High throughput second harmonic generation microscopy accelerating non-centrosymmetric material discovery through megalibraries

Abstract

A method for screening molecular crystal megalibraries for non-centrosymmetric structure can include scanning a substrate comprising a plurality of molecular crystals with a tunable laser, a focusing objective, and a detector, to identify molecular crystals emitting a second harmonic generation (SHG) signal. The method also includes correlating the regions having an SHG signal with elemental composition and optical images to identify compositions of molecular crystals having a non-centrosymmetric crystalline structure. The method can be performed at a plurality of measuring temperatures to identify the Curie temperature of a composition. The method can further include designing a composition with a target Curie temperature.

Description

Docket No. 30938 / 2024-131HIGH THROUGHPUT SECOND HARMONIC GENERATION MICROSCOPY ACCELERATING NON-CENTROSYMMETRIC MATERIAL DISCOVERY THROUGH MEGALIBRARIES CROSS REFERENCE TO RELATED APPLICATION

[0001] The benefit of priority to U.S. Provisional Application No. 63 / 720,463 filed November 14, 2024, is hereby claimed and the disclosure is incorporated herein by reference in its entirety.STATEMENT OF GOVERNMENT SUPPORT

[0002] This invention was made with government support under grant numbers W911 NF-23-1-0285, and W911 NF-23-1-0141 awarded by the Army Research Office and grant number FA9550-22-1-0300 awarded by the Air Force Office of Scientific Research. The government has certain rights in the invention.FIELD

[0003] The disclosure is generally directed to methods of screening the centrosymmetric properties of molecular nanocrystals and more particularly, to methods of screening for center of symmetry a plurality of molecular nanocrystals arranged in nanocrystal megalibraries using a high throughput collection of second harmonic generation signals.BACKGROUND

[0004] Non-centrosymmetric (NC) materials possess properties of interest in modern electronics, optics, and even biomedical devices. For instance, NC materials with high piezoelectricity can convert mechanical energy into electricity with large energy conversion efficiency, providing new avenues for energy harvesting, self-powered sensing, and humanmachine interaction. The small power consumption in switching polarizations in ferroelectric thin films (a type of non-centrosymmetric materials with polar structure) allows for more energy-efficient computation at high-density integration in applications such as the speedy non-volatile memory. Likewise, the interaction of NC crystals with excitable cells and tissues enabled innovation in minimally invasive / non-invasive therapies, one example being the use of piezoelectric nanoparticles for electrostimulation and non-linear optical nanoprobes for in vivo imaging.

[0005] Traditionally, NC material discovery relies on experimental trial and error with some theoretical guidance. For example, molecular halides with asymmetric A-site cations (particularly, the quasi-sphere A site) often form non-centrosymmetric crystals. However, conventional methods produce only one NC material per synthesis, making it timeconsuming to explore the vast compositional space for materials with desirable properties like strong electromechanical coupling. Thus, serial exploration of synthetic parameters isDocket No. 30938 / 2024-131impractical, highlighting the need for high-throughput synthesis and screening methods to efficiently and cost-effectively discover NC materials with exceptional optical and electrical properties, such as high piezoelectricity. In addition, high throughput characterization methods, particularly characterization of composition, structure, and properties, are needed to efficiently characterize large numbers of compositional material variations to identify the composition or composition range having the desired structure and properties for a particular application.SUMMARY

[0006] A method of screening a molecular crystal megalibrary for non-centrosymmetric crystalline structure can include: obtaining an optical image of a substrate including the megalibrary comprising a plurality of molecular crystals with a size of about 50 nm to 5pm and having a compositional gradient of at least one element of the crystal in at least one x and y direction; scanning the substrate with a multiphoton confocal laser scanning microscope including a tunable laser, a focusing objective and a detector; detecting with the detector the second harmonic generation signal; comparing an image including the second harmonic generation signal detected across the substrate to the optical image to identify one or more regions of the optical image in which the second harmonic generation signal was detected; and correlating the one or more regions in which the second harmonic generation signal was detected to compositions of molecular crystals within the regions, thereby identifying compositions having a non-centrosymmetric crystalline structure.

[0007] Scanning the substrate can include dividing the substrate into scanning regions each having a size equal or less than a spot size of a laser when focused on the substrate by the focusing objective and focusing the laser for a scanning time in each region.

[0008] The molecular crystals having a non-centrosymmetric crystalline structure can emit a second harmonic generation signal. The second harmonic generation signal has a frequency equal to two times the frequency of the laser.

[0009] The megalibrary can include at least 1 million crystals per cm2arranged on the substrate.

[0010] Described herein is a method of designing a molecular crystal composition having a target Curie temperature. The method can include: obtaining an optical image of a substrate including a megalibrary having a compositional gradient of at least one element in at least one of x and y direction; bringing the substrate to a first measuring temperature less than the target Curie temperature; detecting a second harmonic generation signal from the substrate at the first measuring temperature using a multiphoton confocal laser scanning microscope including a tunable laser, a focusing objective and a detector and generating anDocket No. 30938 / 2024-131image of the detected signal; repeating one or more times bringing the substrate to a further measuring temperature different from the first measuring temperature and detecting the second harmonic generation signal from the substrate; comparing the images of the detected second harmonic generation signal at the further measuring temperatures and the image of the detected second harmonic generation signal at the first measuring temperature and identifying one or more regions of the images in which the second harmonic generation signal is detected at each of the further measuring temperatures below the target Curie temperature, correlating the identified one or more regions to the optical image; and thereby identifying compositions of crystals having a non-centrosymmetric crystalline structure at the first measuring temperature and the target Curie temperature.

[0011] Each further measuring temperature is an increased temperature incrementally between the first temperature and a final measuring temperature. The final measuring temperature can be the target Curie temperature or higher than the target Curie temperature.

[0012] A method of identifying a Curie temperature for a molecular crystal composition can include providing a substrate including a megalibrary; detecting a second harmonic generation signal from the substrate at a plurality of measuring temperatures using a multiphoton confocal laser scanning microscope including a tunable laser, a focusing objective and a detector and identifying the measurement temperature at which a second harmonic generation signal is not detected from the substrate, thereby finding the Curie temperature of the composition. Detecting the second harmonic generation signal at each measuring temperature can include brining the substrate to the measuring temperature; dividing the substrate into scanning regions, focusing the laser for a scanning time in each region. The megalibrary includes a plurality of molecular crystals having the composition.BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 A is a schematic of the polymer pen lithography process to produce megalibraries of 1 D molecular nanocrystals (left) and models of the resulting 1 D structures (right).

[0014] Figure 1 B is a series of optical (top row) and SEM (bottom row) images of patterned areas and arrays of molecular crystals inside a single megalibrary imaged at increasing magnifications.

[0015] Figure 1C (top) is an experimental XRD pattern of a megalibrary of TMCMCdCh particles and (bottom) a simulated XRD pattern of TMCMCdC molecular crystals.Docket No. 30938 / 2024-131

[0016] Figure 2A is a schematic of an SHG signal measurement process in accordance with the disclosure.

