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Current rate of data generation and the need for real‐time data analytics can benefit from new computational approaches where computation proceeds in a massively parallel way while being scalable and energy efficient. Biological systems arising from interaction of living cells can provide such pathways for sustainable computing. Current designs for biocomputing leveraging the information processing units of the cells, such as DNA, gene, or protein circuitries, are inherently slow (hours to days speed) and, therefore, are primarily being considered for archival storage of information. On the contrary, electrically active cells that can synchronize in milliseconds and can be connected as networks to perform massively parallel tasks can transform biocomputing and lead to novel ways of high throughput information processing. Herein, coupled oscillator networks made of living cardiac muscle cells, or bio‐oscillators, is explored as collective computing components for solving computationally hard problems. An empirically validated circuit compatible macromodel is developed for the bio‐oscillators and the fibroblast cells acting as coupling elements, to faithfully reproduce the synchronization dynamics of the network and it is shown that such bio‐oscillator network can be scaled up to hundreds of nodes and be used to solve computationally hard problems faster than traditional heuristics‐based Boolean algorithms.

8534 Background: The current standard of care for patients with inoperable stage III non-small cell lung cancer (NSCLC) includes chemoradiation (CRT) followed by up to 1 year of checkpoint inhibitor (CPI) therapy. However, many patients are not able to complete 1 year of treatment and the optimal duration of consolidation therapy remains unknown. Identifying minimal residual disease (MRD) via detection of circulating tumor DNA (ctDNA) may help inform the optimal duration of treatment. Here we report the results of a preplanned correlative study evaluating the association between detectable ctDNA and survival outcomes from the BTCRC LUN 16-081 phase 2 trial of consolidation nivolumab or nivolumab plus ipilimumab following CRT in patients with unresectable Stage III NSCLC (NCT03285321). Methods: Following CRT, patients with unresectable stage IIIA/B NSCLC were randomized 1:1 to receive nivolumab 480 mg IV Q4weeks for up to 6 cycles or nivolumab 240 mg IV Q2weeks plus ipilimumab 1 mg/kg IV Q6weeks for up to 4 cycles. Plasma samples for ctDNA analysis were collected after completion of CRT, prior to C2D1 of CPI, and at the end of treatment or withdrawal from the study. Tumor genotyping and ctDNA analysis were performed using CAPP-Seq with a panel targeting 260 genes recurrently mutated in NSCLC. Patient-specific tumor variants were identified using tumor tissue or baseline plasma and matched leukocyte DNA samples. Tumor variants were then monitored in plasma samples using a tumor mutation-informed bioinformatic strategy. Results: Thirty-nine patients received either nivolumab (n = 25; cycles: median = 6, range 1-6), or nivolumab plus ipilimumab (n = 14; cycles; median = 2, range = 1-6). Patients with detectable ctDNA MRD after completion of CRT demonstrated significantly inferior progression free survival (PFS) than patients who were MRD-negative (12-month 29% vs 76%, 24-month 29% vs 68%, P = 0.003), prior to C2D1 of CPI (12-month 0% vs 85%, 24-month 0% vs 72%, P < 0.0001) and at the end of CPI (12-month 14% vs 90%, 24-month 14% vs 79%, P < 0.0001). Patients with undetectable ctDNA MRD at the end of CPI (median cycles = 5.5; range 1-6) demonstrated 24-month overall survival of 91%. Additionally, patients with decreasing or undetectable ctDNA levels after one cycle of CPI had improved outcomes compared to patients with increasing ctDNA levels (24-month PFS 73% vs 0%, P < 0.0001). Progression of disease occurred within 10.8 months of starting CPI in all patients with increasing ctDNA levels at C2D1. Conclusions: Detectable ctDNA before, during, and after consolidation CPI is strongly associated with inferior survival outcomes. Furthermore, less than 12 months of CPI consolidation can result in MRD negativity and high rates of long term PFS. Clinical trial information: NCT03285321.

BackgroundUpsurge of adolescent obesity is an upcoming national public health concern. Obese adolescents are at significant risk of becoming obese adults and its co-morbidities. This study estimates the prevalence of adolescent obesity and explore the potential determinants among young adults residing in tribal populated villages of Chhattisgarh, India.MethodsA community-based nutritional survey was carried out among adolescent of the age group of 13-17 years.ResultsAmong 1,296 participants, 23.4 % of young adults were either overweight or obese. Higher family earnings (Odds ratio [OR], 2.79, 95% confidence interval [CI] 1.29-6.38), Skipping breakfast (3.09, 1.11-8.30), Television viewing > 2 hours/ day (2.16, 1.3-6.2), Energy intake (2.98, 1.19-15.6), significantly increased the risk of adolescent obesity.ConclusionPrevalence of adolescence obesity among the tribes is alarming and needs to be tackled with health system measures. Future research may require assessing the trajectory of obesity and related comorbidities in a tribal population.

