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Edit: As Kim Scheinberg pointed out in the comments, "set" may actually be on the way out. According to the editors of the next edition of the OED (in progress), "run" has finally overtaken it, with a gobsmacking 645 definitions (‘Run,’ a Verb for Our Frantic Times). Over half a thousand meanings, once again for a slim three-letter word. Regardless, I believe "set" still takes the prize away in the current edition, and as the next edition won't be ready until 2037, the answer below should stand as officially "correct" for at least a while longer. Anyway, here's the original answer:You won't find a better candidate than the word "set." But it's so simple, you might think. How many meanings could such a teensy word actually have?That's right, a whopping four hundred sixty-four. In the Oxford English Dictionary, the ultimate record of the English language, "set" handily takes away the gold medal for the most definitions. The next closest is "run," at a comparatively paltry 396.Some things to keep in mind about this: unlike, say, "Progress" and "proGress," "set" doesn't offer us the ability to distinguish it's meanings through different pronunciations or by stressing a different syllable. This shows how crucially important context is in deciphering what others mean: every time someone says "set," you've got to figure out, without any auditory clues, which of the nearly 500 possible meanings they meant. And you've got to do it in a split-second so you can keep up with the rest of what they're going on about. But it also shows how good we are at this: when's the last time you had trouble understanding what somebody really meant when they said "set"?Anyway, I'm sure this is why any of you who are are still reading: what are these definitions? I can't post the Oxford English Dictionary's list itself, since you have to pay for it, but I will post the next best thing, which is the set of entries available at TheFreeDictionary.com. (Keep in mind that some dictionaries are less detailed than others, and few are as detailed as the OED, so you might not see all 464 here. Also, posting all of them would make this post unbearably huge.) These entries on their site all come from the fourth edition of The American Heritage Dictionary of the English Language, though there are entries from other dictionaries at the site (http://www.thefreedictionary.com/set). So, without further ado, here are 146 of the 464 meanings of "set" available from the above source. How many do you recognize?set 1v. set, set·ting, setsv.tr.1. To put in a specified position; place: set a book on a table.2. To put into a specified state: set the prisoner at liberty.3.a. To put into a stable position: set the fence post into a bed of concrete.b. To fix firmly or in an immobile manner:He set his jaw and concentrated on flying the plane through the storm.4. To restore to a proper and normal state when dislocated or broken: set a broken arm.5.a. To adjust for proper functioning.b. To adjust (a saw) by deflecting the teeth.c. Nautical To spread open to the wind:set the sails.6. To adjust according to a standard.7. To adjust (an instrument or device) to a specific point or calibration: set an alarm clock.8. To arrange properly for use: set a place for a dinner guest; set a table.9. To apply equipment, such as curlers and clips, to (hair) in order to style.10. Printinga. To arrange (type) into words and sentences preparatory to printing; compose.b. To transpose into type.11. Musica. To compose (music) to fit a given text.b. To write (words) to fit a given melodic line.12. To arrange scenery on (a theater stage).13. To prescribe the unfolding of (a drama or narrative, for instance) in a specific place: a play that is set in Venice.14. To prescribe or establish: set a precedent.15. To prescribe as a time for: set June 6 as the day of the invasion.16. To detail or assign (someone) to a particular duty, service, or station: set the child to cleaning the closets; set guards around the perimeter.17. To incite to hostile action: a war that set families against one another.18.a. To establish as the highest level of performance: set a world aviation record.b. To establish as a model: A parent must set a good example for the children.19.a. To put in a mounting; mount: set an emerald in a pendant.b. To apply jewels to; stud: a tiara that was set with diamonds.20. To cause to sit.21.a. To put (a hen) on eggs for the purpose of hatching them.b. To put (eggs) beneath a hen or in an incubator.22. Sports To position (oneself) in such a way as to be ready to start running a race.23. Sports To pass (a volleyball), usually with the fingertips, in an arc close to the net so that a teammate can drive it over the net.24.a. To value or regard something at the rate of: She sets a great deal by good nutrition.b. To fix at a given amount: The judge set bail for the defendant at $50,000.c. To make as an estimate of worth: We set a high value on human life.25. To point to the location of (game) by holding a fixed attitude. Used of a hunting dog.26. Botany To produce, as after pollination: set seed.27.a. To prepare (a trap) for catching prey.b. To fix (a hook) firmly into a fish's jaw.v.intr.1. To disappear below the horizon: The sun set at seven that evening.2. To diminish or decline; wane.3. To sit on eggs. Used of fowl.4.a. To become fixed; harden. See Synonyms at coagulate.b. To become permanent. Used of dye.5. To become whole; knit. Used of a broken bone.6. Botany To mature or develop, as after pollination.7. Nonstandard To sit: "If Emmett drives, I could set up front" (Bobbie Ann Mason).8. To position oneself preparatory to an action, such as running a race.adj.1. Fixed or established by agreement: a set time for the launching.2. Established by convention: followed set procedures for filing a grievance.3. Established deliberately; intentional: Our set purpose is to win the conflict.4. Fixed and rigid: "His bearded face already has a set, hollow look" (Conor Cruise O'Brien).5. Unwilling or very reluctant to change: He is set in his ways.6.a. Intent and determined: "He is dead set against rushing abroad to build a plant"(Fortune).b. Ready: We are set to leave early tomorrow morning.n.1.a. The act or process of setting.b. The condition resulting from setting.2. The manner in which something is positioned:the set of her cap.3. A permanent firming or hardening of a substance, as by cooling.4. The deflection of the teeth of a saw.5.a. The carriage or bearing of a part of the body.b. A particular psychological state, usually that of anticipation or preparedness: "The mental set of an audience is crucial to his performance" (Psychology Today).6. A descent below the horizon.7. The direction or course of wind or water.8. A seedling, slip, or cutting that is ready for planting.9. The act of arranging hair by waving and curling it.10. Sports The act of setting a volleyball for a teammate.Phrasal Verbs:set aboutTo begin or start: set about solving the problem.set apart1. To reserve for a specific use.2. To make noticeable: character traits that set her apart.set aside1. To separate and reserve for a special purpose.2. To discard or reject.3. To declare invalid; annul or overrule: The court has set aside the conviction.set atTo attack or assail: The dogs set at the fox.set back1. To slow down the progress of; hinder.2. Informal To cost: That coat set me back $1,000.set byTo reserve for future use: It is wise to set food and money by in case of a future emergency.set down1. To cause to sit; seat: Set the baby down here.2. To put in writing; record: We set down the facts.3.a. To regard; consider: Just set him down as a sneak.b. To assign to a cause; attribute: Let's set the error down to inexperience.4. To land (an aircraft): The pilot set the plane down hard.5. Baseball To put out (a batter); retire. Used of a pitcher.set forth1. To present for consideration; propose: set forth a sound plan.2. To express in words: She has set forth her ideas.set forwardTo begin a journey.set in1. To insert: set in the sleeve of a gown.2. To begin to happen or be apparent: "Evening was setting in as I took the road over Mountain Top" (Charles Siebert).3. To move toward the shore. Used of wind or water.set off1.a. To give rise to; cause to occur: set off a chemical reaction.b. To cause to explode: set off a bomb.c. To make suddenly or demonstrably angry: The clerk's indifference finally set me off.2. To indicate as being different; distinguish:features setting him off from the crowd.3. To direct attention to by contrast; accentuate:set off a passage with italics.4. To counterbalance, counteract, or compensate for: Our dismay at her leaving was set off by our knowing that she was happy.5. To start on a journey: set off for Europe.set out1. To begin an earnest attempt; undertake: He set out to understand why the plan had failed.2. To lay out systematically or graphically: set out a terrace.3. To display for exhibition or sale.4. To plant: set out seedlings.5. To start a journey: She set out at dawn for town.set to1. To begin working energetically; start in.2. To begin fighting.set up1. To place in an upright position.2.a. To elevate; raise.b. To raise in authority or power; invest with power: They set the general up as a dictator.c. To put (oneself) forward as; claim to be:He has set himself up as an authority on the English language.d. To assemble and erect: set up a new machine.3. To establish; found: set up a charity.4. To cause: They set up howls of protest over new taxes.5. To establish in business by providing capital, equipment, or other backing.6. Informala. To treat (someone) to drinks.b. To pay for (drinks).7. Informal To stimulate or exhilarate: a victory that really set the team up.8. To lay plans for: set up a kidnapping.9. Informal To put (someone else) into a compromising situation by deceit or trickery:Swindlers have set me up.10. Sports To make a pass to (a teammate), creating a scoring opportunity.set uponTo attack violently: Guards set dogs upon the