[0017] Figure 2B is a series of SHG response images of the entire megalibrary (left), an individual region (center), and an individual molecular nanocrystal (right).

[0018] Figure 2C is a collection of SHG response spectra recorded at different excitation wavelengths.

[0019] Figure 3 is a schematic of the polymer pen lithography process (right) with combinatorial spray (left).

[0020] Figure 4A shows molecular and crystal structures of TMCMCdCh (top) and TMACdCh (bottom).

[0021] Figure 4B is a series of XRD patterns of TMCMzTMA(i-Z)CdCl3 with varying z values.

[0022] Figure 4C is a dark field optical image of the patterned TMCMzTMA(i.z)CdCl3 molecular megalibrary.

[0023] Figure 4D is a ToF-SIMS mass spectrum of a 500pm x 500pm region of the megalibrary in Figure 4C.

[0024] Figure 4E is a heat map showing the peak intensity of the TMCM / TMA ratio in the entire TMCMzTMA(i.z)CdCl3 megalibrary.

[0025] Figure 5 is an image of the SHG signal of the TMCMzTMA(i.z)CdCl3 megalibrary.

[0026] Figure 6A shows schematic molecular structures of the compounds TMCMCdCh (top) and TMCMCdCIBr2(bottom).

[0027] Figure 6B shows XRD patterns of the TMCM CdClxBr(i.X) series, with varying x values.

[0028] Figure 6C is a dark-field optical image of the patterned TMCM CdClxBr(i_x)molecular megalibrary.

[0029] Figure 6D is a ToF-SIMS mass spectrum of a 500pm x 500pm region of the megalibrary in figure 6C.

[0030] Figure 6E is a heat map showing the peak intensity of the Cl / Br ratio in the entire TMCM CdClxBr(i_X) megalibrary.

[0031] Figure 7A is an SHG signal image of the megalibrary in Figure 6C taken at room temperature.Docket No. 30938 / 2024-131

[0032] Figure 7B is a series of SHG images of the megalibrary in Figure 6C taken at different temperatures as indicated in each panel.

[0033] Figure 70 shows SHG spectra of the TMCMCdCli 8Bri2compound taken at different temperatures (left) and a corresponding SHG intensity vs. temperature graph (right).

[0034] Figure 8 is a schematic of the precursors used in the TMCM CdzPb(i-Z) CI3 megalibrary.

[0035] Figure 9 is a series of XRD patterns of TMCM CdzPb(i-Z) Chwith varying z values.

[0036] Figure 10 is a dark-field optical image of the patterned TMCM CdzPb(i-Z) C molecular megalibrary.

[0037] Figure 11 is a ToF-SIMS mass spectrum of a 500pm x 500pm region of the megalibrary in figure 10.

[0038] Figure 12 is a heat map showing the peak intensity of the Cl / Br ratio in the entire TMCM CdzPb(i-Z) C megalibrary.

[0039] Figure 13 is an SHG signal image of the megalibrary in Figure 10.DETAILED DESCRIPTION

[0040] The advent of nanoparticle megalibraries with millions of positionally encoded nanomaterials on a cm-scale chip, has been made possible by massively parallel scanning probe synthesis tools. For instance, extensions of Dip Pen Nanolithography (DPN) has significantly accelerated the materials discovery process. By integrating with a spray inking method, the 2D scanning probes can be inked with concentration gradients of precursors and delivered the inks to the substrates to form a megalibrary of compositionally distinct crystals, paving the way for high throughput synthesis. Methods of the disclosure utilize the integration of megalibrary synthesis and second harmonic generation (SHG) microscopy to provide a high-throughput methodology for synthesis of and screening for non-centrosymmetric materials with unique optical and electric properties. Further, the Curie temperature (Tc)-composition relationship of a megalibrary can be investigated by performing SGH scans at different temperatures using methods in accordance with the disclosure.

[0041] The method in accordance with the disclosure can advantageously be used for one or more of (1) identifying compositions having non-centrosymmetric structure (i.e., discovering new non-centrosymmetric materials); (2) investigating the composition-curie temperature (Tc) relationship thus discovering new high-Tc materials, (3) identifyingDocket No. 30938 / 2024-131compositions near morphotropic / polymorphic phase boundaries where significantly enhanced piezoelectric and dielectric properties can be found thus discovering materials with excellent piezoelectric and dielectric properties, and / or (4) discovering materials with strong second harmonic generation (SHG) response for laser applications.

[0042] The methods disclosed herein can be applied to molecular crystal materials (e.g., biomolecular crystals, polymeric crystalline materials, metal organic compounds, and crystals of small organic molecules). The methods of the disclosure can be utilized in the materials informatics field, where large data sets can empower machine learning and Al algorithms to identify important and non-intuitive relationships between composition, structure, and properties.

[0043] As used herein, the term “non-centrosymmetric material” refers to a crystalline material that lacks an inversion center. For example, non-centrosymmetric materials include those having one of the following crystallographic point groups (in international notation): 1 , 2, m, 222, mm2, 4, ~4, 422, 4mm, "42m, 3, 32, 3m, 6, "6, 622, 6mm, "6m2, 23, 432 or"43m.

[0044] Second harmonic generation is a nonlinear optical phenomenon, which is only produced in materials with non-centrosymmetric structures and is not present in centrosymmetric materials with inversion symmetry. The second harmonic generation signal has a frequency that is equal to two times the frequency of the laser. In methods of the disclosure, a signal can be detected from second harmonic generation of non-centrosymmetric materials, while no signal will be detected for centrosymmetric materials in the megalibrary. This can enable rapid detection of non-centrosymmetric material compositions.

[0045] Methods of screening a molecular crystal megalibrary for non-centrosymmetric crystalline structures include obtaining an optical image of the substrate comprising the megalibrary. The megalibrary is formed having a known compositional gradient. The optical image can be obtained using any known instruments and methods. The optical image can be correlated to the known compositional gradient. The megalibrary can include a compositional gradient of at least one element of the molecular crystal in at least one x and y direction. For example, the molecular crystals in one corner of the megalibrary can be chlorine rich-bromine deficient, while those on the diagonally opposite corner can be bromine rich-chloride deficient.

[0046] A method of screening a molecular crystal megalibrary further includes scanning the substrate with a multiphoton confocal laser scanning microscope. The microscope includes, at a minimum, an adjustable stage, a tunable laser, a focusing objective, and a detector. The focusing objective focuses the laser to a diffraction-limited spot on theDocket No. 30938 / 2024-131substrate. The substrate is divided into scanning regions having a size based on the size of the focusing objective. The laser is then focused on each scanning region for a scanning time. The molecular crystals having a non-centrosymmetric crystalline structure emit a second harmonic generation signal that is detected by the detector. An image of the detected second harmonic generation signal across the substrate can be generated and then compared to the optical image to identify one or more regions of the optical image in which the second harmonic generation signal was detected. These one or more regions can then be correlated to the composition of the molecular crystals based on the known compositional gradient used in forming the megalibrary. As a result, a range of compositions having a non-centrosymmetric crystalline structure can be identified.