Spiking neural networks, inspired by biological neural systems, could process immense volumes of spatio-temporal data by representing them as spikes. Here, we propose to implement compact, scalable, energy-efficient spiking neurons based on the unique insulator-metal transition in Vanadium dioxide $(VO_{2})$ which interact through memristive synapses, to emulate a Liquid State Machine (LSM). Further, we demonstrate the implementation of this recurrent neural network as a temporal auto-encoder, and adaptive channel equalizer for application in neuromorphic signal processing. Our approach provides a pathway to reduce component count $(50\ -100X)$ and improve energy efficiency $(> 50X)$ over conventional CMOS based implementations.

Not all computing problems are created equal. The inherent complexity of processing certain classes of problems using digital computers has inspired the exploration of alternate computing paradigms. Coupled oscillators exhibiting rich spatio-temporal dynamics have been proposed for solving hard optimization problems. However, the physical implementation of such systems has been constrained to small prototypes. Consequently, the computational properties of this paradigm remain inadequately explored. Here, we demonstrate an integrated circuit of thirty oscillators with highly reconfigurable coupling to compute optimal/near-optimal solutions to the archetypally hard Maximum Independent Set problem with over 90% accuracy. This platform uniquely enables us to characterize the dynamical and computational properties of this hardware approach. We show that the Maximum Independent Set is more challenging to compute in sparser graphs than in denser ones. Finally, using simulations we evaluate the scalability of the proposed approach. Our work marks an important step towards enabling application-specific analog computing platforms to solve computationally hard problems., Designing efficient analog dynamical systems for solving hard optimization problems remains a challenge. Here, the authors demonstrate a dynamical system of thirty oscillators with reconfigurable coupling to compute optimal/near-optimal solutions to the hard Maximum Independent Set problem with over 90% accuracy.

The diverse and fascinating properties of transition metal oxides stem from the strongly correlated electronic degrees of freedom; the scientific challenge and range of possible applications of these materials have caused fascination among physicists and materials scientists, thus capturing research efforts for nearly a century. Here, we focus on the binary VxOy and the ternary perovskite AVO3 and review the key aspects from the underlying physical framework and their basic properties, recent strides made in thin-film synthesis, to recent efforts to implement vanadium-based oxides for practical applications that augment existing technologies, which surpass limitations of conventional materials.

Hybrid-phase-transition FETs (Hyper-FETs) are recently proposed steep switching devices that utilize the phase transition materials (PTM) to achieve a boost in the ratio of ON ( ${I}_{{{\mathrm {ON}}}})$ and OFF currents ( ${I}_{{{\mathrm {OFF}}}})$ . Prototypical demonstrations of the Hyper-FET have shown performance improvement in comparison with conventional transistors, which motivates the evaluation of its device-circuit design space. In part I, we analyze the device aspects establishing the effects of the resistivity and phase transition thresholds of the PTM on the characteristics of Hyper-FETs. Our analysis shows that the ratio of insulating and metallic state resistivity ( $\rho _{\mathrm {INS}}$ and $\rho _{\mathrm {MET},}$ respectively) of the PTM needs to be higher than the ${I}_{{{\mathrm {ON}}}} /I_{{{\mathrm {OFF}}}}$ of its host transistor to achieve performance improvement in Hyper-FET. For a host transistor with $I_{{{\mathrm {OFF}}}} = 0.051\mu \text{A}/\mu \text{m}$ and ${I}_{{{\mathrm {ON}}}} = 191.5\mu \text{A}/\mu \text{m}$ , $\rho _{\mathrm {MET}} .cm and $\sim 7.5~\Omega $ .cm $ .cm is required to achieve proper device functionality with a boost in ${I}_{{{\mathrm {ON}}}}/{I}_{{{\mathrm {OFF}}}}$ . Additionally, we establish the ranges of phase transition thresholds that yield proper functionality of the Hyper-FETs considering different ${I}_{{{\mathrm {OFF}}}}$ targets. The methodology of choosing appropriate PTM geometry to achieve the target device characteristics is also described. We show that with proper design, Hyper-FETs achieve 94% larger ${I}_{{{\mathrm {ON}}}}$ at iso- ${I}_{{{\mathrm {OFF}}}}$ compared with a FinFET. We examine the circuit design aspects of Hyper-FET in part II.