escaping prisoners.Idioms:set fire toTo cause to ignite and burn.set foot inTo enter.set foot onTo step on.set in motionTo give impetus to: The indictment set the judicial process in motion.set (one's) heart onTo be determined to do something.set (one's) sights onTo have as a goal: She set her sights on medical school.set on fire1. To cause to ignite and burn.2. To cause to become excited: The music set the audience on fire.set sail NauticalTo begin a voyage on water.set (someone) straightTo correct (someone) by providing full and accurate information.set store byTo regard as valuable or worthwhile.set the pace1. To go at a speed that other competitors attempt to match or surpass.2. To behave or perform in a way that others try to emulate.set the stage forTo provide the underlying basis for: saber rattling that set the stage for war.set up housekeepingTo establish a household.set up shopTo establish one's business operations.set 2n.1. A group of things of the same kind that belong together and are so used: a chess set.2. A group of persons sharing a common interest:the high-school set.3. A group of books or periodicals published as a unit.4.a. A number of couples required for participation in a square dance.b. The movements constituting a square dance.5.a. The scenery constructed for a theatrical performance.b. The entire enclosure in which a movie is filmed; the sound stage.6. Musica. A session of music, typically dance music, played before an intermission.b. The music so played.7. The collective receiving apparatus assembled to operate a radio or television.8. Mathematics A collection of distinct elements having specific common properties: a set of positive integers.9. Sportsa. A group of games constituting one division or unit of a match, as in tennis.b. An offensive formation in football or basketball.

Photonic crystals: emerging biosensors and their promise for point-of-care applicationsHakan Inan, Muhammet Poyraz, [...], and Utkan DemirciAdditional article informationAbstractBiosensors are extensively employed for diagnosing a broad array of diseases and disorders in clinical settings worldwide. The implementation of biosensors at the point-of-care (POC), such as at primary clinics or the bedside, faces impediments because they may require highly trained personnel, have long assay times, large sizes, and high instrumental cost. Thus, there exists a need to develop inexpensive, reliable, user-friendly, and compact biosensing systems at the POC. Biosensors incorporated with photonic crystal (PC) structures hold promise to address many of the aforementioned challenges facing the development of new POC diagnostics. Currently, PC-based biosensors have been employed for detecting a variety of biotargets, such as cells, pathogens, proteins, antibodies, and nucleic acids, with high efficiency and selectivity. In this review, we provide a broad overview of PCs by explaining their structures, fabrication techniques, and sensing principles. Furthermore, we discuss recent applications of PC-based biosensors incorporated with emerging technologies, including telemedicine, flexible and wearable sensing, smart materials and metamaterials. Finally, we discuss current challenges associated with existing biosensors, and provide an outlook for PC-based biosensors and their promise at the POC.1. IntroductionBiosensing is an emerging analytical field for the detection of biochemical interactions leveraging electrical, optical, calorimetric, and electrochemical transducing systems.1,2These transduction mechanisms are employed to translate changes and variations within the biological domain into a readable and quantifiable signal (e.g., association, dissociation, and oxidation).3Biosensors are most notably employed for detecting various biological targets, such as cells,4bacteria,5,6viruses,7proteins,8hormones,9enzymes,10and nucleic acids,11to facilitate the diagnosis and prognosis of diseases. Currently, state of the art clinical laboratories require trained personnel to perform sample collection, testing, and analysis using sophisticated biosensing devices in centralized clinical settings (Fig. 1). Staffing the necessary personnel to ensure accurate and reliable readings can be costly, and results are subject to operator error.12,13Although certain automated instrumentation has been used to simultaneously process multiple patient samples at large volumes (e.g., hematology analyzers), technicians are still needed for device oversight and maintenance.14,15Centralized laboratories also perform immunoassays and nucleic amplification strategies, but these methods are time consuming, labor intensive, and expensive. As an example, enzyme-linked immunosorbent assay (ELISA) requires several experimental steps, including antibody immobilization, target binding, labeling, substrate incubation, signal production, and multiple washing steps.16,17Fig. 1Current challenges of biosensing tests for the POC applications. Biosensors face critical impediments at the POC due to large sample