Assessing the Economic Value of Clinical Artificial Intelligence: Challenges and Opportunities.

OBJECTIVES: Clinical artificial intelligence (AI) is a novel technology, and few economic evaluations have focused on it to date. Before its wider implementation, it is important to highlight the aspects of AI that challenge traditional health technology assessment methods. METHODS: We used an existing broad value framework to assess potential ways AI can provide good value for money. We also developed a rubric of how economic evaluations of AI should vary depending on the case of its use. RESULTS: We found that the measurement of core elements of value-health outcomes and cost-are complicated by AI because its generalizability across different populations is often unclear and because its use may necessitate reconfigured clinical processes. Clinicians' productivity may improve when AI is used. If poorly implemented though, AI may also cause clinicians' workload to increase. Some AI has been found to exacerbate health disparities. Nevertheless, AI may promote equity by expanding access to medical care and, when properly trained, providing unbiased diagnoses and prognoses. The approach to assessment of AI should vary based on its use case: AI that creates new clinical possibilities can improve outcomes, but regulation and evidence collection may be difficult; AI that extends clinical expertise can reduce disparities and lower costs but may result in overuse; and AI that automates clinicians' work can improve productivity but may reduce skills. CONCLUSIONS: The potential uses of clinical AI create challenges for health technology assessment methods originally developed for pharmaceuticals and medical devices. Health economists should be prepared to examine data collection and methods used to train AI, as these may impact its future value.

Targeted Ligand-Exchange Chemistry on Cesium Lead Halide Perovskite Quantum Dots for High-Efficiency Photovoltaics.

The ability to manipulate quantum dot (QD) surfaces is foundational to their technological deployment. Surface manipulation of metal halide perovskite (MHP) QDs has proven particularly challenging in comparison to that of more established inorganic materials due to dynamic surface species and low material formation energy; most conventional methods of chemical manipulation targeted at the MHP QD surface will result in transformation or dissolution of the MHP crystal. In previous work, we have demonstrated record-efficiency QD solar cells (QDSCs) based on ligand-exchange procedures that electronically couple MHP QDs yet maintain their nanocrystalline size, which stabilizes the corner-sharing structure of the constituent PbI64- octahedra with optoelectronic properties optimal for solar energy conversion. In this work, we employ a variety of spectroscopic techniques to develop a molecular-level understanding of the MHP QD surface chemistry in this system. We individually target both the anionic (oleate) and cationic (oleylammonium) ligands. We find that atmospheric moisture aids the process by hydrolysis of methyl acetate to generate acetic acid and methanol. Acetic acid then replaces native oleate ligands to yield QD surface-bound acetate and free oleic acid. The native oleylammonium ligands remain throughout this film deposition process and are exchanged during a final treatment step employing smaller cations-namely, formamidinium. This final treatment has a narrow processing window; initial treatment at this stage leads to a more strongly coupled QD regime followed by transformation into a bulk MHP film after longer treatment. These insights provide chemical understanding to the deposition of high-quality, electronically coupled MHP QD films that maintain both quantum confinement and their crystalline phase and attain high photovoltaic performance.

Stereoelectronic Effects on the Binding of Neutral Lewis Bases to CdSe Nanocrystals.

Using 31P nuclear magnetic resonance (NMR) spectroscopy, we monitor the competition between tri- n-butylphosphine (Bu3P) and various amine and phosphine ligands for the surface of chloride terminated CdSe nanocrystals. Distinct 31P NMR signals for free and bound phosphine ligands allow the surface ligand coverage to be measured in phosphine solution. Ligands with a small steric profile achieve higher surface coverages (Bu3P = 0.5 nm-2, Me2P- n-octyl = 2.0 nm-2, NH2Bu = >3 nm-2) and have greater relative binding affinity for the nanocrystal (binding affinity: Me3P > Me2P- n-octyl ∼ Me2P- n-octadecyl > Et3P > Bu3P). Among phosphines, only Bu3P and Me2P- n-octyl support a colloidal dispersion, allowing a relative surface binding affinity ( Krel) to be estimated in that case ( Krel = 3.1). The affinity of the amine ligands is measured by the extent to which they displace Bu3P from the nanocrystals ( Krel: H2NBu ∼ N- n-butylimidazole > 4-ethylpyridine > Bu3P ∼ HNBu2 > Me2NBu > Bu3N). The affinity for the CdSe surface is greatest among soft, basic donors and depends on the number of each ligand that bind. Sterically unencumbered ligands such as imidazole, pyridine, and n-alkylamines can therefore outcompete stronger donors such as alkylphosphines. The influence of repulsive interactions between ligands on the binding affinity is a consequence of the high atom density of binary semiconductor surfaces. The observed behavior is distinct from the self-assembly of straight-chain surfactants on gold and silver where the ligands are commensurate with the underlying lattice and attractive interactions between aliphatic chains strengthen the binding.

