Rapid, quantitative therapeutic screening for Alzheimer's enzymes enabled by optimal signal transduction with transistors.

We show that commercially sourced n-channel silicon field-effect transistors (nFETs) operating above their threshold voltage with closed loop feedback to maintain a constant channel current allow a pH readout resolution of (7.2 ± 0.3) × 10-3 at a bandwidth of 10 Hz, or ≈3-fold better than the open loop operation commonly employed by integrated ion-sensitive field-effect transistors (ISFETs). We leveraged the improved nFET performance to measure the change in solution pH arising from the activity of a pathological form of the kinase Cdk5, an enzyme implicated in Alzheimer's disease, and showed quantitative agreement with previous measurements. The improved pH resolution was realized while the devices were operated in a remote sensing configuration with the pH sensing element off-chip and connected electrically to the FET gate terminal. We compared these results with those measured by using a custom-built dual-gate 2D field-effect transistor (dg2DFET) fabricated with 2D semi-conducting MoS2 channels and a signal amplification of 8. Under identical solution conditions the nFET performance approached the dg2DFETs pH resolution of (3.9 ± 0.7) × 10-3. Finally, using the nFETs, we demonstrated the effectiveness of a custom polypeptide, p5, as a therapeutic agent in restoring the function of Cdk5. We expect that the straight-forward modifications to commercially sourced nFETs demonstrated here will lower the barrier to widespread adoption of these remote-gate devices and enable sensitive bioanalytical measurements for high throughput screening in drug discovery and precision medicine applications.

Nondispersive Infrared Gas Analyzer for Partial Pressure Measurements of a Tantalum Alkylamide During Vapor Deposition Processes.

A nondispersive infrared gas analyzer was demonstrated for investigating metal alkylamide precursor delivery for microelectronics vapor deposition processes. The nondispersive infrared analyzer was designed to simultaneously measure the partial pressure of pentakis(dimethylamido) tantalum, a metal precursor employed in high volume manufacturing vapor deposition processes to deposit tantalum nitride, and dimethylamine, the primary decomposition product of pentakis(dimethylamido) tantalum at typical delivery conditions for these applications. This sensor was based on direct absorption of pentakis(dimethylamido) tantalum and dimethylamine in the fingerprint spectral region. The nondispersive infrared analyzer optical response was calibrated by measuring absorbance as a function of dimethylamine and pentakis(dimethylamido) tantalum density. The difference between the mass of material removed from the ampoule during flow tests as measured gravimetrically and as determined optically, by calculating flow rates from the nondispersive infrared analyzer measurements, was only ≈2 %. The minimum detectable molecular densities for pentakis(dimethylamido) tantalum and dimethylamine were ≈2 × 1013 cm-3 and ≈5 × 1014 cm-3, respectively (with no signal averaging and for a sampling rate of 200 Hz), and the corresponding partial pressures were ≈0.1 Pa and ≈2 Pa for pentakis(dimethylamido) tantalum and dimethylamine, respectively (for an optical flow cell temperature of 93 ℃). Pentakis(dimethylamido) tantalum could be detected at all conditions of this investigation and likely the majority of conditions relevant to high volume manufacturing tantalum nitride deposition. Dimethylamine was not detected at all conditions in this study, because of a lower nondispersive infrared analyzer sensitivity to dimethylamine compared to pentakis(dimethylamido) tantalum and because conditions of this study were selected to minimize DMA production. While this nondispersive infrared gas analyzer was specifically developed for pentakis(dimethylamido) tantalum and dimethylamine, it is suitable for characterizing the vapor delivery of other metal alkylamide precursors and the corresponding amine decomposition products, although in the case of some metal alkylamides a different bandpass filter would be required.

Reproducible Performance Improvements to Monolayer MoS2 Transistors through Exposed Material Forming Gas Annealing.

Metal-mediated exfoliation has been demonstrated as a promising approach for obtaining large-area flakes of two-dimensional (2D) materials to fabricate prototypical nanoelectronics. However, several processing challenges related to organic contamination at the interface of a 2D material and gate oxide must be overcome to realize robust devices with high yields. Here, we demonstrate an optimized process to realize high-performance field-effect transistor (FET) arrays from large-area (∼5000 µm2), monolayer MoS2 with a yield of 85%. A central element of this process is an exposed material forming gas anneal (EM-FGA) that results in uniform FET performance metrics (i.e., field-effect mobilities, threshold voltages, and contact performance). Complementary analytical measurements show that the EM-FGA process reduces deleterious channel doping effects by decreasing organic contamination while also reducing the prevalence of insulating molybdenum oxide, effectively improving the MoS2-gate oxide interface. The uniform FET performance metrics and high device yield achieved by applying the EM-FGA technique on large-area 2D material flakes will help advance the fabrication of complex 2D nanoelectronic devices and demonstrate the need for improved engineering of the 2D material-gate oxide interface.