[0047] Methods of the disclosure can also be used in identifying and / or analyzing a Curie temperature of molecular crystals. This can be useful for designing materials having a target Curie temperature, and / or identifying a Curie temperature of a given composition. The Curie temperature is the temperature at which a polarized non-centrosymmetric material, e.g., a piezoelectric material, transitions from a polarized state to a non-polarized state, thereby losing its piezoelectric properties. Knowing the Curie temperature of a material can be advantageous in selecting the operating conditions of a device containing the material. For example, a piezoelectric can be used as a sensing material in a pressure fluctuation or vibration sensor, the sensor would be less reliable at temperatures close or higher than the Curie temperature of the sensing material as a change in polarization state will negate the piezoelectric effect used in the sensing function.

[0048] Methods of designing a composition of a molecular crystal to have a target Curie temperature include repeated scanning of the substrate at different temperature for identification of second harmonic generation signals. Scanning can be done with a first temperature and increasing or decreasing temperatures for subsequent measurements. For example, scanning can start at a first temperature that is below the target Curie temperature and incrementally increased to and optionally beyond the Curie temperature. The method can include obtaining an optical image of a substrate comprising a molecular crystal megalibrary that has a plurality of molecular crystals with a compositional gradient across the substrate. The substrate is scanned in individual scanning regions at a first measuring temperature using a multiphoton confocal laser, where those molecular crystals having a non-centrosymmetric structure will generate a second harmonic generation signal that can be detected by the detector. The individual scanning regions are then repeatedly scanned at incrementally increased temperatures until at least the one of the measuring temperatures is at the target Curie temperature. Additionally, measurements at temperatures higher than the target Curie temperature can optionally be performed. Those molecular crystals having theDocket No. 30938 / 2024-131target Curie temperature will produce second harmonic generation signals at temperatures below the Curie temperature but will no longer produce the second harmonic generation signal at the Curie temperature. This can be identified by images generated from the detected signals at each measuring temperature. A comparison of those images can allow for identification of where one or more regions exhibits a transition from a detected signal to no signal detection at a given measuring temperature. Those regions in which the transition is observed at the target Curie temperature can be compared to the optical image, through which the regions can be correlated to compositions of molecular crystals. Thus, a design of one or more compositions of molecular crystals having a target Curie temperature can be obtained.

[0049] Methods of the disclosure can also be useful in identifying a Curie temperature of a single composition. The method can include bringing a substrate having a plurality of molecular crystals having the compositions to a first measuring temperature. The first measuring temperature can be selected to be a temperature at which the composition is or is believed to be non-centrosymmetric and, thus, will generate a second harmonic generation signal. The method can then include scanning the substrate in individual scanning regions with a multiphoton confocal laser scanning microscope and detecting for a second harmonic generation signal at each of the measuring temperatures. The measuring temperatures can be incrementally increased, and the detection of a second harmonic generation signal process can be repeated until the second harmonic generation signal is no longer detected. The Curie temperature will be the lowest temperature at which the second harmonic generation signal is no longer detected.

[0050] In the methods for screening or identifying a Curie temperature, the method includes scanning for a second harmonic generation signal at different measuring temperatures. In any of the methods, the measuring temperatures can be increased temperature incrementally between the first temperature and the final measuring temperature. In methods of screening for a composition having a target Curie temperature, the final measuring temperature can be the target Curie temperature or a temperature greater than the target Curie temperature. In methods of identifying a Curie temperature of a composition, the final measuring temperature can be a temperature at which the second harmonic generation signal is no longer detected or a temperature greater than a first instance of when the second harmonic generation signal is no longer detected. Any increments of temperature can be used for increasing between the first measuring temperature and the final measuring temperature. For example, the increment can be about 0.5 °C to about 10 °C. For example, increments of about 5QC can be used.Docket No. 30938 / 2024-131

[0051] In each of the methods of screening for or identifying a Curie temperature, the substrate can be brough to the measuring temperature using any known methods. For example, the substrate can be placed on a temperature-controlled stage and heated between scans until the desired measuring temperature is achieved.

[0052] Identifying the Curie temperature of a composition or compositions having a target Curie temperature can include displaying the second harmonic generation signals detected at the plurality of measuring temperatures as images and comparing the images to identify the temperature at which the signal transitions from being visible to not visible. Alternatively or additionally, an intensity of the signal detected from the substrate can be graphed as a function of temperature to identifying the temperature at which a drop in signal occurs, thereby identifying the Curie temperature. Still further or alternatively, the second harmonic generation signal detected at the plurality of measuring temperatures can be presented as intensity plots, showing signal intensity relative to regions of the substrate and the intensity plots can be compared or overlaid to identify the regions and / or temperatures at which the signal intensity transitions to zero or near zero, thereby identifying the Curie temperature and / or compositions having a target Curie temperature.

[0053] In any of the methods of the disclosure, the megalibrary includes a plurality of molecular crystals that can range in size from about 50 nm to about 5pm as measured from electron microscopy images. For example, the molecular crystals can have a size of about 50 nm, 60 nm, 75 nm, 100 nm, 125 nm, 150 nm, 200 nm, 250 nm, 300 nm, 350 nm, 400 nm, 450 nm, 500 nm, 600 nm, 700 nm, 800 nm, 900 nm, 1 pm, 1 ,5pm, 2pm, 3pm, 4pm, 5pm, or any values therebetween or ranges defined by such values. The megalibrary can be designed with one or both of composition and feature size gradients across the substrate. For example, the molecular crystals of the megalibrary can have the same composition but vary in feature size across the substrate. For example, the molecular crystals of the megalibrary can have a compositional gradient of at least one element in the x and / or y directions and have the same or different features sizes across the substrate. Still further, the molecular crystals can have the same composition and same feature size across the substrate.

[0054] According to the disclosure megalibraries of molecular crystals can include millions of crystals. For example, a megalibrary can have at least one million crystals per cm2. For example, a megalibrary can have about four million, about five million, about six million, about seven million, about eight million, or about 10 million crystals in a 2 cm x 2 cm area.

[0055] Molecular crystals megalibraries can be prepared using any known methods. For example, polymer pen lithography (PPL) can be used to deposit megalibraries. Depositing aDocket No. 30938 / 2024-131megalibrary using PPL can include spin-coating or spray-coating a pen array with a precursor ink, contacting the inked pen array with a solid substrate at a velocity (e.g., 30 pm / s) until a contact force is reached (e.g., about 1000 mN) and maintained for a period (e.g., ~1 s), retracting the substrate and moving the pen array to a second region of the substrate to continue patterning. The pen array can be inked with different inks, for example to achieve a gradient of compositions. Alternatively, the pen array can be spray coated with different inks, for example a first ink on one corner and a second ink at the diagonally opposite corner to achieve a composition gradient. The composition gradient can be from 100% to 0% between adjacent corners of the substrate or any values therebetween or ranges defined by such values. Any methods of coating the tips arrays with the precursor ink can be used herein.