Silicon Photoelectrode Thermodynamics and Hydrogen Evolution Kinetics Measured by Intensity-Modulated High-Frequency Resistivity Impedance Spectroscopy.

We present an impedance technique based on light intensity-modulated high-frequency resistivity (IMHFR) that provides a new way to elucidate both the thermodynamics and kinetics in complex semiconductor photoelectrodes. We apply IMHFR to probe electrode interfacial energetics on oxide-modified semiconductor surfaces frequently used to improve the stability and efficiency of photoelectrochemical water splitting systems. Combined with current density-voltage measurements, the technique quantifies the overpotential for proton reduction relative to its thermodynamic potential in Si photocathodes coated with three oxides (SiOx, TiO2, and Al2O3) and a Pt catalyst. In pH 7 electrolyte, the flatband potentials of TiO2- and Al2O3-coated Si electrodes are negative relative to samples with native SiOx, indicating that SiOx is a better protective layer against oxidative electrochemical corrosion than ALD-deposited crystalline TiO2 or Al2O3. Adding a Pt catalyst to SiOx/Si minimizes proton reduction overpotential losses but at the expense of a reduction in available energy characterized by a more negative flatband potential relative to catalyst-free SiOx/Si.

Synthesis and Spectroscopy of Silver-Doped PbSe Quantum Dots.

Electronic impurity doping of bulk semiconductors is an essential component of semiconductor science and technology. Yet there are only a handful of studies demonstrating control of electronic impurities in semiconductor nanocrystals. Here, we studied electronic impurity doping of colloidal PbSe quantum dots (QDs) using a postsynthetic cation exchange reaction in which Pb is exchanged for Ag. We found that varying the concentration of dopants exposed to the as-synthesized PbSe QDs controls the extent of exchange. The electronic impurity doped QDs exhibit the fundamental spectroscopic signatures associated with injecting a free charge carrier into a QD under equilibrium conditions, including a bleach of the first exciton transition and the appearance of a quantum-confined, low-energy intraband absorption feature. Photoelectron spectroscopy confirms that Ag acts as a p-type dopant for PbSe QDs and infrared spectroscopy is consistent with k·p calculations of the size-dependent intraband transition energy. We find that to bleach the first exciton transition by an average of 1 carrier per QD requires that approximately 10% of the Pb be replaced by Ag. We hypothesize that the majority of incorporated Ag remains at the QD surface and does not interact with the core electronic states of the QD. Instead, the excess Ag at the surface promotes the incorporation of <1% Ag into the QD core where it causes p-type doping behavior.

Tight Binding of Carboxylate, Phosphonate, and Carbamate Anions to Stoichiometric CdSe Nanocrystals.

To completely displace the carboxylate surface ligands from cadmium selenide nanocrystals, oleic acid impurities are first removed using dimethylcadmium or diethylzinc. In addition to metal carboxylate and methane coproducts, reactions with CdMe2 produce surface bound methyl groups (δ = 0.4 ppm, 0.04-0.22 nm-2) that photolytically dissociate to methyl radicals and n-doped nanocrystals. Without oleic acid impurities, cadmium carboxylate can be completely displaced from the surface using n-alkylamines (NH2R', R' = n-butyl, n-hexyl, n-octyl) (≤0.01 carboxylates nm-2). Colloidal dispersions of amine bound nanocrystals (CdSe-NH2R') are indefinitely stable at amine concentrations of 0.1 M or higher and slowly aggregate at lower concentrations. Dissociation and evaporation of the amine ligands in 4-ethylpyridine, tri-n-butylphosphine, or molten tri-n-octylphosphine oxide solution results in nanocrystal aggregation. CdSe-NH2R' reacts with oleic acid, n-octadecylphosphonic acid, or carbon dioxide to form surface bound n-alkylammonium oleate, phosphonate, and carbamate ion pairs that bind with greater affinity than primary n-alkylamines. The results indicate that nanocrystal dispersions solely stabilized by neutral donor ligands are relatively unstable compared to those stabilized by adsorbed metal carboxylate or phosphonate complexes or by ion pairs. The challenge of differentiating between the neutral ligand bound form and adsorbed ion pairs is discussed.