Apparatus for Characterizing Gas-Phase Chemical Precursor Delivery for Thin Film Deposition Processes.

Thin film vapor deposition processes, e.g., chemical vapor deposition, are widely used in high-volume manufacturing of electronic and optoelectronic devices. Ensuring desired film properties and maximizing process yields require control of the chemical precursor flux to the deposition surface. However, achieving the desired control can be difficult due to numerous factors, including delivery system design, ampoule configuration, and precursor properties. This report describes an apparatus designed to investigate such factors. The apparatus simulates a single precursor delivery line, e.g., in a chemical vapor deposition tool, with flow control, pressure monitoring, and a precursor-containing ampoule. It also incorporates an optical flow cell downstream of the ampoule to permit optical measurements of precursor density in the gas stream. From such measurements, the precursor flow rate can be determined, and, for selected conditions, the precursor partial pressure in the headspace can be estimated. These capabilities permit this apparatus to be used for investigating a variety of factors that affect delivery processes. The methods of determining the pressure to (1) calculate the precursor flow rate and (2) estimate the headspace pressure are discussed, as are some of the errors associated with these methods. While this apparatus can be used under a variety of conditions and configurations relevant to deposition processes, the emphasis here is on low-volatility precursors that are delivered at total pressures less than about 13 kPa downstream of the ampoule. An important goal of this work is to provide data that could facilitate both deposition process optimization and ampoule design refinement.

Experiment-based modelling of a vapor draw ampoule used for low-volatility precursors.

Delivery of low-volatility precursors is a continuing challenge for chemical vapor deposition and atomic layer deposition processes used for microelectronics manufacturing. To aid in addressing this problem, we have recently developed an inline measurement capable of monitoring precursor delivery. Motivated by a desire to better understand the origins of what is now observable, this study uses computational fluid dynamics and a relatively simple model to simulate the delivery of pentakis(dimethylamido)tantalum (PDMAT) from a commercial vapor draw ampoule. Parameters used in the model are obtained by fitting the performance of the ampoule to a limited dataset of PDMAT delivery rates obtained experimentally using a non-dispersive infrared sensor. The model shows good agreement with a much larger experimental dataset over a range of conditions in both pulsed and continuously flowing operation. The combined approach of experiment and simulation provides a means to understand the phenomena occurring during precursor delivery both quantitatively and qualitatively.

Characterization of bubbler performance for low-volatility liquid precursor delivery.

The performance of a bubbler to deliver the low-volatility, liquid cobalt precurso µ 2 - η 2 -(tBu-acetylene) dicobalthexacarbonyl (CCTBA) for reduced-pressure chemical vapor deposition and atomic layer deposition processes was characterized. A relatively large process window was investigated by varying carrier gas flow rate, system pressure, and bubbler temperature. For this range of conditions, the CCTBA partial pressure was measured using a custom-designed non-dispersive infrared gas analyzer, and the CCTBA flow rates were derived from these partial pressure measurements. The dependence of CCTBA flow rate on these process parameters was modeled to obtain a deeper understanding of the factors influencing bubbler performance. Good agreement between measured and modeled CCTBA flow rates was obtained using a model in which a constant CCTBA partial pressure in the bubbler head space for a given bubbler temperature was assumed and in which the pressure drop between the bubbler head space and the pressure measurement location was included. The dependence of CCTBA head space partial pressure on temperature was parameterized in the form of the August equation, which is commonly used to describe the temperature-dependence of vapor pressure. While this report was focused specifically on CCTBA, the results are expected to apply to other low-volatility, liquid precursors of interest in vapor deposition processes.

Evaluation of Silicon Wafer-Based Internal Reflection Elements for Use with in Situ Fourier Transform Infrared (FT-IR) Spectroscopy.

Silicon wafer-based internal reflection elements (IREs) present many practical advantages over the prisms conventionally used for attenuated total reflection (ATR) spectroscopy in the infrared. We examine two methods of using minimally prepared IREs that have appeared in the literature, edge-coupled (EC) and prism-coupled (PC), in conjunction with a liquid flow cell. Polarization measurements show that radiation entering the PC-IRE becomes depolarized due to stress-induced birefringence, and transmission through the edge of the EC-IRE also affects the polarization state. Quantification of the noise and a calibration using a series of sodium acetate solutions show the sensitivity of the PC-IRE outweighs the lower noise obtainable with the EC-IRE.

