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At least 55 records · Page 3

Preliminary Assessment of Microwave Readout Multiplexing Factor

Ultra-high resolution microcalorimeter gamma spectroscopy is a new non-destructive assay technology for measurement of plutonium isotopic composition, with the potential to reduce total measurement uncertainty to a level competitive with destructive analysis methods [1-4]. Achieving this level of performance in practical applications requires not only the energy resolution now routinely achieved with transition-edge sensor microcalorimeter arrays (an order of magnitude better than for germanium detectors) but also high throughput. Microcalorimeter gamma spectrometers have not yet achieved detection efficiency and count rate capability that is comparable to germanium detectors, largely because of limits from existing readout technology. Microcalorimeter detectors must be operated at low temperature to achieve their exceptional energy resolution. Although the typical 100 mK operating temperatures can be achieved with reliable, cryogen-free systems, the cryogenic complexity and heat load from individual readout channels for large sensor arrays is prohibitive. Multiplexing is required for practical systems. The most mature multiplexing technology at present is time-division multiplexing (TDM) [3, 5-6]. In TDM, the sensor outputs are switched by applying bias current to one SQUID amplifier at a time. Transition-edge sensor (TES) microcalorimeter arrays as large as 256 pixels have been developed for X-ray and gamma-ray spectroscopy using TDM technology. Due to bandwidth limits and noise scaling, TDM is limited to a maximum multiplexing factor of approximately 32-40 sensors on one readout line [8]. Increasing the size of microcalorimeter arrays above the kilopixel scale, required to match the throughput of germanium detectors, requires the development of a new readout technology with a much higher multiplexing factor.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Four Channel Time Multiplexed Photonic Doppler Velocimetry using an Optical Switch

Photonic Doppler Velocimetry (PDV) is a diagnostic commonly used in shock physics and dynamic compression experiments to reliably get velocity information from experiments. In PDV systems, a common method of reducing experimental cost is to use time and frequency multiplexing to increase the number of PDV probes. With time multiplexing, interference between probes is a frequent problem. In this report, we look at using a high-speed optical switch to reduce this interference, including measuring the amount of interference generated to determine if it has the potential to affect experiments and integrating a time multiplexing system into an experiment. We find that, when applied to PDV systems, there is approximately (-23.4 ± 0.9) dB of interference measured in the short time Fourier transform between switch inputs. When an optical switch based time multiplexing system was integrated into a dynamic compression experiment, the system was able to successfully combine the signals from four different PDV probes onto a single optical cable without unacceptable levels of interference in the spectrogram. An optical switch based time multiplexing system appears to be a promising method for reducing the cost of fielding larger numbers of PDV probes in an experiment.

47 OTHER INSTRUMENTATION↗

High-speed multiplexing of keyboard data inputs

A high speed multiplexing system is described in which keyboard entered data is sequentially and automatically sampled by the multiplexing system for input to a computer. A sequencer is provided which sequentially and automatically controls the multiplexer to sample each keyboard input in accordance with a predetermined sampling sequence. Whenever keyboard entered data appears on input lines to the multiplexer, the system inputs the keyboard data to the computer during a brief time interval in which the multiplexer remains at the particular keyboard address or port. Thus, a high speed sampling circuit is provided whereby the only operator action required is data entry through a keyboard. Priority or interrupt systems are not required.

Anderson, T. O.↗

SQUID Multiplexers for Cryogenic Detector Arrays

SQUID multiplexers make it possible to build arrays of thousands of cryogenic detectors with a manageable number of readout channels. We are developing time-division SQUID multiplexers based on Nb trilayer SQUIDs to read arrays of superconducting transition-edge sensors. Our first-generation, 8-channel SQUID multiplexer was used in FIBRE, a one-dimensional TES array for submillimeter astronomy. Our second-generation 32-pixel multiplexer, based on an improved architecture, has been developed for instruments including Constellation-X, SCUBA-2, and solar x-ray astronomy missions. SCUBA-2, which is being developed for the James Clerk Maxwell Telescope, will have more than 10,000 pixels. We are now developing a third-generation architecture based on superconducting hot-electron switches. The use of SQUID multiplexers in instruments operating at above 2 K will also be discussed.