9073 Background: Chemoimmunotherapy with a platinum doublet plus a checkpoint inhibitor (CPI) is a standard of care for pts with advanced NSCLC. While some pts experience prolonged responses to initial CPI therapy, the majority of pts will eventually experience PD. It is unknown if continuing CPI treatment beyond progression has any advantages in this setting. We report the results of a phase 2 trial of chemotherapy plus pembrolizumab in pts with advanced NSCLC previously treated with a PD-1 or PD-L1 inhibitor. Methods: Pts experiencing PD after clinical benefit to CPI (PFS > 3 months) were enrolled. Pts received pembrolizumab 200 mg q3wks plus next-line chemotherapy (gemcitabine 1000 mg/m2 IV D1 and D8 q3wks, or docetaxel 60-75 mg/m2 IV D1 q3wks, or pemetrexed 500 mg/m2 IV D1 q3wks [non-squamous histology only]). The primary endpoint was PFS by RECIST 1.1. Key secondary endpoints included ORR, OS, and toxicity. The null hypothesis was median 3-month PFS with pembrolizumab plus next-line chemotherapy and the alternative hypothesis was median 6-month PFS with pembrolizumab plus chemotherapy. Results: 35 pts were enrolled. Median follow-up was 18.1 months and median age 63 (44-80). 51.4% male and 48.6% female. 82.9% were current or former smokers. Histology included 74.3% with adenocarcinoma, 20% with squamous cell carcinoma, 5.7% with NSCLC NOS. Treatment regimens included pembrolizumab/docetaxel (40%), pembrolizumab/gemcitabine (45.7%), or pembrolizumab/pemetrexed (14.3%). Median number of cycles of pembrolizumab was 6 (1-31). Median PFS using RECIST 1.1 and irRECIST was 5.2 months (95% CI 3.6-11.2, p < 0.05) and 6.9 months (95% CI 3.8-12), respectively. Median OS was 26.8 months (95% CI 13.4-30.9). Best response using RECIST 1.1 was PR (23.5%) and SD (53%). 45.7% of pts experienced G3 or higher treatment-related AEs (TRAEs). Most common TRAEs were fatigue (60%), anemia (51.4%), and nausea (42.9%). There were no treatment related deaths. Conclusions: Pembrolizumab plus next-line chemotherapy in pts with advanced NSCLC who experienced PD after clinical benefit to CPI was associated with prolonged PFS compared with historical controls of single agent chemotherapy. Further investigations into which pts would benefit from continued CPI treatment after progression is warranted. Clinical trial information: NCT03083808.

According to the World Health Organization, "285 million people are estimated to be visually impaired worldwide" [1]. Several technologies such as automatic text readers, Braille note makers, and navigation assistance canes have been developed to assist the visually impaired. Concurrent advances in computer vision and hardware technologies provide opportunities for a visual-assistance system that can be used in multiple contexts. As part of the Visual Cortex on Silicon program, we have been developing interfaces, algorithms, and hardware platforms to assist the visually impaired with a focus on grocery shopping. This article describes the various features that we have incorporated into this visual-assistance system so that it can be used in multiple contexts.

We propose a novel static random access memory (SRAM) cell employing correlated material (CM) films in conjunction with the transistors to achieve higher read stability, write ability, and energy efficiency. The design of the proposed SRAM cell utilizes orders of magnitude difference in the resistance of the insulating and metallic phases of the CM to mitigate the design conflicts. By appropriately controlling the phase transitions in the CM films during SRAM operation through device–circuit codesign, we achieve 30% higher read static noise margin and 36% increase in the write margin over standard SRAM. The proposed design also leads to a 50% reduction in the leakage current due to high insulating state of the CM. This is achieved at 28% read time penalty. We also discuss the layout implications of our technique and present techniques to sustain no area overhead.

DC and pulse voltage-induced metal-insulator transition (MIT) in epitaxial VO2 two terminal devices were measured at various stage temperatures. The power needed to switch the device to the ON-state decrease linearly with increasing stage temperature, which can be explained by the Joule heating effect. During transient voltage induced MIT measurement, the incubation time varied across 6 orders of magnitude. Both DC I-V characteristic and incubation times calculated from the electrothermal simulations show good agreement with measured values, indicating Joule heating effect is the cause of MIT with no evidence of electronic effects. The width of the metallic filament in the ON-state of the device was extracted and simulated within the thermal model.

9032 Background: Consolidation checkpoint inhibitor therapy (CPI) for up to 1 year following chemoradiation (CRT) is a current standard of care for pts with inoperable stage III NSCLC. However, some pts are not able to complete 1 year of CPI due to immune-related adverse events (irAES). In multiple retrospective studies, pts with stage IV NSCLC treated with CPI who experience irAEs generally receive fewer cycles of CPI without a significant detrimental effect on efficacy. The association between irAEs and outcomes with consolidation CPI after CRT has never been reported. Here we report the association between irAEs and efficacy outcomes from the HCRN LUN 14-179, a single-arm phase II trial of consolidation pembrolizumab following concurrent CRT in pts with unresectable stage III NSCLC. Methods: After completion of CRT eligible pts with stage III NSCLC without PD received pembrolizumab 200 mg IV q 3 wks for up to 1 yr. Demographics, disease characteristics, and number of cycles of pembrolizumab received were reported in pts who had any grade irAEs (except pneumonitis which included grade >2 only) [Group A] and those without irAEs (except grade 1 pneumonitis) [Group B]. Chi-square test (or Fisher's Exact test) were used for comparisons for categorical variables and Wilcoxon test for continuous variables. The Kaplan-Meier method was used to analyze time to metastatic disease (TMDD), PFS, and OS. A log-rank test was used to compare groups. Results: 92 eligible pts for efficacy analysis were enrolled from March 2015 to November 2016. 4 yr OS estimate for all pts is 46.2%. Any grade irAEs (except grade I pneumonitis) (n = 37 pts) included pneumonitis (18.5%), colitis (3.3%), increased creatinine (5.4%), elevated transaminases (3.3%), hyperthyroidism (7.6%), hypothyroidism (13.0%). Grade ≥ 2 irAEs (n = 32 pts) included pneumonitis (18.5%), hypothyroidism (10.8%), and colitis (3.3%). Group A/B: male (21/38), female (16/17), current or former smoker (35/52), stage IIIA (20/35), stage IIIB (17/20), non-squamous (21/30), squamous (16/25). Median number of pembrolizumab cycles received in Group A/B pts were 9 vs 15 (p = 0.0942) respectively. 4 yr efficacy endpoints in Groups A/B were TMDD 35.3% vs 41.3% (p = 0.83), PFS 27.8% vs 28.7% (p = 0.97), OS 43.5% vs 47.9% (p = 0.99), respectively. Conclusions: Despite receiving fewer cycles of consolidation pembrolizumab, pts who experienced any grade irAEs (excluding grade 1 pneumonitis) did not have significantly reduced efficacy outcomes. Clinical trial information: NCT02343952.