[0056] Any molecular crystal structures can be provided in the megalibrary. Common molecular crystals can include solids resulting from the crystallization or assembling of diatomic and / or polyatomic molecules bound in a periodic array by relatively weak bonds like Van Deer Waals, London and halogen bonding forces and any other molecular interaction. Similarly, to atomic crystals, molecular crystals can exist in different spatial arrangements with the same composition (i.e., polymorphism). However, specific spatial arrangements can be difficult to predict in molecular crystals as polymorphs may have similar conformational energies. Common molecular crystals can include non-polar molecules, small organic molecules (e.g., methane), metal-organic compounds, planar aromatic molecules (e.g., benzene), biopolymers, proteins, and any other molecule with weak intermolecular forces.

[0057] For example, the megalibrary of molecular nanocrystals can have a formula A(Cd)(ClyBr(3-y)), where “A” is an organic cation. For example, the organic cation can be trimethyl chloromethyl ammonium. The composition profiles, including the Cl / Br ratios can be analyzed using ToF-SIMS and the SHG signal can be measured using a multiphoton microscope with a controlled temperature stage. The SHG signal can be measured at different temperatures, the temperature at which the SHG signal disappears for a particular composition is the Curie temperature for that particular Cl / Br ratio.

[0058] In any of the methods of the disclosure, the second harmonic generation signal is detected using a multiphoton confocal microscope. The multiphoton confocal microscope includes a tunable laser that applies multiphoton excitation to the substrate. The tunable laser is focused on the substrate using a focusing objective. Different equipment may have different or selectable focusing objective sizes. The scanning of the megalibrary is done in incremental scanning regions to accommodate a given focusing size of the focusing objective. The microscope further includes a detector for detecting the optical response ofDocket No. 30938 / 2024-131the substrate upon scanning. The detector is tuned for detection of wavelengths representing the second harmonic generation signal.

[0059] Focusing the laser can include recording the z-coordinate of each scanning region and using the z-coordinate to adjust the distance between the laser and the substrate to compensate for variations in focal depth.

[0060] The tunable laser can have a wavelength of about 700 nm to about 1300 nm, about 700 nm to about 1100 nm, about 800 nm to about 1200 nm, about 900 nm to about 1200 nm, about 900 nm to about 1100 nm, or any values therebetween or ranges defined by such values.

[0061] The detector in the multiphoton confocal laser scanning microscope can be configured to detect light at a wavelength corresponding to half the wavelength of the light emitted by the tunable laser.

[0062] The microscope can further include or be in electronic communication with one or more processors for processing the detected signal. The processor can process the detected signal in any known way, including generating images, generating graphs showing signal detection and / or signal intensity as a function of scanning region, or intensity plots showing signal intensity across the substrate. The processor or other processing software can also be used for comparison of images, such as comparison of the optical image and the signal image to identify regions of composition having a non-centrosymmetric structure and / or comparison of multiple signal images at different temperatures to identify a Curie temperature.

[0063] In any of the methods of the disclosure, the laser scans the megalibrary in individual scanning regions. The megalibrary is divided into scanning regions having a size based on the focusing objective used. The magnifying power of the objective can be selected based on the size of the nanocrystals to be resolved by the objective, balanced against the time it takes to scan the entire megalibrary. For example, for nanoparticles having a size of 2 pm or less, it was observed that a 20x objective can allow for the individual nanoparticles to be clearly resolved while allowing for a reasonable scanning time. Higher magnification can be used for such particles with good resolution of the imaged particles, but the scanning time increases, as the higher magnification results in smaller scanning region sizes. At lower objective magnification such as 10x, it was observed that the particles having a size of 2 pm or less were not clear in the image, and thus, it can be concluded that such magnification is not sufficient for this particle size. For megalibriaries having large particles, lower objective magnifying power may be sufficient for clear resolution of the particles, and reduction of the magnifying power can result in improved scanningDocket No. 30938 / 2024-131speed. Thus, the selected objective magnification power can be made balancing the need for clearly resolving the particles to be imaged, while maintaining as large a scanning region size as possible to minimize scanning time. For example, scanning regions can be in a range of about 300pm by 300pm when a 20x objective is used in the multiphoton confocal microscope. Each scanning region is sized to ensure that the laser is focused on the scanning region size. The laser is then moved across the substrate for scanning in each scanning region and detection of a signal, if any, generated in the scanning region. The megalibrary can be divided such that each scanning region is a discrete portion of the megalibrary and are adjacent to one another without overlapping. Alternatively, the megalibrary can be divided into scanning regions such that a portion of adjacent scanning regions overlap and are part of each adjacent scanning region. For example, the scanning regions can be divided such that they have a 0% to 20% overlap, 5% to 10% overlap, or 1% to 15% overlap, or any overlap having a value or range between and of such values.

[0064] Methods of the disclosure were advantageously used to identify compositions that were previously unknown. In particular, molecular crystal compositions having non-centrosymmetric structures are difficult to predict due to the complex molecular interaction that can drive these compositions to crystalize in a number of different structures, including centro and non-centrosymmetric polymorphs. In fully miscible binary systems, for example, compositions with potentially high piezoelectric properties can exist, however finding the precise compositional ranges where the compounds crystallize in non-centrosymmetric phases can be challenging and usually require extensive experimentation and testing on millions of composition combinations. Prior to the methods of the disclosure, there was no known method for rapidly testing a vast number of compositions for non-centrosymmetric properties. Methods of the disclosure, however, allow for rapid production of millions of nanoparticles forming a megalibrary having particles of various composition combinations and rapid screening of the megalibrary for non-centrosymmetric properties, thereby leading to a faster discovery of the phases of interest.

[0065] Molecular crystals newly identified by the methods disclosed herein can be of the following formula TMCMZTMA(i-Z)Cd C ; where z can have a value in a range of about 0.4 to about 1. For example, z can be about 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1 .0 or any values therebetween or ranges defined by such values.

[0066] Molecular crystals newly identified by the method disclosed herein can be of the formula TMCM CdzPb(i-Z) Ch; z can have a value in a range of about 0.5 to about 1. For example, z can be about 0.5, 0.6, 0.7, 0.8, 0.9, 1 .0 or any values therebetween or ranges defined by such values.Docket No. 30938 / 2024-131

[0067] The molecular crystals can be characterized by a point group selected from the group consisting of 1, 2, m, 222, mm2, 4, ~4, 422, 4mm, "42m, 3, 32, 3m, 6, "6, 622, 6mm, "6m2, 23, 432 or"43m.EXAMPLES

[0068] The following examples are provided for illustration and are not intended to limit the scope of the invention.