Irwin, Kent↗

Method and apparatus for multiplexing switch signals

Apparatus for multiplexing switch state signals comprises a plurality of switches and parallel weighted resistors connected in series between circuit ground and a node at a utilization device. The resistors are weighted as a function of a power of the same base, such as the power of the base 2, for coding the multiplexed switch state signals. A constant current source connected between the node and circuit ground drives current over a single cable conductor through the resistor. Each switch may be independently closed to change the switch state voltage signals multiplexed to the node. An analog-to-digital converter connected between the node and circuit ground demultiplexes the switch state signals received at the node and provides a switch state signal at each analog-to-digital output corresponding to the state of the switches at the moment. A potentiometer may replace a resistor and bypass switch combination in a position where the potentiometer has a maximum value of the lowest power of the base in order to multiplex a true analog voltage signal while switch state signals are unambiguously coded and multiplexed. The potentiometer in the least significant position permits the analog value to be in the range from 0 to a maximum corresponding to the least significant position of the switch state encoding. The invention may be used in redundancy systems by duplicating the invention with corresponding switches in each duplication ganged to open and close simultaneously upon operation of a pushbutton switch.

Hannaford, Blake↗

Indium Hybridization of Large Format TES Bolometer Arrays to Readout Multiplexers for Far-Infrared Astronomy

The advance of new detector technologies combined with enhanced fabrication methods has resulted in an increase in development of large format arrays. The next generation of scientific instruments will utilize detectors containing hundreds to thousands of elements providing a more efficient means to conduct large area sky surveys. Some notable detectors include a 32x32 x-ray microcalorimeter for Constellation-X, an infrared bolometer called SAFIRE to fly on the airborne observatory SOFIA, and the sub-millimeter bolometer SCUBA-2 to be deployed at the JCMT which will use more than 10,000 elements for two colors, each color using four 32x40 arrays. Of these detectors, SCUBA-2 is farthest along in development and uses indium hybridization to multiplexers for readout of the large number of elements, a technology that will be required to enable the next generation of large format arrays. Our current efforts in working toward large format arrays have produced GISMO, the Goddard IRAM Superconducting 2-Millimeter observer. GISMO is a far infrared instrument to be field tested later this year at the IRAM 30 meter telescope in Spain. GISMO utilizes transition edge sensor (TES) technology in an 8x16 filled array format that allows for typical fan-out wiring and wire-bonding to four 1x32 NIST multiplexers. GISMO'S electrical wiring is routed along the tops of 30 micron walls which also serve as the mechanical framework for the array. This architecture works well for the 128 element array, but is approaching the limit for routing the necessary wires along the surface while maintaining a high fill factor. Larger format arrays will benefit greatly from making electrical connections through the wafer to the backside, where they can be hybridized to a read-out substrate tailored to handling the wiring scheme. The next generation array we are developing is a 32x40 element array on a pitch of 1135 microns that conforms to the NIST multiplexer, already developed for the SCUBA-2 instrument This architecture will utilize electrical connections that route from the TES to the support frame and through the wafer. The detector chip will then be hybridized to the NIST multiplexer via indium bump bonding. In our development scheme we are using substrates that allow for diagnostic testing of electrical continuity across the entire array and we are testing our process to minimize or eliminate any contact resistance at metal interfaces. Our goal is hybridizing a fully functional 32x40 array of TES bolometers to a NIST multiplexer. The following work presents our current progress toward enabling this technology.