Covalent Surface Modification of Gallium Arsenide Photocathodes for Water Splitting in Highly Acidic Electrolyte.

Efficient water splitting using light as the only energy input requires stable semiconductor electrodes with favorable energetics for the water-oxidation and proton-reduction reactions. Strategies to tune electrode potentials using molecular dipoles adsorbed to the semiconductor surface have been pursued for decades but are often based on weak interactions and quickly react to desorb the molecule under conditions relevant to sustained photoelectrolysis. Here, we show that covalent attachment of fluorinated, aromatic molecules to p-GaAs(1 0 0) surfaces can be employed to tune the photocurrent onset potentials of p-GaAs(1 0 0) photocathodes and reduce the external energy required for water splitting. Results indicate that initial photocurrent onset potentials can be shifted by nearly 150 mV in pH -0.5 electrolyte under 1 Sun (1000 W m-2 ) illumination resulting from the covalently bound surface dipole. Though X-ray photoelectron spectroscopy analysis reveals that the covalent molecular dipole attachment is not robust under extended 50 h photoelectrolysis, the modified surface delays arsenic oxide formation that results in a p-GaAs(1 0 0) photoelectrode operating at a sustained photocurrent density of -20.5 mA cm-2 within -0.5 V of the reversible hydrogen electrode.

Proton Reduction Using a Hydrogenase-Modified Nanoporous Black Silicon Photoelectrode.

Metalloenzymes featuring earth-abundant metal-based cores exhibit rates for catalytic processes such as hydrogen evolution comparable to those of noble metals. Realizing these superb catalytic properties in artificial systems is challenging owing to the difficulty of effectively interfacing metalloenzymes with an electrode surface in a manner that supports efficient charge-transfer. Here, we demonstrate that a nanoporous "black" silicon (b-Si) photocathode provides a unique interface for binding an adsorbed [FeFe]-hydrogenase enzyme ([FeFe]-H2ase). The resulting [FeFe]-H2ase/b-Si photoelectrode displays a 280 mV more positive onset potential for hydrogen generation than bare b-Si without hydrogenase, similar to that observed for a b-Si/Pt photoelectrode at the same light intensity. Additionally, we show that this H2ase/b-Si electrode exhibits a turnover frequency of ≥1300 s(-1) and a turnover number above 10(7) and sustains current densities of at least 1 mA/cm(2) based on the actual surface area of the electrode (not the smaller projected geometric area), orders of magnitude greater than that observed for previous enzyme-catalyzed electrodes. While the long-term stability of hydrogenase on the b-Si surface remains too low for practical applications, this work extends the proof-of-concept that biologically derived metalloenzymes can be interfaced with inorganic substrates to support technologically relevant current densities.

All-Inorganic Germanium Nanocrystal Films by Cationic Ligand Exchange.

We introduce a new paradigm for group IV nanocrystal surface chemistry based on room temperature surface activation that enables ionic ligand exchange. Germanium nanocrystals synthesized in a gas-phase plasma reactor are functionalized with labile, cationic alkylammonium ligands rather than with traditional covalently bound groups. We employ Fourier transform infrared and (1)H nuclear magnetic resonance spectroscopies to demonstrate the alkylammonium ligands are freely exchanged on the germanium nanocrystal surface with a variety of cationic ligands, including short inorganic ligands such as ammonium and alkali metal cations. This ionic ligand exchange chemistry is used to demonstrate enhanced transport in germanium nanocrystal films following ligand exchange as well as the first photovoltaic device based on an all-inorganic germanium nanocrystal absorber layer cast from solution. This new ligand chemistry should accelerate progress in utilizing germanium and other group IV nanocrystals for optoelectronic applications.

Electrical transport and grain growth in solution-cast, chloride-terminated cadmium selenide nanocrystal thin films.