While continuing the CMOS scaling-down becomes unprecedentedly more challenging than before, intensive exploration on beyond-CMOS nanodevice technologies is an appealing approach to further continue the power scaling-down. This chapter reviews some promising beyond-CMOS emerging transistor technologies, including Tunnel FETs, Ferroelectric FETs, and Hyper-FETs. Circuit design techniques based on these emerging devices are also reviewed to provide insights for future energy-efficient analog and digital signal processing. In addition to the opportunities, this chapter also discusses the challenges of emerging devices in circuit and systems.

We demonstrate a novel $\mathrm{VO}_{2}-\mathrm{based}$ edge-triggered (ET) three-terminal Mott switch that leverages the displacement current induced by the switching of the gate voltage pulse to trigger an IMT in the $\mathrm{VO}_{2}$ channel. The design overcomes a long-standing challenge of realizing a three-terminal $\mathrm{VO}_{2}$ switch due to the absence of field-effect induced IMT in VO 2 . The ET Mott switch also enables isolation between the input & the output (at steady state), and facilitates reduction in the effective trigger voltage in comparison to the two-terminal configuration. We show using simulations that these properties can be exploited to enable a BEOL-compatible 3T selector for MTJ-based cross-point memory, showing $3.4\times$ higher cell TMR, as well as 45% & 40% lower sneak-path current & power, respectively.

In this work, we demonstrate a novel Hybrid-FeFET (H-FeFET) that leverages the threshold switching characteristics of Ag/HfO 2 to overcome the fundamental trade-off between memory window MW /read current ratio (I read,1 /I read,0 ) , and program voltage (V prog )/maximum electric-field in standard FeFETs for non-volatile memory application. The H-FeFET incorporates the threshold switch (TS) in the source of the FeFET, and is designed to exhibit a ferroelectric state-dependent volatile HRS to LRS transition (I ON /I OFF >107) – during read, the TS turns ON only if the FeFET is in the low-V T SET state, and remains OFF if the FeFET is in the high-V T RESET state, thus, selectively suppressing the RESET read current. Leveraging this principle, the H-FeFET: a Demonstrates 77% higher MW and 1000× larger I read,1 /I read,0 compared to the FeFET, at iso-V prog (DC); (b) Enables 25% reduction in V prog at iso-I read,1 /I read,0 during pulse operation-facilitated by the 8× improvement in I read,1 /I read,0 ; (c) Exhibits 2.5×reduction in programming power at iso-I read,1 /I read,0 in the H-FeFET-based AND array architecture, as shown by simulations. Thus, the H-FeFET overcomes the FeFET design challenges while retaining its existing advantages, making it a promising candidate for nonvolatile memory applications.

Threshold switches (TS) exhibiting electrically driven phase transition between high resistance (insulating) and low resistance (metallic) states have shown an immense promise for several circuit applications [1]. $\mathrm{Ag}/\mathrm{HfO}_{2}/\mathrm{Pt}\ \mathrm{based}$ TS, a recent inclusion in this group, was reported to have high selectivity $(\sim 10^{7})$ and unipolar conduction [2], [3]. The unipolar nature of such a TS may be capitalized to achieve diode-like rectifying behavior with unique advantages. In this work, we discuss the merits $ofAg/HfO_{2}/Pt\ TS$ over standard diodes and present a Cockcroft-Walton multiplier (CWM) [4], [5] based on $Ag/HfO_{2}/Pt$ . The proposed CWM generates higher DC voltage from an AC input compared to standard CWM, utilizing (a) high selectivity (b) hysteretic behavior (c) abrupt $insulator\leftrightarrow metal$ transitions and (d) unipolar conduction $ofAg/HfO_{2}/Pt$ .

