Impact of Prosigna test on adjuvant treatment decision in lymph node-negative early breast cancer-a prospective national multicentre study (EMIT-1).

BACKGROUND: EMIT-1 is a national, observational, single-arm trial designed to assess the value of the Prosigna, Prediction Analysis of Microarray using the 50 gene classifier (PAM50)/Risk of Recurrence (ROR), test as a routine diagnostic tool, examining its impact on adjuvant treatment decisions, clinical outcomes, side-effects and cost-effectiveness. Here we present the impact on treatment decisions. PATIENTS AND METHODS: Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative pT1-pT2 lymph node-negative early breast cancer (EBC) were included. The Prosigna test and standard histopathology assessments were carried out. Clinicians' treatment decisions were recorded before (pre-Prosigna) and after (post-Prosigna) the Prosigna test results were disclosed. RESULTS: Of 2217 patients included, 2178 had conclusive Prosigna results. The pre-Prosigna treatment decisions were: no systemic treatment (NT) in 27% of patients, endocrine treatment alone (ET) in 38% and chemotherapy (CT) followed by ET (CT + ET) in 35%. Post-Prosigna treatment decisions were 25% NT, 51% ET and 24% CT + ET, respectively. Adjuvant treatment changed in 28% of patients, including 21% change in CT use. Among patients assigned to CT + ET pre-Prosigna, 45% were de-escalated to ET post-Prosigna. Of patients assigned to ET, 12% were escalated to CT + ET and 8% were de-escalated to NT; of those assigned to NT, 18% were escalated to ET/CT + ET. CT was more frequently recommended for patients aged ≤50 years. In the subgroup with pT1c-pT2 G2 and intermediate Ki67 (0.5-1.5× local laboratory median Ki67 score), the pre-Prosigna CT treatment decision varied widely across hospitals (3%-51%). Post-Prosigna, the variability of CT use was markedly reduced (8%-24%). The correlation between Ki67 and ROR score within this subgroup was poor (r = 0.25-0.39). The median ROR score increased by increasing histological grade, but the ROR score ranges were wide (for G1 0-79, G2 0-90, G3 16-94). CONCLUSION: The Prosigna test result changed adjuvant treatment decisions in all EBC clinical risk groups, markedly decreased the CT use for patients categorized as higher clinical risk pre-Prosigna and reduced treatment decision discrepancies between hospitals.

Joule spectroscopy of hybrid superconductor-semiconductor nanodevices.

Hybrid superconductor-semiconductor devices offer highly tunable platforms, potentially suitable for quantum technology applications, that have been intensively studied in the past decade. Here we establish that measurements of the superconductor-to-normal transition originating from Joule heating provide a powerful spectroscopical tool to characterize such hybrid devices. Concretely, we apply this technique to junctions in full-shell Al-InAs nanowires in the Little-Parks regime and obtain detailed information of each lead independently and in a single measurement, including differences in the superconducting coherence lengths of the leads, inhomogeneous covering of the epitaxial shell, and the inverse superconducting proximity effect; all-in-all constituting a unique fingerprint of each device with applications in the interpretation of low-bias data, the optimization of device geometries, and the uncovering of disorder in these systems. Besides the practical uses, our work also underscores the importance of heating in hybrid devices, an effect that is often overlooked.

Effect of in-plane alignment on selective area grown homo-epitaxial nanowires.

In-plane selective area growth (SAG) of III-V nanowires (NWs) has emerged as a scalable materials platform for quantum electronics and photonics applications. Most applications impose strict requirements on the material characteristics which makes optimization of the crystal quality vital. Alignment of in-plane SAG NWs with respect to the substrate symmetry is of importance due to the large substrate-NW interface as well as to obtain nanostructures with well-defined facets. Understanding the role of mis-orientation is thus important for designing devices and interpretation of electrical performance of devices. Here we study the effect of mis-orientation on morphology of selectively grown NWs oriented along the [1 1̅ 1̅] direction on GaAs(2 1 1)B. Atomic force microscopy is performed to extract facet roughness as a measure of structural quality. Further, we evaluate the dependence of material incorporation in NWs on the orientation and present the facet evolution in between two high symmetry in-plane orientations. By investigating the length dependence of NW morphology, we find that the morphology of ≈1µm long nominally aligned NWs remains unaffected by the unintentional misalignment associated with the processing and alignment of the sample under study. Finally, we show that using Sb as a surfactant during growth improves root-mean-square facet roughness for large misalignment but does not lower it for nominally aligned NWs.

Microwave Susceptibility Observation of Interacting Many-Body Andreev States.