We report the evolution of electrical transport and grain size during the sintering of thin films spin-cast from soluble phosphine and amine-bound, chloride-terminated cadmium selenide nanocrystals. Sintering of the nanocrystals occurs in three distinct stages as the annealing temperature is increased: (1) reversible desorption of the organic ligands (≤150 °C), (2) irreversible particle fusion (200-300 °C), and (3) ripening of the grains to >5 nm domains (>200 °C). Grain growth occurs at 200 °C in films with 8 atom % Cl(-), while films with 3 atom % Cl(-) resist growth until 300 °C. Fused nanocrystalline thin films (grain size = 4.5-5.5 nm) on thermally grown silicon dioxide gate dielectrics produce field-effect transistors with electron mobilities as high as 25 cm(2)/(Vs) and on/off ratios of 10(5) with less than 0.5 V hysteresis in threshold voltage without the addition of indium.

Ligand exchange and the stoichiometry of metal chalcogenide nanocrystals: spectroscopic observation of facile metal-carboxylate displacement and binding.

We demonstrate that metal carboxylate complexes (L-M(O2CR)2, R = oleyl, tetradecyl, M = Cd, Pb) are readily displaced from carboxylate-terminated ME nanocrystals (ME = CdSe, CdS, PbSe, PbS) by various Lewis bases (L = tri-n-butylamine, tetrahydrofuran, tetradecanol, N,N-dimethyl-n-butylamine, tri-n-butylphosphine, N,N,N',N'-tetramethylbutylene-1,4-diamine, pyridine, N,N,N',N'-tetramethylethylene-1,2-diamine, n-octylamine). The relative displacement potency is measured by (1)H NMR spectroscopy and depends most strongly on geometric factors such as sterics and chelation, although also on the hard/soft match with the cadmium ion. The results suggest that ligands displace L-M(O2CR)2 by cooperatively complexing the displaced metal ion as well as the nanocrystal. Removal of up to 90% of surface-bound Cd(O2CR)2 from CdSe and CdS nanocrystals decreases the Cd/Se ratio from 1.1 ± 0.06 to 1.0 ± 0.05, broadens the 1S(e)-2S(3/2h) absorption, and decreases the photoluminescence quantum yield (PLQY) from 10% to <1% (CdSe) and from 20% to <1% (CdS). These changes are partially reversed upon rebinding of M(O2CR)2 at room temperature (∼60%) and fully reversed at elevated temperature. A model is proposed in which electron-accepting M(O2CR)2 complexes (Z-type ligands) reversibly bind to nanocrystals, leading to a range of stoichiometries for a given core size. The results demonstrate that nanocrystals lack a single chemical formula, but are instead dynamic structures with concentration-dependent compositions. The importance of these findings to the synthesis and purification of nanocrystals as well as ligand exchange reactions is discussed.

Broadband absorbing bulk heterojunction photovoltaics using low-bandgap solution-processed quantum dots.

We describe bulk heterojunction (BHJ) solar cells containing blends of colloidal PbS nanocrystal quantum dots with several new donor-acceptor conjugated polymers. Using photoinduced absorption spectroscopy we found that blends of PbS quantum dots with one polymer, poly(2,3-didecyl-quinoxaline-5,8-diyl-alt-N-octyldithieno[3,2-b:2',3'-d]pyrrole) (PDTPQx), produce significantly more photoinduced charge than blends of PbS with the other donor-acceptor polymers or with traditionally studied polymers like [2-methoxy-5-(3',7'-dimethyloctyloxy)-para-phenylene vinylene] (MDMO-PPV) and poly(3-hexylthiophene) (P3HT). Photovoltaic devices made with PDTPQx/PbS blends exhibit power conversion efficiencies 10-100 times larger than previously reported BHJ blends made with IR-absorbing quantum dots.

Absence of photoinduced charge transfer in blends of PbSe quantum dots and conjugated polymers.

We use photoluminescence (PL) quenching and photoinduced absorption (PIA) spectroscopy to study charge transfer in bulk heterojunction blends of PbSe quantum dots with the semiconducting polymers poly-3-hexylthiophene (P3HT) and poly[2-methoxy-5-(3',7'-dimethyloctyloxy)-para-phenylene vinylene] (MDMO-PPV). PIA spectra from the PbSe blends are compared to spectra from similar blends of the polymers with phenyl-C(61)-butyric acid methyl ester (PCBM) and blends with CdSe quantum dots. We find that the MDMO-PPV PL is quenched, and the PL lifetime is shortened upon addition of PbSe quantum dots, while the PL of the P3HT is unaffected upon blending. However, for PbSe blends with both polymers, the PIA spectra show very little polaronic signal, suggesting that few, if any, long-lived charges are being produced by photoinduced charge transfer.