volume, transfer of samples to a central site, and being bulky and expensive. These challenges are most obvious at remote ...Recently, substantial research efforts have been devoted to the development of in vitrodiagnostic tests including point-of-care (POC) devices with the market volume estimated to reach US$ 75.1 billion by 2020.18One of the main drivers for these POC technologies is the detection of diseases in resource-limited countries.19–25For example, commercial POC kits have been recently developed to detect human immunodeficiency virus (HIV) and tuberculosis in such settings.26However, there are significant logistical, technical, and social barriers that need to be overcome when performing testing at these sites, and many of these technologies still require the recruitment and training of personnel (Fig. 1).14,27–29,30Thus, there exists a need to develop affordable, sensitive, rapid, portable, label-free, and user-friendly POC diagnostic tools.31–33Incorporation of microfluidics and nanotechnology into biosensing platforms holds great promise to address the aforementioned challenges. Sensitive technologies, such as localized and surface plasmon resonance, electrical sensors, interferometric biosensors, and photonic crystal (PC)-based bio-sensors, have been employed as diagnostic devices (Table 1).34–40PC-based biosensors hold many advantages over other existing competing biosensing technologies, including cost-effective fabrication and short assay time (Table 2). PC structures have been used to detect a wide array of biotargets in biological sample matrices, such as blood, urine, sweat, and tears,41–43and can be fabricated using various inexpensive fabrication methods, such as colloidal self-assembly, hydrogels, and mold-based replica imprinting.44–46Table 1General overview of PC-based biosensorsTable 2Comparison of PC-based biosensors with selected competing technologiesIn this review, recent incorporation of PC structures within emerging label-free biosensing platforms is discussed, including their applications for detecting proteins, nucleic acids, allergens, pathogens, and cancer biomarkers.47–50We will also provide a broad overview of PC structures and PC-based biosensors and their potential utilization as POC diagnostic tools. We describe various aspects of PC-based biosensors, including (i) PC structures and fabrication techniques, (ii) principles of PC-based biosensing, (iii) emerging technologies incorporating PC-based biosensors for potential POC applications, (iv) multi-target detection capability for PC-based biosensors, (v) surface chemistry approaches, (vi) current challenges and limitations for biosensors at the POC, and (vii) future outlook for PC-based biosensors at POC diagnostics.2. Photonic crystal structures and fabrication techniquesPC structures consist of spatially arranged periodic dielectric materials that uniquely interact with light, providing high efficiency reflection at specific wavelengths. There are many examples of PC-type periodically nanostructured surfaces observed in nature.51For instance, the bright iridescent color of the Morpho rhetenor butterfly,52peacock,53Eupholus magnificus insect,54sea mouse55and opals56are all associated with the geometrical arrangement on their surface, where broadband light illuminates and reflects through PC structures (Fig. 2).52In practice, PC structures can be fabricated in one-dimensional (1-D), two-dimensional (2-D) or three-dimensional (3-D) orientations incorporating microcavities,57waveguides,58slabs,59multi-layered thin films,60and porous geometries61(Fig. 3). A diverse range of materials, such as silicon (Si),62glass,63polymers,64colloids,65–68and silk,69–71are used in the fabrication of PC structures (Table 1).Fig. 2PC structures commonly found in the nature. Bright iridescent color of these objects is due to the presence of geometrical periodic elements in their structures. Shown are four types of PC structures: 1. (a and b): 1-D (Morpho rhetenor butterfly), 2. ...Fig. 3Types of photonic crystals. (a) 1-D slab is one of the most exploited PC structures for biosensing applications. Refractive index alternates in one dimension only (in x, or in yaxis) by forming air gaps in between substrate structures.227It also possess ...PC structures are fabricated using various methods, including self-assembly and lithography techniques. For instance, colloids composed of hydrogel polymers,72silica,73or polystyrene74are transferred from solution and self-assembled (viasedimentation, spin coating, or vertical deposition44,75) onto a surface to create PC structures that reflect iridescent color.75–77In addition, hydrogels are utilized in combination with colloidal particles in the fabrication of PC structures. While these self-assembly methods are inexpensive, precisely controlling the dimensions and geometry of the underlying PC structure is difficult. Top-down approaches, including electron beam lithography (e-beam), nanoimprint lithography (NIL), electrochemical etching, and thin film