While Boolean logic has been the backbone of digital information processing, there exist classes of computationally hard problems wherein this paradigm is fundamentally inefficient. Vertex coloring of graphs, belonging to the class of combinatorial optimization, represents one such problem. It is well studied for its applications in data sciences, life sciences, social sciences and technology, and hence, motivates alternate, more efficient non-Boolean pathways towards its solution. Here we demonstrate a coupled relaxation oscillator based dynamical system that exploits insulator-metal transition in Vanadium Dioxide (VO

High power consumption has significantly increased the cooling cost in high-performance computation stations and limited the operation time in portable systems powered by batteries. Traditional power reduction mechanisms have limited traction in the post-Dennard Scaling landscape. Emerging research on new computation devices and associated architectures has shown three trends with the potential to greatly mitigate current power limitations. The first is to employ steep-slope transistors to enable fundamentally more efficient operation at reduced supply voltage in conventional Boolean logic, reducing dynamic power. The second is to employ brain-inspired computation paradigms, directly embodying computation mechanisms inspired by the brains, which have shown potential in extremely efficient, if approximate, processing with silicon-neuron networks. The third is “let physics do the computation”, which focuses on using the intrinsic operation mechanism of devices (such as coupled oscillators) to do the approximate computation, instead of building complex circuits to carry out the same function. This paper first describes these three trends, and then proposes the use of the hybrid-phase-transition-FET (Hyper-FET), a device that could be configured as a steep-slope transistor, a spiking neuron cell, or an oscillator, as the device of choice for carrying these three trends forward. We discuss how a single class of device can be configured for these multiple use cases, and provide in-depth examination and analysis for a case study of building coupled-oscillator systems using Hyper-FETs for image processing. Performance benchmarking highlights the potential of significantly higher energy efficiency than dedicated CMOS accelerators at the same technology node.

We establish an active electrode (AE) selection criterion for volatile and non-volatile switching in metallic conducting bridge (CB) RAM, relevant to cross-point selector and memory applications. Using first principle calculations, we show that: (a) volatile versus non-volatile switching is determined by the energy difference A between the cluster configuration of the AE atoms in the high-resistance (HRS) state, and the filament configuration of the AE atoms in the low-resistance (LRS) state; volatile switching is achieved when A is large, whereas the system will exhibit non-volatile behavior when A ∼ 0; (b) the maximum LRS (ON-state) current, Imax that can be delivered while sustaining volatile (selector) operation is proportional to the magnitude of A for the AE. Using molecular dynamical (MD) + NEGF transport simulations, supported by experiments, we confirm the volatile (selector) switching characteristics of Ag/HfO2/Pt, and the non-volatile (memory) switching characteristics of Co/HfO2/Pt, as predicted by our criterion; the corresponding temporal characteristics are also evaluated. Finally, we calculate the expected switching characteristics for various active electrodes (AEs), showing excellent agreement with experimental results. Our findings enable the design of CBRAM-based selectors and memory with the required switching properties.

We report the results of finite element simulations of the ON state characteristic of VO

Phase transition materials (PTM) [1] have shown an immense promise for several applications such as realizing steep switching Phase-FETs [1], augmenting the read operation of memories [2-3], non-linear selectors for cross-point memory arrays [4] and in the design of neurons [5] and oscillators [6]. Their unique properties open up new avenues for other designs as well and therefore, there is a need to identify such opportunities to harness the full potential of PTM. In this work, we propose a low area low power current sense amplifier (SA) utilizing distinct properties of PTM such as abrupt insulator ↔ metal transitions and high resistivity ratio.

In this paper we review recent work on computational paradigms involving coupled relaxation oscillators built using metal-insulator-transition (MIT) devices. Such oscillators made using MIT devices based on Vanadium-Dioxide thin films are very compact and can be realized in hardware. Networks of such oscillators have interesting phase and frequency dynamics which can be programmed to solve computationally hard problems.

Two-dimensional materials are being investigated for potential nanoelectronic applications such as transistors for scaled technology nodes. Here we investigate the possibility of further augmenting the performance of such 2D materials through a novel device concept known as the hybrid-phase transition FET or Phase-FET. The MoS 2 based Phase-FET incorporates an insulator-to-metal transition material VO 2 integrated in series with the source of a MOSFET, which provides an internal amplification across the insulator-to-metal transition and results in steep slope switching.

As complementary metal-oxide-semiconductor (CMOS) scaling continues to offer insurmountable challenges, questions about the performance capabilities of Boolean, digital machine based on Von-Neumann architecture, when operated within a power budget, have also surfaced. Research has started in earnest to identify alternative computing paradigms that provide orders of magnitude improvement in power-performance for specific tasks such as graph traversal, image recognition, template matching, and so on. Further, post-CMOS device technologies have emerged that realize computing elements which are neither CMOS replacements nor suited to work as a binary switch. In this paper, we present the realization of coupled and scalable relaxation-oscillators utilizing the metal-insulator-metal transition of vanadium-dioxide (VO2) thin films. We demonstrate the potential use of such a system in a non-Boolean computing paradigm and demonstrate pattern recognition, as one possible application using such a system.

We locally investigate the electronic transport through individual tunnel junctions containing a 10 nm thin film of vanadium dioxide (VO2) across its thermally induced phase transition. The insulator-to-metal phase transition in the VO2 film collapses the Hubbard gap (experimentally determined to be 0.4 ± 0.07 V), leading to several orders of magnitude change in tunnel conductance. We quantitatively evaluate underlying transport mechanisms via theoretical quantum mechanical transport calculations which show excellent agreement with the experimental results.