In situ infrared spectroscopy during La2O3 ALD using La( i PrCp)3 and H2O.

Infrared spectra of surface species have been obtained during atomic layer deposition using tris(isopropylcyclopentadienyl)lanthanum, La(iPrCp)3, and water as precursors at 160 °C and 350 °C. Gas-phase spectra of La(iPrCp)3are obtained for comparison. At low temperature, ligand exchange is seen to occur, and carbonate formation is found. With extended purging, the organic ligands are found to be stable on the surface, and carbonates are not formed. These observations indicate that carbonate formation is occurring during exposure to the precursors. At high temperature, the La precursor is observed to decompose leaving an opaque deposit containing relatively little hydrogen.

Nondispersive Infrared Gas Analyzer for Vapor Density Measurements of a Carbonyl-Containing Organometallic Cobalt Precursor.

A nondispersive infrared (NDIR) gas analyzer was demonstrated for measuring the vapor-phase density of the carbonyl-containing organometallic cobalt precurso µ2-η2-(tBu-acetylene) dicobalthexacarbonyl (CCTBA). This sensor was based on direct absorption by CCTBA vapor in the C≡O stretching spectral region and utilized a stable, broadband IR filament source, an optical chopper to modulate the source, a bandpass filter for wavelength isolation, and an InSb detector. The optical system was calibrated by selecting a calibration factor to convert CCTBA absorbance to a partial pressure that, when used to calculate CCTBA flow rate and CCTBA mass removed from the ampoule, resulted in an optically determined mass that was nominally equal to a gravimetrically-determined mass. In situ Fourier transform infrared (FT-IR) spectroscopy was performed simultaneously with the NDIR gas analyzer measurements under selected conditions in order to characterize potential spectroscopic interferences. Interference due to CO evolution from CCTBA was found to be small under the flow conditions employed here. A CCTBA minimum detectable molecular density as low as ≈3 × 1013 cm-3 was calculated (with no signal averaging and for a sampling rate of 200 Hz). While this NDIR gas analyzer was specifically tested for CCTBA, it is suitable for characterizing the vapor delivery of a range of carbonyl-containing precursors.

In Situ Time-Resolved Attenuated Total Reflectance Infrared Spectroscopy for Probing Metal-Organic Framework Thin Film Growth.

In situ chemical measurements of solution/surface reactions during metal-organic framework (MOF) thin film growth can provide valuable information about the mechanistic and kinetic aspects of key reaction steps, and allow control over crystal quality and material properties. Here, we report a new approach to study the growth of MOF thin films in a flow cell using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). Real-time spectra recorded during continuous flow synthesis were used to investigate the mechanism and kinetics that govern the formation of (Zn, Cu) hydroxy double salts (HDSs) from ZnO thin films and the subsequent conversion of HDS to HKUST-1. We found that both reactions follow pseudo-first order kinetics. Real-time measurements also revealed that the limited mass transport of reactants may lead to partial conversion of ZnO to HDS and therefore leaves an interfacial ZnO layer beneath the HDS film providing strong adhesion of the HKUST-1 coating to the substrate. This in situ flow-cell ATR-FTIR method is generalizable for studying the dynamic processes of MOF thin film growth, and could be used for other solid/liquid reaction systems involving thin films.

Measurements of metal alkylamide density during atomic layer deposition using a mid-infrared light-emitting diode (LED) source.