deposition techniques,78,79are alternatives to bottom-up self-assembly methods. Briefly, in the e-beam process, an electron beam is used to write a desired pattern onto a substrate (often silicon), which is previously coated with an electron-sensitive resist. The resist is then developed, and the electron-beam pattern is transferred to the substrate via etching. Performing this method requires e-beam lithography devices, which are large, expensive and require skilled operators. NIL is a rapid, simple, and scalable pattern transfer technique alternative to e-beam lithography.80In NIL, a pattern is initially produced using deep UV/e-beam lithography on a master mold, which can be easily transferred to daughter replicas. The NIL method has been used to mass-produce PC structures rapidly and reliably; however, only a finite number of replicas can be generated from a single mold due to wear.79Electrochemical etching can be used to fabricate porous Si structures that produce a photonic band gap due to formed periodic trenches. Electrochemical etching of Si is inexpensive and can be performed in research labs. Although trenches and channels provide a higher surface area for chemical interactions, large biomolecules may cause aggregation and blocking of the channels (e.g., cells) when using clinical samples.Overall, a wide range of materials and fabrication methods is available for the development of PC structures. Using PC structures for POC applications is highly feasible due to the availability of inexpensive fabrication materials such as hydro-gels and colloidal particles and the scalable production method using NIL. The theoretical background behind the PC phenomenon and how these PC structures are used as biosensors are discussed in the following section.3. Principles of PC-based biosensingA periodic arrangement of dielectric materials creates a photonic band gap when a range of electromagnetic waves cannot propagate due to the destructive interference of incident light with reflections at dielectric boundaries.81PC structures can be produced from a variety of geometries, including Bragg reflectors, slabs, opals, microcavities, and colloids. An optical phenomenon describing most of these structures can be deduced from understanding a simple Bragg structure. A typical Bragg reflector consists of alternating high and low refractive index dielectric thin film layers (Fig. 4a). The optical thicknesses of these layers are designed to be one quarter of the wavelength of incident light (λ) (eqn (1)). Multiple reflections from consecutive layers provide constructive interference and result in total reflection (Fig. 4b). Light at this reflected wavelength resides in a photonic band gap region (Fig. 4c), and cannot propagate at normal incidence.82Fig. 4The design and optical response of simple PCs. (a) A Bragg reflector consisting of alternating low and high refractive index of dielectric layers. At specific wavelengths, reflections from consecutive layers constructively interfere with each other and ...(1)Another common PC structure is comprised of periodically modulated thin films, which are known as 1-D slabs. 1D-PC structures are commonly fabricated from a high refractive index coating layer over a periodically arranged low refractive index grating layer (Fig. 4d). In these PC gratings, only the zeroth order mode is allowed, while higher order modes are restricted at normal incidence, provided that the period of the grating (Λ) is smaller than the wavelength of the incident light (Λ < λ). Gratings of this type are also called subwavelength gratings, and exhibit efficient optical resonances.83Subwavelength PC gratings can be designed to reflect a narrow band of wavelengths and produce a sharp peak in the reflection spectrum (Fig. 4e).84,85Resonance occurs when a diffracted mode from the grating couples to a leaky waveguide mode. Radiation from the leaky mode constructively interferes with the reflected wave and destructively interferes with the transmitted wave, resulting in a resonant reflection.83The resonance wavelength peak is determined by the period (Λ) of PC gratings and the effective refractive index (neff) under resonance conditions (eqn (2)).86λresonance= neffΛ(2)This resonance behavior of PC gratings is highly sensitive to the localized changes in dielectric permittivity on the crystal surface, which makes it suitable for sensing applications. In this regard, PC structures are widely utilized to develop sensing platforms for multiple applications of chemical sensing, environmental sensing, and more specifically, biosensing.87–90Briefly, a biochemical interaction (e.g., binding) on the PC surface causes a change in the effective refractive index, which results in a shift of the resonance wavelength peak, which is proportional to the concentration of the biotarget (Fig. 5). PC structures have gained significant attention as sensitive transducers and have been incorporated into biosensors that capture, detect, and quantify various biological molecules, such as