[0069] In general, megalibraries of molecular crystals were prepared using a polymer pen lithography method (PPL) as illustrated in Figure 1 A (single composition) and Figure 3 (combinatorial spray inking). For single-composition megalibraries (e.g., TMCMCdC , TMACdCh, TMCMCdCIBr2), a pen array was spin-coated with the appropriate precursor ink at a spin speed of 3,000 rpm for 1 min. For (TMAzTMCM(i-Z))CdCl3 and (TMCM)Cd(ClxBr(3-x)) megalibraries, a combinatorial spray-inking process was conducted for gradient composition tuning for the inked pen array. The pen array was secured under a spray gun with a nozzle. The nozzle was centered over one corner of the exposed area by moving the pen array location. A spray controller was programmed to deliver 4 pL of ink at a rate of 3 mL / min and a pressure of 0.5 bar. After spraying two diagonal corners (e.g., TMCMCdCh and TMCMCdCIBr2), gradient composition tuning was achieved for the inked pen array along the diagonal. To create molecular crystal megalibraries with a perovskite-like composition (ABX3), the inked pen array was brought into contact with a solid substrate (e.g., silicon) through instruments known in the art (e.g., TERA-print M-series lithography) at a specific velocity (e.g., 30 pm / s) until a contact force of about 1000 mN was obtained and maintained for a period (e.g., ~1 s), followed by retraction of the substrate and continuation of the patterning.

[0070] In general, composition profiles of the megalibraries were measured using Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). For example, in the (TMCM)Cd(ClxBr(3-X)) megalibrary, the mass spectra generated by the ToF-SIMS instrument were analyzed, and the peak intensities of Cl and Br were compared to understand the relative abundance of the anions. The Cl / Br peak intensity ratios for the whole megalibrary were mapped by scanning the entire megalibrary. The Cl / Br peak intensity and ratios of known compounds, TMCMCdCI275Br025, TMCMCdCI25Br05, TMCMCdCI225Br075.TMCMCdCI2Br, TMCMCdCh sBn 5, TMCMCdCh2sBri 75 and TMCMCdCIBr2, were measured and used to build a calibration curve. The calibration curve was then used to map the composition profile of the megalibrary.

[0071] Second harmonic generation (SHG) measurements were carried out using a Leica DiveB Sp8 multiphoton confocal laser scanning microscope. The wavelength of theDocket No. 30938 / 2024-131excitation light was selected using an Insight tunable laser (700-1300 nm). The laser was set to emit a light beam (i.e., excitation light) with a wavelength of 1064 nm, while the microscope detector was configured to detect light at 532 nm with a bandwidth of 10 nm. A schematic of the measurement setup is shown in Figure 2A. Scanning of large areas was enabled by using a motorized stage to move the sample relative to the fixed multiphoton laser under a high magnification objective of 20x. This allowed the acquisition of the SHG response over the entire megalibrary while maintaining high resolution and imaging quality. The programmable-focusing capabilities were utilized to maintain optimal focus throughout the entire area of megalibrary. The system automatically adjusted the focus at different positions based on pre-programmed settings to compensate for variations in focal depth. Example 1: One-dimensional Molecular Crystal Megalibraries

[0072] A megalibrary of TMCM CdCh molecular crystals was prepared using a PPL method (Fig. 1 A). In a typical experiment, a mixture of TMCM-CI and CdCh precursors were dissolved in organic solvent (e.g., dimethyl sulfoxide (DMSO) to yield the precursor ink. Polymer pen arrays consisting of thousands of polydimethylsiloxane (PDMS) pyramids (10,000 pens per cm2) were fabricated on glass substrates and then treated with oxygen plasma. The precursor ink was spin-coated onto the treated polymer pen arrays, nanoreactor droplets of the precursor ink were deposited form the pens upon contact with a substrate. For this example, a hydrophobic conductive silicon substrate was used.

[0073] A density of approximately 1 million nanocrystals per cm2was achieved (Fig. 1 B). The as-synthesized nanocrystals revealed well-faceted morphology, as characterized by scanning electron microscopy (SEM), and shown in Figure 1B. Energy-dispersive x-ray spectroscopy (EDS) elemental mapping showed a uniform distribution of C, N, Cd and Cl elements in an individual crystal. An X-ray diffraction (XRD) pattern of the large-scale nanoarrays was in good agreement with the simulated standard pattern for TMCMCdCh (Fig. 1C).Example 2: Measurement of the Non-Linear Optical Response of Megalibraries.

[0074] SHG is a nonlinear optical phenomenon only allowed in materials with non-centrosymmetric structures, materials with inversion symmetry (i.e., centrosymmetric) do not present SHG. To measure the SHG response of the TMCMCdCh megalibrary, the multiphoton laser was set to emit at a wavelength of 1064 nm, while the detector was configured to detect light at 532 nm with a bandwidth of 10 nm. Images of the entire TMCMCdCh megalibrary were taken using a motorized stage to move the sample relative to the fixed multiphoton laser under a high magnification objective of 20x (Fig. 2B). The focus at different regions was automatically adjusted based on pre-programmed settings toDocket No. 30938 / 2024-131compensate for variations in focal depth. The SHG response of the TMCMCdCh was due to its crystallization in a non-centrosymmetric structure (Space group: Cc, Point group: m). Notably, the SHG response of individual nanocrystals in the array was detected with high resolution. To verify the measured response was due to SHG rather than other optical phenomena, an individual nanocrystal was excited with various wavelengths spanning from 950 to 1250 nm. Expected peak shifts from 475 to 625 nm in output wavelengths were detected in spectra of the optical response emitted by the sample (Fig. 2C), precisely half the excitation wavelength, indicating robust SHG signals.Example 3: Combinatorial Megalibraries for High Throughput Synthesis

[0075] Megalibraries allow for the high-throughput synthesis of millions of versions of molecular crystals. Combinatorial spray-inking was used to deliberately control the compositions and volumes of inks on each tip in the pen arrays. The spray-inking process provided a gradient distribution of each precursor ink and allowed for the mixing of multiple types of precursor inks onto tips in such a way that information about ink composition and pen location can be correlated (Fig. 3). In this example, two different precursor inks were sprayed on diagonally opposite corners of a pen array to lead to a composition gradient (Fig.3, left panel). The first ink was prepared by dissolving TMCM-CI and CdCh in DMSO and the second by dissolving TMA-CI and CdCh in DMSO. The pen array was then used to deliver the inks to the substrates to form a megalibrary of crystals with individually distinct composition (Fig. 3, right panel).Example 4: Non-centrosymmetric TMCMzTMA(i-Z)CdCl3 Megalibrary.