A nondispersive infrared (NDIR) gas analyzer that utilizes a mid-infrared light emitting diode (LED) source was demonstrated for monitoring the metal alkylamide compound tetrakis(dimethylamido) titanium (TDMAT), Ti[N(CH3)2]4. This NDIR gas analyzer was based on direct absorption measurement of TDMAT vapor in the C-H stretching spectral region, a spectral region accessed using a LED with a nominal emission center wavelength of 3.65 µm. The sensitivity of this technique to TDMAT was determined by comparing the absorbance measured using this technique to the TDMAT density as determined using in situ Fourier transform IR (FT-IR) spectroscopy. Fourier transform IR spectroscopy was employed because this technique could be used to (1) quantify TDMAT density in the presence of a carrier gas (the presence of which precludes the use of a capacitance manometer to establish TDMAT density) and (2) distinguish between TDMAT and other gas-phase species containing IR-active C-H stretching modes (allowing separation of the signal from the LED-based optical system into fractions due to TDMAT and other species, when necessary). During TDMAT-only delivery, i.e., in the absence of co-reactants and deposition products, TDMAT minimum detectable molecular densities as low as ≈4 × 10(12) cm(-3) were demonstrated, with short measurement times and appropriate signal averaging. Reactions involving TDMAT often result in the evolution of the reaction product dimethylamine (DMA), both as a thermal decomposition product in a TDMAT ampoule and as a deposition reaction product in the deposition chamber. Hence, the presence of DMA represents a significant potential interference for this technique, and therefore, the sensitivity of this technique to DMA was also determined by measuring DMA absorbance as a function of pressure. The ratio of the TDMAT sensitivity to the DMA sensitivity was determined to be ≈6.0. To further examine the selectivity of this technique, measurements were also performed during atomic layer deposition (ALD) of titanium dioxide using TDMAT and water. During ALD, potential interferences were expected from the evolution of DMA due to deposition reactions and the deposition on the windows of species containing IR-active C-H stretching modes. It was found that the interfering effects of the evolution of DMA and deposition of species on the windows corresponded to a maximum of only ≈6% of the total observed TDMAT density. However, this level of interference likely is relatively low compared to a typical chemical vapor deposition process in which co-reactants are introduced into the chamber at the same time.

Time-resolved surface infrared spectroscopy during atomic layer deposition.

This work presents a novel method for obtaining surface infrared spectra with sub-second time resolution during atomic layer deposition (ALD). Using a rapid-scan Fourier transform infrared (FT-IR) spectrometer, we obtain a series of synchronized interferograms (120 ms) during multiple ALD cycles to observe the dynamics of an average ALD cycle. We use a buried metal layer (BML) substrate to enhance absorption by the surface species. The surface selection rules of the BML allow us to determine the contribution from the substrate surface as opposed to that from gas-phase molecules and species adsorbed at the windows. In addition, we use simulation to examine the origins of increased reflectivity associated with phonon absorption by the oxide layers. The simulations are also used to determine the decay in enhancement by the buried metal layer substrate as the oxide layer grows during the experiment. These calculations are used to estimate the optimal number of ALD cycles for our experimental method.

Quantum cascade laser-based measurement of metal alkylamide density during atomic layer deposition.

An in situ gas-phase diagnostic for the metal alkylamide compound tetrakis(ethylmethylamido) hafnium (TEMAH), Hf[N(C(2)H(5))(CH(3))](4), was demonstrated. This diagnostic is based on direct absorption measurement of TEMAH vapor using an external cavity quantum cascade laser emitting at 979 cm(-1), coinciding with the most intense TEMAH absorption in the mid-infrared spectral region, and employing 50 kHz amplitude modulation with synchronous detection. Measurements were performed in a single-pass configuration in a research-grade atomic layer deposition (ALD) chamber. To examine the detection limit of this technique for use as a TEMAH delivery monitor, this technique was demonstrated in the absence of any other deposition reactants or products, and to examine the selectivity of this technique in the presence of deposition products that potentially interfere with detection of TEMAH vapor, it was demonstrated during ALD of hafnium oxide using TEMAH and water. This technique successfully detected TEMAH at molecular densities present during simulated industrial ALD conditions. During hafnium oxide ALD using TEMAH and water, absorbance from gas-phase reaction products did not interfere with TEMAH measurements while absorption by reaction products deposited on the optical windows did interfere, although interfering absorption by deposited reaction products corresponded to only ≈4% of the total derived TEMAH density. With short measurement times and appropriate signal averaging, estimated TEMAH minimum detectable densities as low as ≈2 × 10(12) molecules/cm(3) could be obtained. While this technique was demonstrated specifically for TEMAH delivery and hafnium oxide ALD using TEMAH and water, it should be readily applicable to other metal alkylamide compounds and associated metal oxide and nitride deposition chemistries, assuming similar metal alkylamide molar absorptivity and molecular density in the measurement chamber.

Toward clean and crackless transfer of graphene.

We present the results of a thorough study of wet chemical methods for transferring chemical vapor deposition grown graphene from the metal growth substrate to a device-compatible substrate. On the basis of these results, we have developed a "modified RCA clean" transfer method that has much better control of both contamination and crack formation and does not degrade the quality of the transferred graphene. Using this transfer method, high device yields, up to 97%, with a narrow device performance metrics distribution were achieved. This demonstration addresses an important step toward large-scale graphene-based electronic device applications.