We demonstrate a novel Ag/HfO 2 based threshold switch (TS) with a selectivity∼107, a high ON-state current (Ion) of 100 μA, and ∼10pA leakage current. The thresholding characteristics of the TS result from electrically triggered spontaneous formation and rupture of an Ag filament which acts an interstitial dopant in the HfO2 insulating matrix. Further, we harness the extreme non-linearity of the TS in (1) Selectors for Phase Change Memory (PCM) based cross-point memory. We show through array level simulations of a 1024kb memory, a read margin of 28% and write margin of 32% for a leakage power of ds ), and >10x Ion improvement over the conventional FET (at iso-I off ) at T=90C (50x at T=25C); making this a promising TS for both emerging memory, and steep-slope transistor applications.

Cellular signaling is in part regulated by the composition and subcellular localization of a series of protein interactions that collectively form a signaling complex. Using the α7 nicotinic acetylcholine receptor (α7nAChR) as a proof-of-concept target, we developed a platform to identify functional modulators (or auxiliary proteins) of α7nAChR signaling. The Broad cDNA library was transiently cotransfected with α7nAChR cDNA in HEK293T cells in a high-throughput fashion. Using this approach in combination with a functional assay, we identified positive modulators of α7nAChR activity. We identified known positive modulators/auxiliary proteins present in the cDNA library that regulate α7nAChR signaling, in addition to identifying novel modulators of α7nAChR signaling. These included NACHO, SPDYE11, TCF4, and ZC3H12A, all of which increased PNU-120596-mediated nicotine-dependent calcium flux. Importantly, these auxiliary proteins did not modulate GluR1(o)-mediated Ca flux. To elucidate a possible mechanism of action, we employed an α7nAChR-HA surface staining assay. NACHO enhanced α7nAChR surface expression; however, the mechanism responsible for the SPDYE11-, TCF4-, and ZC3H12A-dependent modulation of α7nAChR has yet to be defined. This report describes the development and validation of a high-throughput, genome-wide cDNA screening platform coupled to FLIPR functional assays in order to identify functional modulators of α7nAChR signaling.

This chapter focuses on recent works in experimentally demonstrating tunable coupled relaxation oscillators, based on the phenomenon of insulator‐metal transition in vanadium dioxide (VO 2 ), as an efficient non‐Boolean computational primitive capable of performing the visual saliency task. The chapter exploits the phase synchronization dynamics of pairs of coupled oscillators to compute a fractional distance norm that is suitable for associative computing. Complementary metal‐oxide‐semiconductor (CMOS) transistors supporting the Boolean computational framework have been the backbone of modern computation, and have fueled the information technology revolution for the past four decades. Mathematically, the quantification of the degree of match between two quantities requires the calculation of a distance between two points that represents the two quantities in a high‐dimensional space. It turns out that the so‐called ‘Boolean bottleneck’ arises from the requirement of a significant number of power‐intensive multiply‐accumulate (MAC) operations involved in the calculation of the distance norm.

Conventional CMOS scaling and the Moore's law have been the cornerstone of progress in computing hardware technology. However, with dimensional scaling expected to end soon, there is a pressing need to find the next transistor solution that can continue to support the technology revolution. Will this hardware solution be an enhanced or an augmented version of MOSFET or a switch based on a radically new switching mechanism. Ultimately, do we require a complete deviation from the Boolean paradigm itself? In this invited paper, we will review some of the actively pursued state-of-the-art transistor and related concepts. While it remains unclear which of these options will eventually make it into commercial products, we will argue-based on lessons learnt from the past two decades of transistor development-that sustained and systematic research with careful benchmarking remains the key to success in the quest for the new switch.

In this paper we review recent work on novel computing paradigms using coupled oscillatory dynamical systems. We explore systems of relaxation oscillators based on linear state transitioning devices, which switch between two discrete states with hysteresis. By harnessing the dynamics of complex, connected systems we embrace the philosophy of "let physics do the computing" and demonstrate how complex phase and frequency dynamics of such systems can be controlled, programmed and observed to solve computationally hard problems. Although our discussion in this paper is limited to Insulator-to-Metallic (IMT) state transition devices, the general philosophy of such computing paradigms can be translated to other mediums including optical systems. We present the necessary mathematical treatments necessary to understand the time evolution of these systems and demonstrate through recent experimental results the potential of such computational primitives., Submitted to Journal of Nanophotonics for review

Coupled oscillators provide an efficient non-Boolean paradigm for solving a variety of computationally intensive problems in computer vision. This motivates the realization of large networks of low-power coupled oscillators. In this work, we experimentally demonstrate: (i) a relaxation oscillator based on the insulator-metal transition (IMT) in vanadium dioxide (VO 2 ) with record low DC input (peak) power of ∼23 µW; (ii) a network of coupled VO 2 oscillators with record number of elements (6 oscillators) which perform image processing functionalities in high dimensional space like color detection and morphological operations such as dilation and erosion). Calibrated simulations show that 10× reduction in power compared to a 32 nm CMOS accelerator at iso-throughput.