[0076] A megalibrary with a varying “A” cation components was exemplified by mixing TMCM CdCh with TMA CdCh (Fig. 4A). Due to the good miscibility of TMCM and TMA cations, mixing varying amounts of TMCM-CdCh and TMA-CdCh produced single-phase XRD patterns without extra peaks from additional phases; the peak intensity changed gradually from pure TMCM-CdCh to pure TMA-CdCh (Fig. 4B). For example, the TMCM CdC characteristic peaks at 10.91Qand 11.24- shifted and almost merged into a single peak with increasing amounts of TMA CdCh. A similar effect was observed for the peaks at 18.83Qand 19.36Q. The TMCM CdCh and TMA CdCh precursors were dissolved in DMSO to form the patterning inks. The inks were sprayed centered on the diagonal corners of a pen array and the inked pens used to print the TMCMzTMA(i.z)CdCh megalibrary.Docket No. 30938 / 2024-131

[0077] Dark-field optical images of the megalibrary showed that the patterned nanoarrays were well defined and relatively uniform with an almost full coverage of the patterning area (Fig. 4C).

[0078] ToF-SIMS was used to measure the mass spectra of characteristic molecular species (TMA+: (CH3)4 N+ and TMCM+: (CH3)3(CH2CI) N+). The peak intensities of TMA+ and TMCM+ species (Fig. 4D) were analyzed to understand the relative abundance of different “A” cations. The TMCM+ / TMA+ peak intensity ratios of different regions (10 regions in total, each having a size of 1 ,2mm x 1.2 mm) in the whole megalibrary were then mapped, which showed clear concentration gradients of TMCM and TMA that matched what was expected from the spraying pattern (Fig. 4C and 4E). A calibration curve correlating the TMCM+ / TMA+ peak intensity ratio with the actual concentrations of TMCM and TMA species was established by measuring the ratios in a series of mixed materials with known compositions. This allowed for the conversion of intensity ratios into actual compositions. Accurate composition mapping for each area provided a basis for studying the compositionproperty relationship of the megalibrary.

[0079] The non-linear optical response of the TMCMzTMA(i-Z)CdCI3megalibrary was characterized by recording the SHG signal using a confocal microscope scanning the entire area of the megalibrary and compared with the dark-field optical microscope image (Fig. 4C and 5). Unlike the minimal difference seen in the dark-field optical image (Fig. 4C), a clear phase boundary separating non-centrosymmetric and centrosymmetric crystals was distinctly observed in the SHG image (Fig. 5). On the left side of the boundary, all patterned crystals showed a strong SHG response, while those on the right exhibited no SHG signal. Based on the composition profile in Figure 4D, this boundary corresponds to a TMCM / TMA intensity ratio of approximately 1.7, equating to a composition near TMCMo / TMAoeCdC . Thus, it was determined that a TMA concentration below 60% favored the formation of non-centrosymmetric structures, while concentrations above 60% led to centrosymmetric structures. Since non-centrosymmetric TMCM-based structures exhibit piezoelectricity, the accuracy of identifying these compositions was validated using PFM characterization, which aligned well with the SHG imaging results.Example 5: Tc-Composition Measurements in a TMCMCdClxBr(3.X) Megalibrary.

[0080] A TMCMCdClxBr(3-X) megalibrary containing two different “X” anions (Fig. 6A) was prepared to demonstrate the capabilities of temperature controlled SHG microscopy to characterize the Curie transition of materials. XRD patterns revealed a good mixing of Cl and Br (Fig. 6B), with gradual merging of peaks at higher concentrations of Br anions. The TMCMCdClxBr(3.X) megalibrary was prepared by spraying solutions of TMCMCdC in DMSODocket No. 30938 / 2024-131and TMCMCdBr2CI in DMSO centered on top of two corners of the diagonal of a pen array and patterning the inks using the inked pen array. A dark-field optical image of the resulting megalibrary showed that the nanoarrays were well patterned (Fig. 6C). The composition profile of the megalibrary was identified through ToF-SIMS measuring and analyzing the peak intensities ion species Cl(35)- and Br (79)- (Fig. 6D). The Cl- / Br- peak intensity ratios of the ten different regions (each having a size of 1 ,2mm x 1.2 mm) in the whole megalibrary were then mapped, which showed clear concentration gradients of Cl- and Br-matching the spraying pattern (Fig. 6E). A calibration curve connecting the peak intensity ratio and actual composition in TMCMCdClxBr(3-x) was obtained by measuring the Cl / Br ratios in a series of mixed materials with known compositions.

[0081] The non-linear optical responses of the entire TMCMCdClxBr(3-x) megalibrary was characterized by scanning SHG microscopy at different temperatures and compared with the dark-field optical microscope image. The room temperature SHG image (Fig. 7A) showed uniform response throughout the megalibrary, indicating all structures were non-centrosymmetric. However, when the megalibrary was heated using a temperature-controllable stage, differences in SHG response due to varying compositions started to appear. As shown in Figure 7B, at 60°C the SHG response in the bottom-left corner, corresponding to the Br-rich region, began to decrease more rapidly than in other areas. Further heating led to a gradual disappearance of the SHG response, progressing from the bottom-left to the top-right corner. By 90°C, only a small region on the top-right, corresponding to the Cl-rich area exhibited detectable SHG response. Since the Curie temperature marks the transition of a piezoelectric material from a polarized to a nonpolarized state, the temperature at which SHG signal disappears indicates the Curie temperature.

[0082] The capability of investigating the Curie temperature-composition relationship was used to design a material with a specific Curie temperature based on the Curie temperaturecomposition relationship learned from imaging the TMCMCdClxBr(3-X) megalibrary. A material with Curie temperature of about 80°C was identified as having a Cl / Br mass peak intensity around 3.3 according to ToF-SIMS. TMCMCdCli3Bri2, a material with a Cl / Br mass ratio of 3.3, was prepared in bulk and analyzed for SHG at different temperatures. A small gradual decrease in SHG signal in the room temperature to about 60°C range and a sharp extinguishment of SHG response at around 80°C were observed (Fig. 7C), indicating the precise Curie temperature-composition relationship uncovered through the megalibrary synthesis and SHG scanning microscopy.

[0083] Without intending to be bound by theory, it is believed that larger concentrations of Br in the TMCMCdClxBr(3-X) system decreases the Curie temperature, an effect that can beDocket No. 30938 / 2024-131due to a weaker binding energy of Cd and Br compared with the binding energy of Cd and Cl.Example 6: Non-centrosymmetricl'MCMCdzPb^-z) C Megalibrary.

[0084] A megalibrary with a varying metal component (i.e., Cd and Pb) was exemplified by mixing TMCMCdCh with TMCM-CI and PbCh in DMSO (Fig. 8). For the entire composition range, single-phase XRD patterns without extra peaks from additional phases were observed; the peak intensity changing gradually from pure TMCMCdCh to TMCM PbCh (Fig. 9). The TMCMCdCh and TMCMPbCh precursors were dissolved in DMSO to form the patterning inks. The inks were sprayed centered on the diagonal corners of a pen array and the inked pens used to print the TMCMCdzPb(i-Z) Ch megalibrary.

[0085] Dark-field optical images of the megalibrary showed that the patterned nanoarrays were well defined and relatively uniform with an almost full coverage of the patterning area (Fig. 10).