pathogens,7,47,91–96DNA,97–101proteins, enzymes,102,103glucose,42,104–106cells,107,108toxins,109and allergens.110Fig. 5Overall mechanism of biosensing using photonic crystals. (a) An example of the 1-D PC slab surface. (b) Corresponding resonance peak wavelength for this PC slab. (c) Functionalization of the slab surface and biological binding event via antigen–antibody ...4. Emerging technologies incorporating PC-based biosensors for potential POC applicationsRecent advances in microfluidics, telemedicine, flexible materials, and wearable sensing technologies hold promise to provide compact and portable platforms in biosensing applications at POC for the rapid, reliable, accurate, on-site, and label-free detection of biotargets.111–1184.1 MicrofluidicsMicrofluidics technology offers considerable benefits to bio-sensing systems, particularly the POC devices. These advantages include (i) inexpensive fabrication materials (e.g., glass, paper and polymers), (ii) ability to control low sample volume, (iii) ease of integration with optical platforms, and (iv) flexibility in producing multiple channels to allow multiplexed testing platforms.119–121PCs-integrated with microfluidic technologies are emerging as powerful biosensing diagnostic tools with the integration of these features.50,122For instance, integration of 1-D PC slabs within a microfluidic channel network at the bottom of a 96-well plate was used to detect immunoglobulin gamma (IgG).46This microfluidic-integrated platform enabled the concurrent multiplex detection of molecules using only 20 μL of the sample (Fig. 6). In another study using a colloidal polystyrene-based PC structure integrated with microfluidics, IgG molecules were captured and detected down to mg mL−1levels.123PC structures have also been incorporated with polymer microfluidic channels to detect proteins; for example, a slotted PC cavity fabricated from Si was shown to detect 15 nM of avidin protein.124,125Fig. 6PC biosensors integrated with microfluidic platforms for POC applications. (a) Multi-well plate integrated with a network of microfluidic channels with PC-based biosensors at the bottom. Reproduced from ref. 46 with permission from The Royal Society of ...4.2 TelemedicineSmartphones have been increasingly utilized in medical diagnostics and healthcare applications, such as cell counting from whole blood, immunoassay testing, and imaging.111,126,127Smartphones will likely play an important role in the development of new biosensing platforms due to their wide availability, portability, compactness, capacity for data processing, ease of integration with microfluidic devices, and high-resolution optical components.111,128Recently, camera and optical systems in cell-phones have been integrated with microfluidic, microscopy, and photonic crystal technologies for the spectral analyses of bio-sensing applications.126,129–134For instance, a 1-D PC slab was integrated with a smartphone to measure IgG concentration. The phone camera was used as a spectrometer to measure the transmission spectrum from the PC structures.135Although the system produced a reliable dose–response curve, adsorption of biomolecules could only be measured under dry conditions. Thus, further study with aqueous samples is required before this platform could be used to directly analyze clinical samples at the POC. In another study, a 1-D PC slab was integrated with a complementary metal–oxide–semiconductor (CMOS)-based smartphone camera to detect anti-recombinant human protein CD40 (Cluster of Differentiation-40), streptavidin, and anti-EGF antibody (Fig. 7).136Fig. 7PC structure integrated with a smartphone for biosensing applications at the POC. (a) Drawing representing a general scheme of a PC incorporated smartphone. The CCD camera of the phone was utilized as an optical sensing element. (b) Actual image of the ...Smartphone-integrated platforms hold promise to address portability related issues at the POC, though their direct use in clinical applications is challenging because complex specimens, such as blood and tissue, need to be preprocessed before being brought into contact with the device.4.3 Wearable and flexible sensorsWearable sensors and flexible materials have recently gained attention for continuous and real-time monitoring of the physiological parameters and general health status of individuals.137–142For instance, they have been employed to measure the heart rate, skin temperature, blood oxygen levels, and more recently glucose sensing from sweat.143–145Wearable sensors are currently worn as wristbands, skin patches, and fabric patches. From a fabrication perspective, various nanotechnology-based techniques and materials are used for the production of these flexible and wearable sensors. In a recent study, a PC structure was designed with 2-D holes (with a diameter of ~100 nm) to evaluate strain changes.146This flexible sensor could be bent without losing its optical properties (Fig. 8a and b), and provided a sensitivity that was independent of