Miller, Timothy M.↗

A Review on Quantitative Multiplexed Proteomics

Over the last few decades, mass spectrometry-based proteomics has become an increasingly powerful tool that is now able to routinely detect and quantify thousands of proteins. A major advance for global protein quantification was the introduction of isobaric tags, which in a single experiment enable the global quantification of proteins across multiple samples. We refer to these methods as multiplexed proteomics. We discuss the principles, advantages, and drawbacks of various multiplexed proteomics techniques, and compare them to alternative approaches. We discuss how the emerging combination of multiplexing with targeted proteomics might enable the reliable and high-quality quantification of very low-abundance proteins across multiple conditions. We suggest that fusing multiplexed proteomics with data-independent acquisition approaches might enable the comparison of hundreds of different samples without missing values while maintaining the superb measurement precision and accuracy obtainable with isobaric tag quantification.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Transparent Dielectric Metasurfaces for Spatial Mode Multiplexing

Expanding the use of physical degrees of freedom to employ spatial multiplexing of data in optical communication is considered to be the most disruptive and effective solution for meeting the capacity demand of the growing information traffic. Development of space division–multiplexing methods stimulated research on spatial encoding, detection, and processing of data, attracting interest from various fields of science. Here a passive all–dielectric metasurface with near–unity transmission is demonstrated that engineers spatial mode profiles, potentially of an arbitrary complexity. The broadband response of the metasurface covers all S, C, and L bands of fiber communications. Unlike conventional phase plates, the metasurface allows for both phase and polarization conversion, providing full flexibility for the mode engineering. The dielectric metasurface is employed for mode multiplexing in a free–space optical communication system with an extinction ratio in excess of 20 dB over the whole C–band with negligible penalty even for 100 Gb s –1 data transmission. Furthermore, these results merge two seemingly different fields, optical communication and metamaterials , and they suggest a novel approach for an ultimate miniaturization of mode multiplexers and advanced LiFi technologies.

97 MATHEMATICS AND COMPUTING↗

Results and Limits of Time-Division Multiplexing for the BICEP Array High-Frequency Receivers

Time-division multiplexing is the readout architecture of choice for many ground and space experiments, as it is a very mature technology with proven outstanding low-frequency noise stability, which represents a central challenge in multiplexing. Once fully populated, each of the two BICEP Array high-frequency receivers, observing at 150 GHz and 220/270 GHz, will have 7776 TES detectors tiled on the focal plane. The constraints set by these two receivers required a redesign of the warm readout electronics. The new version of the standard multichannel electronics, developed and built at the University of British Columbia, is presented here for the first time. BICEP Array operates time-division multiplexing readout technology to the limits of its capabilities in terms of multiplexing rate, noise and cross talk, and applies them in rigorously demanding scientific application requiring extreme noise performance and systematic error control. Finally, future experiments like CMB-S4 plan to use TES bolometers with time-division/SQUID-based readout for an even larger number of detectors.

47 OTHER INSTRUMENTATION↗

NaroNet: Discovery of tumor microenvironment elements from highly multiplexed images

Understanding the spatial interactions between the elements of the tumor microenvironment -i.e. tumor cells. fibroblasts, immune cells- and how these interactions relate to the diagnosis or prognosis of a tumor is one of the goals of computational pathology. We present NaroNet, a deep learning framework that models the multi-scale tumor microenvironment from multiplex-stained cancer tissue images and provides patient-level interpretable predictions using a seamless end-to-end learning pipeline. Trained only with multiplex-stained tissue images and their corresponding patient-level clinical labels, NaroNet unsupervisedly learns which cell phenotypes, cell neighborhoods, and neighborhood interactions have the highest influence to predict the correct label. To this end, NaroNet incorporates several novel and state-of-the-art deep learning techniques, such as patch-level contrastive learning, multi-level graph embeddings, a novel max-sum pooling operation, or a metric that quantifies the relevance that each microenvironment element has in the individual predictions. We validate NaroNet using synthetic data simulating multiplex-immunostained images where a patient label is artificially associated to the -adjustable- probabilistic incidence of different microenvironment elements. We then apply our model to two sets of images of human cancer tissues: 336 seven-color multiplex-immunostained images from 12 high-grade endometrial cancer patients; and 382 35-plex mass cytometry images from 215 breast cancer patients. In both synthetic and real datasets, NaroNet provides outstanding predictions of relevant clinical information while associating those predictions to the presence of specific microenvironment elements.