[0086] ToF-SIMS was used to measure the mass spectra of characteristic molecular species CdCh-and PbCh-. The peak intensities of CdCh and PbCh species (Fig. 11) were analyzed to understand the relative abundance of the different metal ions. The CdCh I PbCh peak intensity ratios of ten different regions (1 ,2mm x 1 ,2mm each) in the whole megalibrary were then mapped, which showed clear concentration gradients of Cd and Pb that matched what was expected from the spraying pattern (Fig. 10 and Fig.12). A calibration curve correlating the CdCh I PbCh peak intensity ratio with the actual concentrations of Cd and Pb species was established by measuring the ratios in a series of mixed materials with known compositions. This allowed for the conversion of intensity ratios into actual compositions.

[0087] The non-linear optical response of the TMCM CdzPb(i-Z) Ch megalibrary was characterized by recording the SHG signal using a confocal microscope scanning the entire area of the megalibrary (Fig. 13) and compared with the dark-field optical microscope image (Fig. 10). Unlike the minimal difference seen in the dark-field optical image (Fig. 10), a clear phase boundary separating non-centrosymmetric and centrosymmetric crystals was distinctly observed in the SHG image (Fig. 13). On the right side of the boundary, all patterned crystals showed a strong SHG response, while those on the left exhibited no SHG signal. Based on the composition profile in Figure 12, this boundary corresponds to a Cd / Pb intensity ratio of approximately 1 , equating to a composition near TMCM CdosPbos Ch. Thus, a Cd concentration above 50% was observed to favor the formation of non-centrosymmetric structures, while concentrations below 50% led to centrosymmetric structures. Since non-centrosymmetric CdPb-based structures exhibit piezoelectricity, theDocket No. 30938 / 2024-131accuracy of identifying these compositions was validated using PFM characterization, which aligned well with the SHG imaging results.

[0088] The foregoing description is given for clearness of understanding only, and no unnecessary limitations should be understood therefrom, as modifications within the scope of the disclosure may be apparent to those having ordinary skill in the art.

[0089] Throughout the specification, where the compounds, compositions, methods, and / or processes are described as including components, steps, or materials, it is contemplated that the compounds, compositions, methods, and / or processes can also comprise, consist essentially of, or consist of any combination of the recited components or materials, unless described otherwise. Component concentrations can be expressed in terms of weight concentrations, unless specifically indicated otherwise. Combinations of components are contemplated to include homogeneous and / or heterogeneous mixtures, as would be understood by a person of ordinary skill in the art in view of the foregoing disclosure.References[1] S. Das, Y. Tang, Z. Hong, M. Gongalves, M. McCarter, C. Klewe, K. Nguyen, F. Gomez-Ortiz, P. Shafer, E. Arenholz, Nature 2019, 568, 368.[2] A. I. Khan, A. Keshavarzi, S. Datta, Nat. Electron. 2020, 3, 588.[3] K. Kapat, Q. T. Shubhra, M. Zhou, S. Leeuwenburgh, Adv. Funct. Mater. 2020, 30, 1909045.[4] I. Abdelwahab, B. Tilmann, Y. Wu, D. Giovanni, I. Verzhbitskiy, M. Zhu, R. Berte, F. Xuan, L. d. S. Menezes, G. Eda, Nat. Photonics 2022, 16, 644.[5] W. Wu, Z. L. Wang, Nat. Rev. Mater. 2016, 1 , 16031.[6] Y. S. Choi, S. K. Kim, M. Smith, F. Williams, M. E. Vickers, J. A. Elliott, S. Kar-Narayan, Sci. Adv. 2020, 6, eaay5065.[7] Z. L. Wang, J. Song, Science 2006, 312, 242.[8] X. Wang, Nano Energy2012, 1, 13.[9] J. Y. Park, D. H. Choe, D. H. Lee, G. T. Yu, K. Yang, S. H. Kim, G. H. Park, S. G. Nam, H. J. Lee, S. Jo, Adv. Mater. 2023, 35, 2204904.

[0010] K.-H. Kim, I. Karpov, R. H. Olsson III, D. Jariwala, Nat. Nanotechnol. 2023, 18, 422.

[0011] D. Zhang, P. Schoenherr, P. Sharma, J. Seidel, Nat. Rev. Mater. 2023, 8, 25.Docket No. 30938 / 2024-131

[0012] A. Cafarelli, A. Marino, L. Vannozzi, J. Puigmarti-Luis, S. Pane, G. Ciofani, L. Ricotti, ACS Nano 2021 , 15, 11066.

[0013] T. Kim, H. J. Kim, W. Choi, Y. M. Lee, J. H. Pyo, J. Lee, J. Kim, J. Kim, J.-H. Kim, C. Kim, Nat. Biomed. Eng. 2023, 7, 149.

[0014] P. Pantazis, J. Maloney, D. Wu, S. E. Fraser, Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 14535.

[0015] A. Y. Sonay, K. Kalyviotis, S. Yaganoglu, A. Unsal, M. Konantz, C. Teulon, I.Lieberwirth, S. Sieber, S. Jiang, S. Behzadi, ACS Nano 2021, 15, 4144.

[0016] H.-Y. Liu, H.-Y. Zhang, X.-G. Chen, R.-G. Xiong, J. Am. Chem. Soc. 2020, 142, 15205.

[0017] E. J. Kluender, J. L. Hedrick, K. A. Brown, R. Rao, B. Meckes, J. S. Du, L. M.Moreau, B. Maruyama, C. A. Mirkin, Proc Natl Acad Sci U SA 2019, 116, 40.

[0018] M. Lai, D. Shin, L. Jibril, C. A. Mirkin, J Am Chem Soc 2022, 144, 13823.

[0019] P. T. Smith, C. B. Wahl, J. K. H. Orbeck, C. A. Mirkin, MRS Bull. 2023, 48, 1172.

[0020] P. T. Smith, Z. Ye, J. Pietryga, J. Huang, C. B. Wahl, J. K. Hedlund Orbeck, C. A. Mirkin, J Am Chem Soc 2023, 145, 14031.

[0021] B. C. Steimle, J. L. Fenton, R. E. Schaak, Science 2020, 367, 418.

[0022] S. Du Jingshan, D. Shin, K. Stanev Teodor, C. Musumeci, Z. Xie, Z. Huang, M. Lai, L. Sun, W. Zhou, P. Stern Nathaniel, P. Dravid Vinayak, A. Mirkin Chad, Science Advances, 6, eabc4959.

[0023] F. Huo, Z. Zheng, G. Zheng, L. R. Giam, H. Zhang, C. A. Mirkin, Science 2008, 321, 1658.

[0024] D. J. Eichelsdoerfer, X. Liao, M. D. Cabezas, W. Morris, B. Radha, K. A. Brown, L. R. Giam, A. B. Braunschweig, C. A. Mirkin, Nature Protocols 2013, 8, 2548.

