase expression selectively in basophils during treatment is SYK, which is one of the earliest signaling tyrosine kinases involved in translating the aggregation of FcεRI into secretion from the cell. Treatment with omalizumab increases SYK expression, and this observation focuses some attention of how SYK expression is regulated. It is possible that the key regulation occurs during maturation of the basophil. Regardless of the mechanisms operative in this particular treatment, understanding the process of maturation and the extrinsic factors that influence it may lead to better understanding of disease processes. Therefore, this chapter will discuss and present techniques to work with maturing human basophils.

Steam-based thermotherapy for managing nematodes in strawberry transplants.

Aerated steam-based thermotherapy was developed and evaluated for its efficacy in managing three nematode species (Aphelenchoides besseyi, Meloidogyne hapla, and Pratylenchus penetrans) that are often transported as quiescent passengers on strawberry transplants shipped to Florida from out-of-state nurseries. Initial studies were focused on evaluating the intrinsic temperature sensitivity of each nematode species to hot water in laboratory conditions. Each nematode species was exposed to hot water at 40, 44, 48, and 52°C for 1, 5, 10, 30, 60, 120, and 240 min. Exposure for 60 min or higher at 40°C paralyzed all three nematode species when examined immediately after heat treatment. Examination of the nematodes 24 hr post-treatment suggested that 100% mortality of all three nematode species was achieved when nematodes were exposed to hot water at a minimum temperature of 44°C for 120 min. Further studies were conducted to evaluate the efficacy of aerated steam to kill all three nematode species by exposing nematode-infested strawberry transplants at 44°C for 60, 120, and 240 min. Exposure of nematode inoculated plants to steam for 60 or 120 min reduced the populations of all three nematode species, but this was not enough to completely eradicate any of the three nematode species. Exposure for 240 min, however, was the most effective in reducing the populations of the three nematode species. A 240 min of exposure to aerated steam completely eradicated A. besseyi and M. hapla while P. penetrans populations were reduced only by 85%. Furthermore, the aerated steam had minimal to no adverse effect on plant biomass. Results from both the laboratory and greenhouse studies indicated that M. hapla was more sensitive to heat treatment followed by A. besseyi and P. penetrans. Results from this study suggested that aerated steam-based thermotherapy has good potential as a non-chemical method of management of nematodes of strawberry transplants.

A microwell array structured surface plasmon resonance imaging gold chip for high-performance label-free immunoassay.

Surface plasmon resonance imaging (SPRi) offers a compelling method for high-throughput, real-time, and label-free biomolecular interaction studies and immunoassays, but its performance suffers from limited intrinsic sensitivity and low-contrast SPRi images. Herein we report a high-performance SPRi chip featuring patterned microwell array constructed by photolithography of adhesive polydopamine (PDA) thin film on conventional gold chip. The chip allows for the facile construction of region-defined sensing array on its surface with improved intrinsic SPRi sensitivity due to the intensified surface plasmon wave (SPW) in the microwells. The immunoassay performance of the as-designed SPRi chip is evaluated by using anti-ochratoxin A (anti-OTA) monoclonal antibody as a model target. The results show that this microwell array structured gold chip exhibits ca. 18%-32% higher signal intensity than the conventional gold chip when detecting anti-OTA at different concentrations, and the noise remains at the same level, showing enhanced intrinsic sensitivity. Meanwhile, this microwell-structured chip affords clear and high-contrast SPRi images with well-defined sensing areas, which greatly facilitates the extraction and quantitative analysis of detection signals while efficiently suppressing the disturbance from background areas.

A semi-interpenetrating network ionic hydrogel for strain sensing with high sensitivity, large strain range, and stable cycle performance

Transparent conductive hydrogels with intrinsic flexibility, high sensitivity and outstanding repeatability and nearly real-time response are highly demanded for wearable devices/sensors. Here we report a novel ionic conductor hydrogel consisting of interpenetrating sodium carboxymethylcellulose (CMC) microsheets and polyacrylamide (PAAm) network. Intrinsic interactions between the CMC and PAAm endow the hydrogel with outstanding physical, mechanical robustness. The ionic hydrogel shows a very high transparency (98.2%), high adhesion efficiency (64% in strength), outstanding repeatability (500 cycles at the strain of 300%), sensitivity (Gauge factor = 3.15), and nearly real-time response (360 ms) to a small amount of stress. Additionally, two pieces of the semi-interpenetrating hydrogel can be bonded together with CMC membrane instantly without any external stimulation. Strain sensor based on the semi-interpenetrating network hydrogel has been demonstrated reliable in detecting a small strain caused by a subtle vibration up to a very large deformation by stretching. The hydrogel-based strain sensor may be applied in human motion detection, smart cushion and soft robotics.