Electrostatic charging affects the many-body spectrum of Andreev states, yet its influence on their microwave properties has not been elucidated. We developed a circuit quantum electrodynamics probe that, in addition to transition spectroscopy, measures the microwave susceptibility of different states of a semiconductor nanowire weak link with a single dominant (spin-degenerate) Andreev level. We found that the microwave susceptibility does not exhibit a particle-hole symmetry, which we qualitatively explain as an influence of Coulomb interaction. Moreover, our state-selective measurement reveals a large, π-phase shifted contribution to the response common to all many-body states which can be interpreted as arising from a phase-dependent continuum in the superconducting density of states.

Signatures of Interactions in the Andreev Spectrum of Nanowire Josephson Junctions.

We performed microwave spectroscopy of an InAs nanowire between superconducting contacts implementing a finite-length, multichannel Josephson weak link. Certain features in the spectra, such as the splitting by spin-orbit interactions of the transition lines among Andreev states, have been already understood in terms of noninteracting models. However, we identify here additional transitions, which evidence the presence of Coulomb interactions. By combining experimental measurements and model calculations, we reach a qualitative understanding of these very rich Andreev spectra.

Integrated bioelectronic proton-gated logic elements utilizing nanoscale patterned Nafion.

A central endeavour in bioelectronics is the development of logic elements to transduce and process ionic to electronic signals. Motivated by this challenge, we report fully monolithic, nanoscale logic elements featuring n- and p-type nanowires as electronic channels that are proton-gated by electron-beam patterned Nafion. We demonstrate inverter circuits with state-of-the-art ion-to-electron transduction performance giving DC gain exceeding 5 and frequency response up to 2 kHz. A key innovation facilitating the logic integration is a new electron-beam process for patterning Nafion with linewidths down to 125 nm. This process delivers feature sizes compatible with low voltage, fast switching elements. This expands the scope for Nafion as a versatile patternable high-proton-conductivity element for bioelectronics and other applications requiring nanoengineered protonic membranes and electrodes.

Coherent manipulation of an Andreev spin qubit.

Two promising architectures for solid-state quantum information processing are based on electron spins electrostatically confined in semiconductor quantum dots and the collective electrodynamic modes of superconducting circuits. Superconducting electrodynamic qubits involve macroscopic numbers of electrons and offer the advantage of larger coupling, whereas semiconductor spin qubits involve individual electrons trapped in microscopic volumes but are more difficult to link. We combined beneficial aspects of both platforms in the Andreev spin qubit: the spin degree of freedom of an electronic quasiparticle trapped in the supercurrent-carrying Andreev levels of a Josephson semiconductor nanowire. We performed coherent spin manipulation by combining single-shot circuit-quantum-electrodynamics readout and spin-flipping Raman transitions and found a spin-flip time T S = 17 microseconds and a spin coherence time T 2E = 52 nanoseconds. These results herald a regime of supercurrent-mediated coherent spin-photon coupling at the single-quantum level.

Direct Microwave Measurement of Andreev-Bound-State Dynamics in a Semiconductor-Nanowire Josephson Junction.

The modern understanding of the Josephson effect in mesosopic devices derives from the physics of Andreev bound states, fermionic modes that are localized in a superconducting weak link. Recently, Josephson junctions constructed using semiconducting nanowires have led to the realization of superconducting qubits with gate-tunable Josephson energies. We have used a microwave circuit QED architecture to detect Andreev bound states in such a gate-tunable junction based on an aluminum-proximitized indium arsenide nanowire. We demonstrate coherent manipulation of these bound states, and track the bound-state fermion parity in real time. Individual parity-switching events due to nonequilibrium quasiparticles are observed with a characteristic timescale T_{parity}=160±10 µs. The T_{parity} of a topological nanowire junction sets a lower bound on the bandwidth required for control of Majorana bound states.

Effective g Factor of Subgap States in Hybrid Nanowires.

We use the effective g factor of Andreev subgap states in an axial magnetic field to investigate how the superconducting density of states is distributed between the semiconductor core and the superconducting shell in hybrid nanowires. We find a steplike reduction of the Andreev g factor and an improved hard gap with reduced carrier density in the nanowire, controlled by gate voltage. These observations are relevant for Majorana devices, which require tunable carrier density and a g factor exceeding that of the parent superconductor.

p-GaAs Nanowire Metal-Semiconductor Field-Effect Transistors with Near-Thermal Limit Gating.