60 APPLIED LIFE SCIENCES↗

TMTpro Complementary Ion Quantification Increases Plexing and Sensitivity for Accurate Multiplexed Proteomics at the MS2 Level

Multiplexed proteomics is a powerful tool to assay cell states in health and disease, but accurate quantification of relative protein changes is impaired by interference from co-isolated peptides. Most widely, this issue is alleviated by MS3-based quantification, reducing sensitivity and requiring specialized instrumentation. An alternative approach is quantification by complementary ions, which allows accurate and precise multiplexed quantification at the MS2 level and is compatible with the most widely distributed instruments. However, complementary ions of the popular TMT tag form inefficiently and plexing is limited to five channels. In this work, we evaluate and optimize complementary ion quantification for the recently released TMTPro tag, which increases plexing capacity to 8 channels (TMTProC). We find that the beneficial fragmentation properties increase quantification signal five-fold compared to TMT. This increased sensitivity results in ~50% more proteins quantified compared to TMTPro-MS3 and even slightly outperforms TMTPro-MS2. Furthermore, TMTProC quantification is more accurate than TMTPro-MS2 and even superior to TMTPro-MS3. To demonstrate the power of TMTProC, we analyzed a human and yeast interference sample and were able to quantify 13,290 proteins in 24 fractions. Thus, TMTProC advances multiplexed proteomics data quality and widens access to accurate multiplexed proteomics beyond laboratories with MS3-capable instrumentation.

59 BASIC BIOLOGICAL SCIENCES↗

Demonstration of a 1820 channel multiplexer for transition-edge sensor bolometers

The scalability of most transition-edge sensor arrays is limited by the multiplexing technology, which combines their signals over a reduced number of wires and amplifiers. Here, in this Letter, we present and demonstrate a multiplexer design optimized for transition-edge sensor bolometers with 1820 sensors per readout unit, a factor of two more than the previous state-of-the-art. The design is optimized for cosmic microwave background imaging applications, and it builds on previous microwave superconducting quantum interference device multiplexers by doubling the available readout bandwidth to the full 4–8 GHz octave. Evaluating the key performance metrics of yield, sensitivity, and crosstalk through laboratory testing, we find an end-to-end operable detector yield of 78%, a typical nearest-neighbor crosstalk amplitude of ∼0.4%, and a median white noise level of 83 pA/$\sqrt{\textrm{Hz}}$ due to the multiplexer, corresponding to an estimated contribution of 4% to the total system noise for a ground-based cosmic microwave background telescope. Additionally, we identify a possible path toward reducing resonator loss for future designs with reduced noise. We expect these developments to alleviate the system complexity, cryogenic requirements, and cost of future large arrays of low temperature detectors.

cosmic microwave background↗

Simultaneous multiplexed materials characterization using a high-precision hard X-ray micro-slit array

Here, the needs both for increased experimental throughput and for in operando characterization of functional materials under increasingly realistic experimental conditions have emerged as major challenges across the whole of crystallography. A novel measurement scheme that allows multiplexed simultaneous measurements from multiple nearby sample volumes is presented. This new approach enables better measurement statistics or direct probing of heterogeneous structure, dynamics or elemental composition. To illustrate, the submicrometer precision that optical lithography provides has been exploited to create a multiplexed form of ultra-small-angle scattering based X-ray photon correlation spectroscopy (USAXS-XPCS) using micro-slit arrays fabricated by photolithography. Multiplexed USAXS-XPCS is applied to follow the equilibrium dynamics of a simple colloidal suspension. While the dependence of the relaxation time on momentum transfer, and its relationship with the diffusion constant and the static structure factor, follow previous findings, this measurements-in-parallel approach reduces the statistical uncertainties of this photon-starved technique to below those associated with the instrument resolution. More importantly, we note the potential of the multiplexed scheme to elucidate the response of different components of a heterogeneous sample under identical experimental conditions in simultaneous measurements. Lastly, in the context of the X-ray synchrotron community, this scheme is, in principle, applicable to all in-line synchrotron techniques. Indeed, it has the potential to open a new paradigm for in operando characterization of heterogeneous functional materials, a situation that will be even further enhanced by the ongoing development of multi-bend achromat storage ring designs as the next evolution of large-scale X-ray synchrotron facilities around the world.