Sensitivity boosts by the CPMAS CryoProbe for challenging biological assemblies

Despite breakthroughs in MAS NMR hardware and experimental methodologies, sensitivity remains a major challenge for large and complex biological systems. Here, we report that 3–4 fold higher sensitivities can be obtained in heteronuclear-detected experiments, using a novel HCN CPMAS probe, where the sample coil and the electronics operate at cryogenic temperatures, while the sample is maintained at ambient temperatures (BioSolids CryoProbe™). Such intensity enhancements permit recording 2D and 3D experiments that are otherwise time-prohibitive, such as 2D 15N-15N proton-driven spin diffusion and 15N-13C double cross polarization to natural abundance carbon experiments. The benefits of CPMAS CryoProbe-based experiments are illustrated for assemblies of kinesin Kif5b with microtubules, HIV-1 capsid protein assemblies, and fibrils of human Y145Stop and fungal HET-s prion proteins – demanding systems for conventional MAS solid-state NMR and excellent reference systems in terms of spectral quality. We envision that this probe technology will be beneficial for a wide range of applications, especially for biological systems suffering from low intrinsic sensitivity and at physiological temperatures.

The roles of silicon in combating cadmium challenge in the Marine diatom Phaeodactylum tricornutum

Marine phytoplankton possess a sophisticated homeostatic network to counteract metal toxicity. Changes in environmental conditions such as ambient nutrient concentrations can significantly impact their intrinsic metal sensitivity. In this study, we evaluated the role of silicon (Si) in counteracting cadmium (Cd) toxicity in the marine diatom Phaeodactylum tricornutum. We first demonstrated that Si enrichment dramatically enhanced Cd tolerance and changed the Cd accumulation in the diatom. Our modeling suggested that Si-enriched cells adsorbed more Cd but had a higher Cd elimination rate than the Si-starved cells. Examinations by atomic force microscopy and X-ray photoelectron spectroscopy revealed that the Si-enriched cells had better silification and more SiO− in the cell walls, which markedly lowered the surface potential of the diatom cells and allowed them to attract more Cd. Although the Si-enriched cells tended to have a high Cd burden when facing Cd stress, they suppressed the increase of intracellular Cd by both down-regulating the influx transporter ZIP and up-regulating the efflux transporter ATPase5-1B. Our study shows the significant roles Si plays in maintaining metal homeostasis and combating Cd challenge in marine diatoms.

Efficiency enhancement of pyridinium ylide dye-sensitized solar cells by introduction of benzothiadiazolyl chromophore: A computational study

Organic pyridinium ylide sensitizers NO108-NO111 with different anchoring groups show attractive applications in dye-sensitized solar cells. To elucidate the intrinsic sensitization mechanism of this series of dyes, theoretical calculations of electrochemical and spectroscopic properties for free and adsorbed ylides have been performed. Moreover, to prescreen and optimize suitable candidates for pyridinium ylide cells, the benzothiadiazole (BTD) group is introduced in the best-performing ylide NO111, and the afforded dye is coded as NO111-1. Comparing pyiridine-N-oxide in NO108, diethylmalonate in NO111 shows superior properties in terms of interfacial charge transfer, anti-aggregation, and long-term stability. It also demonstrates that the novel designed NO111-1-sensitized film possesses higher average theoretical maximum limit of short-circuit photocurrent density (JSCmax≈ 23 mA/cm2), and slower parasitic recombination than NO111 one. This result is expected to further reveal the effects of anchoring groups on properties of dyes, and is helpful for the design of more efficient pyridinium ylide dyes.

Improving and Stabilizing Perovskite Solar Cells with Incorporation of Graphene in the Spiro-OMeTAD Layer: Suppressed Li Ions Migration and Improved Charge Extraction

Perovskite solar cells (PSCs) have achieved a huge success in power conversion efficiency (PCE), although they still suffer from the long-term stability problem caused by the intrinsic sensitivity ...

Nanoparticle-Based Contrast Agents for 129Xe HyperCEST NMR and MRI Applications.

Spin hyperpolarization techniques have enabled important advancements in preclinical and clinical MRI applications to overcome the intrinsic low sensitivity of nuclear magnetic resonance. Functionalized xenon biosensors represent one of these approaches. They combine two amplification strategies, namely, spin exchange optical pumping (SEOP) and chemical exchange saturation transfer (CEST). The latter one requires host structures that reversibly bind the hyperpolarized noble gas. Different nanoparticle approaches have been implemented and have enabled molecular MRI with 129Xe at unprecedented sensitivity. This review gives an overview of the Xe biosensor concept, particularly how different nanoparticles address various critical aspects of gas binding and exchange, spectral dispersion for multiplexing, and targeted reporter delivery. As this concept is emerging into preclinical applications, comprehensive sensor design will be indispensable in translating the outstanding sensitivity potential into biomedical molecular imaging applications.