Difficulties in obtaining high-performance p-type transistors and gate insulator charge-trapping effects present two major challenges for III-V complementary metal-oxide semiconductor (CMOS) electronics. We report a p-GaAs nanowire metal-semiconductor field-effect transistor (MESFET) that eliminates the need for a gate insulator by exploiting the Schottky barrier at the metal-GaAs interface. Our device beats the best-performing p-GaSb nanowire metal-oxide-semiconductor field effect transistor (MOSFET), giving a typical subthreshold swing of 62 mV/dec, within 4% of the thermal limit, on-off ratio ∼105, on-resistance ∼700 kΩ, contact resistance ∼30 kΩ, peak transconductance 1.2 µS/µm, and high-fidelity ac operation at frequencies up to 10 kHz. The device consists of a GaAs nanowire with an undoped core and heavily Be-doped shell. We carefully etch back the nanowire at the gate locations to obtain Schottky-barrier insulated gates while leaving the doped shell intact at the contacts to obtain low contact resistance. Our device opens a path to all-GaAs nanowire MESFET complementary circuits with simplified fabrication and improved performance.

Yu-Shiba-Rusinov screening of spins in double quantum dots.

A magnetic impurity coupled to a superconductor gives rise to a Yu-Shiba-Rusinov (YSR) state inside the superconducting energy gap. With increasing exchange coupling the excitation energy of this state eventually crosses zero and the system switches to a YSR ground state with bound quasiparticles screening the impurity spin by h/2. Here we explore indium arsenide (InAs) nanowire double quantum dots tunnel coupled to a superconductor and demonstrate YSR screening of spin-1/2 and spin-1 states. Gating the double dot through nine different charge states, we show that the honeycomb pattern of zero-bias conductance peaks, archetypal of double dots coupled to normal leads, is replaced by lines of zero-energy YSR states. These enclose regions of YSR-screened dot spins displaying distinctive spectral features, and their characteristic shape and topology change markedly with tunnel coupling strengths. We find excellent agreement with a simple zero-bandwidth approximation, and with numerical renormalization group calculations for the two-orbital Anderson model.

Evolution of Nanowire Transmon Qubits and Their Coherence in a Magnetic Field.

We present an experimental study of flux- and gate-tunable nanowire transmons with state-of-the-art relaxation time allowing quantitative extraction of flux and charge noise coupling to the Josephson energy. We evidence coherence sweet spots for charge, tuned by voltage on a proximal side gate, where first order sensitivity to switching two-level systems and background 1/f noise is minimized. Next, we investigate the evolution of a nanowire transmon in a parallel magnetic field up to 70 mT, the upper bound set by the closing of the induced gap. Several features observed in the field dependence of qubit energy relaxation and dephasing times are not fully understood. Using nanowires with a thinner, partially covering Al shell will enable operation of these circuits up to 0.5 T, a regime relevant for topological quantum computation and other applications.

Supercurrent in a Double Quantum Dot.

We demonstrate the Josephson effect in a serial double quantum dot defined in a nanowire with epitaxial superconducting leads. The supercurrent stability diagram adopts a honeycomb pattern. We observe sharp discontinuities in the magnitude of the critical current, I_{c}, as a function of dot occupation, related to doublet to singlet ground state transitions. Detuning of the energy levels offers a tuning knob for I_{c}, which attains a maximum at zero detuning. The consistency between experiment and theory indicates that our device is a faithful realization of the two-impurity Anderson model.

Transport Signatures of Quasiparticle Poisoning in a Majorana Island.

We investigate effects of quasiparticle poisoning in a Majorana island with strong tunnel coupling to normal-metal leads. In addition to the main Coulomb blockade diamonds, "shadow" diamonds appear, shifted by 1e in gate voltage, consistent with transport through an excited (poisoned) state of the island. Comparison to a simple model yields an estimate of parity lifetime for the strongly coupled island (∼1 µs) and sets a bound for a weakly coupled island (>10 µs). Fluctuations in the gate-voltage spacing of Coulomb peaks at high field, reflecting Majorana hybridization, are enhanced by the reduced lever arm at strong coupling. When converted from gate voltage to energy units, fluctuations are consistent with previous measurements.

Towards low-dimensional hole systems in Be-doped GaAs nanowires.

GaAs was central to the development of quantum devices but is rarely used for nanowire-based quantum devices with InAs, InSb and SiGe instead taking the leading role. p-type GaAs nanowires offer a path to studying strongly confined 0D and 1D hole systems with strong spin-orbit effects, motivating our development of nanowire transistors featuring Be-doped p-type GaAs nanowires, AuBe alloy contacts and patterned local gate electrodes towards making nanowire-based quantum hole devices. We report on nanowire transistors with traditional substrate back-gates and EBL-defined metal/oxide top-gates produced using GaAs nanowires with three different Be-doping densities and various AuBe contact processing recipes. We show that contact annealing only brings small improvements for the moderately doped devices under conditions of lower anneal temperature and short anneal time. We only obtain good transistor performance for moderate doping, with conduction freezing out at low temperature for lowly doped nanowires and inability to reach a clear off-state under gating for the highly doped nanowires. Our best devices give on-state conductivity 95 nS, off-state conductivity 2 pS, on-off ratio [Formula: see text], and sub-threshold slope 50 mV/dec at [Formula: see text] K. Lastly, we made a device featuring a moderately doped nanowire with annealed contacts and multiple top-gates. Top-gate sweeps show a plateau in the sub-threshold region that is reproducible in separate cool-downs and indicative of possible conductance quantisation highlighting the potential for future quantum device studies in this material system.