36 MATERIALS SCIENCE↗

Development of ROACH firmware for microwave multiplexed X-ray TES microcalorimeters

We are developing room temperature electronics based upon the ROACH platform for reading out microwave multiplexed X-ray TES. ROACH is an open-source hardware and software platform featuring a large Xilinx Field Programmable Gate Array (FPGA), Power PC processor, several 10GB Ethernet SFP+ interfaces, and a collection of daughter boards for analog signal generation and acquisition. The combination of a ROACH board, ADC/DAC conversion daughter boards, and hardware for RF mixing allows for the generation and capture of multiple RF tones for reading out microwave multiplexed x-ray TES microcalorimeters. The FPGA is used to generate multiple tones in base band, from 10MHz to 250MHz, which are subsequently mixed to RF in the multiple GHz range and sent through the microwave multiplexer. The tones are generated in the FPGA by storing a large lookup table in Quad Data Rate (QDR) SRAM modules and playing out the waveform to a DAC board. Once the signal has been modulated to RF, passed through the microwave multiplexer, and has been modulated back to base band, the signal is digitized by an ADC board. The tones are modulated to 0Hz by using a FPGA circuit consisting of a polyphase filter bank, several Xilinx FFT blocks, Xilinx CORDIC blocks (for converting to magnitude and phase), and special phase accumulator circuit for mixing to exactly 0Hz. Upwards of 256 channels can be simultaneously captured and written into a bank of 256 First-In-First-Out (FIFO) memories, with each FIFO corresponding to a channel. Individual channel data can be further processed in the FPGA before being streamed through a 10GB Ethernet fiber-optic interface to a Linux system. The Linux system runs software written in Python and QT C++ for controlling the ROACH system, capturing data, and processing data.

Firmware↗

Turbo‐charging crop improvement: harnessing multiplex editing for polygenic trait engineering and beyond

Multiplex CRISPR editing has emerged as a transformative platform for plant genome engineering, enabling the simultaneous targeting of multiple genes, regulatory elements, or chromosomal regions. This approach is effective for dissecting gene family functions, addressing genetic redundancy, engineering polygenic traits, and accelerating trait stacking and de novo domestication. Its applications now extend beyond standard gene knockouts to include epigenetic and transcriptional regulation, chromosomal engineering, and transgene‐free editing. These capabilities are advancing crop improvement not only in annual species but also in more complex systems such as polyploids, undomesticated wild relatives, and species with long generation times. At the same time, multiplex editing presents technical challenges, including complex construct design and the need for robust, scalable mutation detection. We discuss current toolkits and recent innovations in vector architecture, such as promoter and scaffold engineering, that streamline workflows and enhance editing efficiency. High‐throughput sequencing technologies, including long‐read platforms, are improving the resolution of complex editing outcomes such as structural rearrangements—often missed by standard genotyping—when targeting repetitive or tandemly spaced loci. To fully realize the potential of multiplex genome engineering, there is growing demand for user‐friendly, synthetic biology‐compatible, and scalable computational workflows for gRNA design, construct assembly, and mutation analysis. Experimentally validated inducible or tissue‐specific promoters are also highly desirable for achieving spatiotemporal control. As these tools continue to evolve, multiplex CRISPR editing is poised to become a foundational technology of next‐generation crop improvement to address challenges in agriculture, sustainability, and climate resilience.