Insulator-metal transitions (IMTs) are the subject of intense fundamental and applied research including their potential applications in electronic devices like coupled relaxation oscillators [1], neuromorphic devices [2], Phase FETs [3], and RF switches [4]. A key requirement for practical device application of IMT materials is that the IMT temperature (IWr) should be greater than 358 K (85C) which is the operating temperature of electronic chips (Fig. 1). In this work, we investigate the electrically induced IMT in epitaxially grown 0.3% tensile strained Ca 2 RuO 4 thin films wherein strain engineering increases the transition temperature (Timt) to more than 550K from a bulk value of ∼357K (ΔΤ I μT >190K). Using systematic DC and transient I-V measurements, we show that the origin of the electrically induced IMT in Ca 2 RuO 4 is current induced self-heating.

Vanadium dioxide (VO 2 ), which exhibits electrically induced abrupt insulator-to-metal phase transition (IMT), is monolithically integrated with Silicon MOSFET to demonstrate a steep-slope (sub-kT/q) Phase-Transition FET (Phase-FET). The Phase-FET exhibits switching-slope (SS) of 8mV/decade leading to 36% increase in ON current (I ON ) over baseline MOSFET. We analyze the electrical characteristics of several threshold-switching materials with enhanced resistivity ratios (>105) beyond VO 2 and harness them to enhance the performance of 14nm node FinFETs. Our analysis shows that up to 2.9× increase in I ON , and 1.86× reduction in energy at (iso-delay) for an 11 stage ring oscillator (RO) is achievable with Phase FETs using Cu-doped HfO 2 threshold switches.

While Boolean logic has been the backbone of information processing, there are computationally hard problems like optimization and classification wherein this conventional paradigm is less efficient. This motivates us to explore new pathways to their solution. In this invited talk, we describe an experimental testbed using coupled relaxation oscillator arrays that exploit the insulator-metal phase transitions in the correlated material, vanadium dioxide (VO 2 ), to realize a chip scale coupled dynamical system. Our work is inspired by the understanding that associative computing finds a natural analogue in the energy minimization processes embedded within the spatiotemporal dynamics of coupled systems. Our work not only elucidates a physics-based computing method but also presents opportunities for customized co-processors for solving computationally hard problems efficiently.

The switching dynamics of electrically driven insulator-to-metal transition (IMT) and metal-to-insulator transition (MIT) in vanadium dioxide are investigated. The transient response of time domain measurements are modeled using a domain based 2-D heterogeneous resistive network, taking into account local electronic potential and local Joule heating. It reveals, the switching time is dominated by a spatially non-uniform percolation of the metallic phase during the IMT driven by electro-thermal forces. We demonstrate an IMT switching time of 793ps in scaled VO 2 devices and project IMT and MIT switching speed for scaled devices.

Cross-point architectures are promising for designing dense memory arrays. However, sneak current paths in a cross-point array necessitates the use of non-linear selectors. In this paper, we analyze the potential of employing correlated materials exhibiting abrupt insulator-metal transitions as selectors to design cross-point memories based on magnetic tunnel junctions (MTJs). We analyze the properties of the correlated materials and co-design MTJs and the selector to optimize the energy efficiency and robustness of the memory array. Our analysis points to the need of a correlated material with a large ratio of insulator and metal resistivities along with appropriate critical currents for the phase transitions (the values of which depend on the absolute value of the resistivities). We discuss that the design constraints lead to a restriction on the range of the selector length, which is closely related to the oxide thickness of the MTJ. Comparison of the cross-point architecture with standard architecture shows the benefits in the former in terms of 7% larger sense margin and 5X higher integration density at iso-read stability. However, this comes at the cost of 2X lower write speed (due to two-cycle write) and 11%–19% increase in the read/write power (due to sneak current in the cross-point array).

We analyze the effect of hysteresis in the correlated material (CM) based selector devices on the choice of the word-line and bit-line voltages of a cross-point memory array. Considering a magnetic tunnel junction as the memory device, we also evaluate the dependence of array leakage and performance on the CM characteristics. While insulator-to-metal transition (IMT) in the CM plays a pivotal role in determining the voltage biases for proper functionality, we show that metal-to-insulator transition (MIT) also has an important effect on the array power-performance. If MIT switching time is large compared to the setup time, the read/write speed may be limited by MIT, resulting in performance loss. We show that the performance can be recovered by choosing appropriate voltage biases. We define the region of operation for the voltage biases constrained by MIT to ensure no performance penalty due to metal-to-insulator transition. For the read operation, MIT constrained region of operation leads to minimal or no leakage penalty. Thus, optimal choice of bias voltages for read yields maximum performance and energy efficiency. However, for the write operation, high write voltage shrinks the region of operation, thus offering limited choices for the voltages, leading to leakage increase. The leakage penalty reduces with decreasing hysteresis of the CM. While leakage increase at iso-performance can be as large as 21X for 75mV of hysteresis, it reduces to 2.6X for hysteresis of 28mV. For hysteresis > 100 mV, the MIT constrained region of operation vanishes and the only design choice that remains is increasing the write cycle time.