[0025] D. Shin, M. Lai, Y. Shin, J. S. Du, L. Jibril, J. M. Rondinelli, C. A. Mirkin, Adv Mater 2023, 35, e2205923.

Claims

Docket No. 30938 / 2024-131What is claimed is:

1. A method of screening a molecular crystal megalibrary for non-centrosymmetric crystalline structure, comprising:obtaining an optical image of a substrate comprising the molecular crystal megalibrary, wherein the molecular crystal megalibrary comprises a plurality of molecular crystals with a size of about 50 nm to about 5 pm, having a compositional gradient of at least one element of the molecular crystal in at least one x and y direction;scanning the substrate with a multiphoton confocal laser scanning microscope comprising a tunable laser, a focusing objective for focusing the tunable laser on the substrate, and a detector, wherein scanning comprises:dividing the substrate into scanning regions, each scanning region having a size equal to or less than a spot size of a laser when focused on the substrate by the focusing objective,focusing the laser for a scanning time in each scanning region, wherein the molecular crystals having a non-centrosymmetric crystalline structure emit a second harmonic generation signal; anddetecting with the detector the second harmonic generation signal; comparing an image comprising the second harmonic generation signal detected across the substrate to the optical image to identify one or more scanning regions of the optical image in which the second harmonic generation signal was detected; and correlating the one or more regions in which the second harmonic generation signal was detected to compositions of the molecular crystals within the scanning regions, thereby identifying compositions of the molecular crystals having a non-centrosymmetric crystalline structure,wherein the molecular crystal megalibrary comprises at least 1 million molecular crystals per cm2arranged on the substrate; and wherein the second harmonic generation signal has a frequency equal to two times the frequency of the laser.

2. The method of claim 1 , wherein the tunable laser has a wavelength of about 700 nm to about 1300 nm.

3. The method of claim 1 or 2, wherein the molecular crystals comprise, diatomic molecules, polyatomic molecules, or a combination thereof.

4. The method of any one of the preceding claims, wherein the molecular crystals have a size of 2 pm or less.Docket No. 30938 / 2024-1315. The method of any one of the preceding claims, further comprising recording a z coordinate at each scanning region and using the recorded z-coordinate to focus the tunable laser on the scanning region during the scanning time.

6. A method of designing a molecular crystal composition having a target Curie temperature, comprising:obtaining an optical image of a substrate comprising a megalibrary, wherein the megalibrary comprises a plurality of molecular crystals having a compositional gradient of at least one element of the molecular crystal in at least one x and y direction;bringing the substrate to a first measuring temperature less than the target Curie temperature;detecting a second harmonic generation signal from the substrate at the first measuring temperature using a multiphoton confocal laser scanning microscope comprising a tunable laser, a focusing objective for focusing the tunable laser on the substrate, and a detector and generating an image of the detected second harmonic generation signal; repeating one or more times bringing the substrate to a further measuring temperature different from the first measuring temperature and detecting the second harmonic generation signal from the substrate, wherein each further measuring temperature is an increased temperature incrementally between the first temperature and a final measuring temperature, wherein one of the further measuring temperatures is at the target Curie temperature;comparing the images of the detected second harmonic generation signal at the further measuring temperatures and the image of the detected second harmonic generation signal at the first measuring temperature and identifying one or more regions of the images in which the second harmonic generation signal is detected at each of the further measuring temperatures below the Curie temperature and is not detected at the further measuring temperatures at or above the target Curie temperature,correlating the identified one or more regions to the optical image, thereby identifying compositions of the molecular crystals having a non-centrosymmetric crystalline structure at the first measuring temperature and the target Curie temperature;wherein detecting the second harmonic generation signal from the substrate at the first and further measuring temperatures comprises:dividing the substrate into scanning regions, each scanning region having a size equal to or less than a spot size of the tunable laser when focused on the substrate by the focusing objective,focusing the tunable laser for a scanning time in each scanningDocket No. 30938 / 2024-131region, wherein molecular crystals having a non-centrosymmetric crystalline structure emit a second harmonic generation signal; anddetecting with the detector the second harmonic generation signal, andwherein the megalibrary comprises at least 1 million crystals per cm2arranged on the substrate; wherein the second harmonic generation signal has a frequency equal to two times the frequency of the tunable laser.

7. The method of claim 6, wherein bringing the substrate to the further measuring temperature comprises heating the substrate in an increment in a range of about 0.5 to about 10 degree C.

8. The method of claim 6 or 7, wherein the final measuring temperature is at the target Curie temperature.

9. The method of any one of claims 6 to 8, wherein the final measuring temperature is higher than the target Curie temperature.

10. A method of identifying a Curie temperature for a molecular crystal composition, comprising:providing a substrate comprising a megalibrary, wherein the megalibrary comprises a plurality of molecular crystals having the composition; anddetecting a second harmonic generation signal from the substrate at a plurality of measuring temperatures using a multiphoton confocal laser scanning microscope comprising a tunable laser, a focusing objective for focusing the tunable laser on the substrate, and a detector, wherein the substrate is divided into scanning regions, each having a size equal to or less than a spot size of a laser when focused on the substrate by the focusing objective and detecting the second harmonic generation signal at each measuring temperature comprises:brining the substrate to the measuring temperature,focusing the laser for a scanning time in each region, wherein molecular crystals having a non-centrosymmetric crystalline structure emit a second harmonic generation signal, anddetecting with the detector the second harmonic generation signal; wherein the first measuring temperature is a temperature at which the molecular crystal composition generates a second harmonic generation signal, and a lowest temperature of the plurality of measuring temperatures at which a second harmonic generation signal is not detected from the substrate is a Curie temperature of theDocket No. 30938 / 2024-131composition, wherein the second harmonic generation signal has a frequency equal to two times the frequency of the light beam.

11. The method of claim 10, further comprising displaying the detected second harmonic generation signal at each measuring temperature as an image and wherein the images at different temperatures are compared to each other to identify the Curie temperature.

12. The method of claim 10 or 11 , further comprising displaying the detected second harmonic generation signal at each measuring temperature as an intensity plot, wherein each measuring temperature has an intensity peak and wherein the intensity peak decreases as the measuring temperature approaches the Curie temperature of the composition.

13. A molecular crystalline compound having a formula TMCMZTMA(i-Z) Cd C , wherein z has a value in a range of about 0.4 to about 1.

14. A molecular crystalline compound having a formula TMCM CdzPb(i-Z) C , wherein z has a value in a range of about 0.5 to about 1.

15. The molecular crystalline compound of claim 13 or 14, wherein the compound has a non-centrosymmetric structure.

16. The molecular crystalline compound of claim 13 or 14, having a crystalline structure wherein the crystalline structure has a point group selected from the group consisting of: 1, 2, m, 222, mm2, 4, ~4, 422, 4mm, "42m, 3, 32, 3m, 6, "6, 622, 6mm, "6m2, 23, 432 or"43m.

Images