59 BASIC BIOLOGICAL SCIENCES↗

Multiplexed Post-Experimental Monoisotopic Mass Refinement ( m PE-MMR) to Increase Sensitivity and Accuracy in Peptide Identifications from Tandem Mass Spectra of Cofragmentation

Mass spectrometry (MS)-based proteomics, which uses high-resolution hybrid mass spectrometers such as the quadrupole-orbitrap mass spectrometer, can yield tens of thousands of tandem mass (MS/MS) spectra of high resolution during a routine bottom-up experiment. Despite being a fundamental and key step in MS-based proteomics, the accurate determination and assignment of precursor monoisotopic masses to the MS/MS spectra remains difficult. The difficulties stem from imperfect isotopic envelopes of precursor ions, inaccurate charge states for precursor ions, and cofragmentation. We describe a composite method of utilizing MS data to assign accurate monoisotopic masses to MS/MS spectra, including those subject to cofragmentation. The method, “multiplexed post-experiment monoisotopic mass refinement” (mPE-MMR), consists of the following: multiplexing of precursor masses to assign multiple monoisotopic masses of cofragmented peptides to the corresponding multiplexed MS/MS spectra, multiplexing of charge states to assign correct charges to the precursor ions of MS/ MS spectra with no charge information, and mass correction for inaccurate monoisotopic peak picking. When combined with MS-GF+, a database search algorithm based on fragment mass difference, mPE-MMR effectively increases both sensitivity and accuracy in peptide identification from complex high-throughput proteomics data compared to conventional methods.

Environmental Molecular Sciences Laboratory↗

Singleplex, multiplex and pooled sample real-time RT-PCR assays for detection of SARS-CoV-2 in an occupational medicine setting

Abstract For workplaces which cannot operate as telework or remotely, there is a critical need for routine occupational SARS-CoV-2 diagnostic testing. Although diagnostic tests including the CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel (CDC Diagnostic Panel) (EUA200001) were made available early in the pandemic, resource scarcity and high demand for reagents and equipment necessitated priority of symptomatic patients. There is a clearly defined need for flexible testing methodologies and strategies with rapid turnaround of results for (1) symptomatic, (2) asymptomatic with high-risk exposures and (3) asymptomatic populations without preexisting conditions for routine screening to address the needs of an on-site work force. We developed a distinct SARS-CoV-2 diagnostic assay based on the original CDC Diagnostic Panel (EUA200001), yet, with minimum overlap for currently employed reagents to eliminate direct competition for limited resources. As the pandemic progressed with testing loads increasing, we modified the assay to include 5-sample pooling and amplicon target multiplexing. Analytical sensitivity of the pooled and multiplexed assays was rigorously tested with contrived positive samples in realistic patient backgrounds. Assay performance was determined with clinical samples previously assessed with an FDA authorized assay. Throughout the pandemic we successfully tested symptomatic, known contact and travelers within our occupational population with a ~ 24–48-h turnaround time to limit the spread of COVID-19 in the workplace. Our singleplex assay had a detection limit of 31.25 copies per reaction. The three-color multiplexed assay maintained similar sensitivity to the singleplex assay, while tripling the throughput. The pooling assay further increased the throughput to five-fold the singleplex assay, albeit with a subtle loss of sensitivity. We subsequently developed a hybrid ‘multiplex-pooled’ strategy to testing to address the need for both rapid analysis of samples from personnel at high risk of COVID infection and routine screening. Herein, our SARS-CoV-2 assays specifically address the needs of occupational healthcare for both rapid analysis of personnel at high-risk of infection and routine screening that is essential for controlling COVID-19 disease transmission. In addition to SARS-CoV-2 and COVID-19, this work demonstrates successful flexible assays developments and deployments with implications for emerging highly transmissible diseases and future pandemics.

60 APPLIED LIFE SCIENCES↗

Frequency multiplexing for readout of spin qubits

We demonstrate a low loss, chip-level frequency multiplexing scheme for readout of scaled-up spin qubit devices. By integrating separate bias tees and resonator circuits on-chip for each readout channel, we realise dispersive gate-sensing in combination with charge detection based on two radio frequency quantum point contacts. We apply this approach to perform multiplexed readout of a double quantum dot in the few-electron regime and further demonstrate operation of a 10-channel multiplexing device. Limitations for scaling spin qubit readout to large numbers of multiplexed channels are discussed.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