Collective interactions in functional materials can enable novel macroscopic properties like insulator-to-metal transitions. While implementing such materials into field-effect-transistor technology can potentially augment current state-of-the-art devices by providing unique routes to overcome their conventional limits, attempts to harness the insulator-to-metal transition for high-performance transistors have experienced little success. Here, we demonstrate a pathway for harnessing the abrupt resistivity transformation across the insulator-to-metal transition in vanadium dioxide (VO2), to design a hybrid-phase-transition field-effect transistor that exhibits gate controlled steep (‘sub-kT/q') and reversible switching at room temperature. The transistor design, wherein VO2 is implemented in series with the field-effect transistor's source rather than into the channel, exploits negative differential resistance induced across the VO2 to create an internal amplifier that facilitates enhanced performance over a conventional field-effect transistor. Our approach enables low-voltage complementary n-type and p-type transistor operation as demonstrated here, and is applicable to other insulator-to-metal transition materials, offering tantalizing possibilities for energy-efficient logic and memory applications., The intrinsic properties of conventional semiconductors limits the speed and efficiency of field-effect transistors. Here, the authors take advantage of the insulator-to-metal transition in vanadium dioxide to create a transistor with reversible and steep-slope switching at room temperature.

We propose a technique based on connecting CM like VO 2 in parallel with the MTJ in the read path of multi-port MRAMs. Utilizing insulator-metal transitions in CM, the proposed cell achieves 1.7X to 4.3X improvement in cell TMR (CTMR) along with 7% to 22% higher read disturb margin compared to a baseline cell. Due to the separation of read-write paths in multi-port MRAMs, the CM has no effect on the write operation. The proposed idea is not limited to VO 2 and its benefits may be further enhanced by exploring other suitable CMs [6] or by tuning the properties like resistivities, critical currents and thermal stability by techniques like strain [7] or Cr doping [8].

This paper deals with modeling and simulation of a new family of two-terminal devices fabricated with vanadium dioxide material. Such devices allow realization of very compact relaxation nano-oscillators that can be connected electronically to form arrays of coupled oscillators. Challenging applications of oscillator arrays include the realization of multiphase signal generators and massively parallel brain-inspired neurocomputing. In the paper, a circuit-level model of the vanadium dioxide device is provided which enables extensive electrical simulations of oscillator systems built on the device. The proposed model is exploited to explain the dynamics of vanadium dioxide relaxation oscillators as well as to accomplish a robust parameter design. Applications to the realization of voltage-controlled oscillators and of multiphase oscillator arrays are illustrated.

An original circuit-level model of two-terminal vanadium dioxide electron devices exhibiting electronic hysteresis is presented. Such devices allow realisation of very compact relaxation nano-oscillators that potentially can be used in bio-inspired neurocomputing. The proposed model is exploited to determine the parameters, values that ensure stable periodic oscillations.

The intrinsic field effect, the change in surface conductance with an applied transverse electric field, of prototypal strongly correlated VO2 has remained elusive. Here we report its measurement enabled by epitaxial VO2 and atomic layer deposited high-kappa dielectrics. Oxygen migration, joule heating, and the linked field-induced phase transition are precluded. The field effect can be understood in terms of field-induced carriers with densities up to similar to 5 x 10(13) cm(-2) which are strongly localized, as shown by their low, thermally activated mobility (similar to 1 x 10(-3) cm(2)/Vs at 300 K). These carriers show behavior consistent with that of Holstein polarons and strongly impact the (opto) electronics of VO2.

Glioblastoma multiforme (GBM) remains a common and deadly primary brain tumor. Current treatment includes surgical resection with adjuvant chemotherapy and radiotherapy. However, median survival remains less than 15 months mainly due to tumor recurrence and drug resistance. SapC-DOPS, also called BXQ-350, is a stable protein-lipid nanovesicle that has been shown to have anti-GBM activity and is now in a Phase 1 clinical trial. SapC-DOPS selectively targets phosphatidylserine (PS) which is abnormally exposed on the cancer cell surface. It is known that the antitumor efficacy of SapC-DOPS is correlated with the level of surface PS on GBM cells. AS1411, a stable G-rich DNA oligo and the first aptamer to progress to clinical trials, has anticancer activity via a methuosis-induction pathway. The aptamer predominantly functions via nucleolin binding in tumor cells. However, methuosis-induced cell death by AS1411 in GBM cells has not previously been described. Our morphologic analyses of U87-MG cells treated with AS1411 showed vacuolization similar to the known methuosis inducer, MIPP. Utilizing flow-cytometry we demonstrated that treatment of U87-MG cells with AS1411 induced a time-dependent increase in surface PS, with greater than 2-fold increase in surface PS at the 72-hour time point (p < 0.005). Interestingly, AS1411 mediated increase in surface PS resulted in enhanced response to SapC-DOPS. Combination treatment with various concentrations of SapC-DOPS and AS1411 showed increased antitumor effects against U87-MG cells (p < 0.01). Our study elucidates a potential role of AS1411 in sensitizing GBM to SapC-DOPS through surface PS elevation. This combination therapy may provide a new clinical modality for treating GBM patients.