Hybrid Nanowire Ion-to-Electron Transducers for Integrated Bioelectronic Circuitry.

A key task in the emerging field of bioelectronics is the transduction between ionic/protonic and electronic signals at high fidelity. This is a considerable challenge since the two carrier types exhibit intrinsically different physics and are best supported by very different materials types-electronic signals in inorganic semiconductors and ionic/protonic signals in organic or bio-organic polymers, gels, or electrolytes. Here we demonstrate a new class of organic-inorganic transducing interface featuring semiconducting nanowires electrostatically gated using a solid proton-transporting hygroscopic polymer. This model platform allows us to study the basic transducing mechanisms as well as deliver high fidelity signal conversion by tapping into and drawing together the best candidates from traditionally disparate realms of electronic materials research. By combining complementary n- and p-type transducers we demonstrate functional logic with significant potential for scaling toward high-density integrated bioelectronic circuitry.

Normal, superconducting and topological regimes of hybrid double quantum dots.

Epitaxial semiconductor-superconductor hybrid materials are an excellent basis for studying mesoscopic and topological superconductivity, as the semiconductor inherits a hard superconducting gap while retaining tunable carrier density. Here, we investigate double-quantum-dot structures made from InAs nanowires with a patterned epitaxial Al two-facet shell that proximitizes two gate-defined segments along the nanowire. We follow the evolution of mesoscopic superconductivity and charging energy in this system as a function of magnetic field and voltage-tuned barriers. Interdot coupling is varied from strong to weak using side gates, and the ground state is varied between normal, superconducting and topological regimes by applying a magnetic field. We identify the topological transition by tracking the spacing between successive co-tunnelling peaks as a function of axial magnetic field and show that the individual dots host weakly hybridized Majorana modes.

Majorana bound state in a coupled quantum-dot hybrid-nanowire system.

Hybrid nanowires combining semiconductor and superconductor materials appear well suited for the creation, detection, and control of Majorana bound states (MBSs). We demonstrate the emergence of MBSs from coalescing Andreev bound states (ABSs) in a hybrid InAs nanowire with epitaxial Al, using a quantum dot at the end of the nanowire as a spectrometer. Electrostatic gating tuned the nanowire density to a regime of one or a few ABSs. In an applied axial magnetic field, a topological phase emerges in which ABSs move to zero energy and remain there, forming MBSs. We observed hybridization of the MBS with the end-dot bound state, which is in agreement with a numerical model. The ABS/MBS spectra provide parameters that are useful for understanding topological superconductivity in this system.

Wet etch methods for InAs nanowire patterning and self-aligned electrical contacts.

Advanced synthesis of semiconductor nanowires (NWs) enables their application in diverse fields, notably in chemical and electrical sensing, photovoltaics, or quantum electronic devices. In particular, indium arsenide (InAs) NWs are an ideal platform for quantum devices, e.g. they may host topological Majorana states. While the synthesis has been continously perfected, only a few techniques have been developed to tailor individual NWs after growth. Here we present three wet chemical etch methods for the post-growth morphological engineering of InAs NWs on the sub-100 nm scale. The first two methods allow the formation of self-aligned electrical contacts to etched NWs, while the third method results in conical shaped NW profiles ideal for creating smooth electrical potential gradients and shallow barriers. Low temperature experiments show that NWs with etched segments have stable transport characteristics and can serve as building blocks of quantum electronic devices. As an example we report the formation of a single electrically stable quantum dot between two etched NW segments.

Gatemon Benchmarking and Two-Qubit Operations.

Recent experiments have demonstrated superconducting transmon qubits with semiconductor nanowire Josephson junctions. These hybrid gatemon qubits utilize field effect tunability characteristic of semiconductors to allow complete qubit control using gate voltages, potentially a technological advantage over conventional flux-controlled transmons. Here, we present experiments with a two-qubit gatemon circuit. We characterize qubit coherence and stability and use randomized benchmarking to demonstrate single-qubit gate errors below 0.7% for all gates, including voltage-controlled Z rotations. We show coherent capacitive coupling between two gatemons and coherent swap operations. Finally, we perform a two-qubit controlled-phase gate with an estimated fidelity of 91%, demonstrating the potential of gatemon qubits for building scalable quantum processors.