deformation. In another study, colloidal polystyrene spheres were deposited on a flexible polyimide film.147A strain applied over this flexible film resulted in a blue shift in the reflection maxima (Fig. 8c and d).Fig. 8Flexible and wearable PCs in sensing applications. (a) Picture of the Si membrane integrated with a photonic crystal. (b) 2-D holes with a waveguide to couple light into a flexible photonic crystal structure. Reproduced from ref. 146, copyright (2014) ...3-D PC structures have also been incorporated into wearable sensors. For example, 3-D PC structures were investigated under pressure and may conceptually be used for detecting the severity of blast exposure to evaluate traumatic brain injury of soldiers in the battlefield.148,149In this study, 3-D voids were fabricated in an SU-8 resist to create 3-D PC structures that exhibited a color in the visible spectrum. These structures were exposed to varying high pressures (410 to 1090 kPa) to measure blast strength (Fig. 8e), and it was determined that large external forces could be detected by visual inspection (Fig. 8f–h). The PC structure that was exposed to high external forces underwent structural deformation, resulting in a color change. This change was used to estimate the degree of pressure on the PC structure. While this work is promising, using these detectors on soldiers’ uniforms is conceptual and their implementation in this field has not yet been evaluated.4.4 Smart materialsSmart materials are an emerging class of responsive substances that can modify their physical or chemical properties, mostly reversibly, against external stimuli such as pH, temperature, electrical field, and light.150,151Smart materials, such as hydrogels, polyionic liquids, graphene, and carbon nanotubes (CNTs), have been used for various applications, including biosensing. In particular, their incorporation into PC structures holds promise for rapid, sensitive, and reliable biosensing. Hydrogel materials are 3-D nanostructured polymers consisting mostly of water. Hydrogels may be responsive to external stimuli, such as temperature, pH, or bio-stimuli such as antigen–antibody interactions.45,72,152–155For instance, PC structures comprised of hydrogel materials can be used as biosensors for the detection of DNA, proteins, antibodies and enzymes by monitoring the changes in lattice spacing or refractive indices.41,43,156–159In this respect, hydrogel-based PC structures provide either quantitative spectral results or qualitative naked-eye detection of biotarget concentrations.41Hydrogel-based PC structures hold great promise for POC applications owing to their cost-effective fabrication and simple optical detection systems. In a recent study, a hydrogel-based nanoporous PC structure was employed for label-free detection of rotavirus with concentrations ranging from 6.35 μg mL−1to 1.27 mg mL−1(Fig. 9a and b).160Polyionic liquids (PILs) are a class of polymeric materials containing repeating ionic monomeric units, which have recently been demonstrated for sensing applications.161,162In one such study, PIL was used to fabricate a 3-D macroporous PC structure, that exhibited Bragg reflection in the visible wavelength range, to detect a variety of ions.163Fig. 9Smart material- and metamaterial-based PCs for sensing. (a) Hydrogel-based PCs for the detection of rotavirus. (b) SEM image of the hydrogel structure. (a and b are reproduced from ref. 160 with permission from The Royal Society of Chemistry) (c) 3-D ...Hydrogels can also be used in combination with other materials including graphene or carbon nanotubes (CNTs) to produce PC structures. In one such study, graphene oxide was deposited on a silicon wafer and embedded into a hydrogel matrix to detect beta-glucan.164Graphene based-PC structures have also been investigated for enhanced sensitivity biosensing.165In addition, CNTs were incorporated into PC structures that provided a photonic band gap in the visible light spectrum.166Recently, CNT-based PC structures were investigated for optical applications.167–169Smart materials have been studied extensively and have the potential to be utilized as biosensors due to the unique properties of each material. However, they require further validation using clinical matrices.4.5 MetamaterialsRecently, PC structures based on metamaterials have been investigated for various applications, including imaging and biosensing.169–172For instance, a PC metamaterial with a 3-D woodpile geometry was proposed to excite plasmons with high spectral sensitivity.170The proposed structure was a silver-coated woodpile crystal providing a high surface-to-volume ratio with a sensitivity more than 2600 nm per refractive index unit (RIU) (Fig. 9c and d). In another study, a hyperbolic metamaterial biosensor consisting of 16 alternating layers of thin Al2O3(aluminum oxide) and gold layers was demonstrated to detect biotin (Fig. 9e) with very high sensitivity up to 30 000 nm per RIU.171This 1-D multilayer structure supported guided modes ranging from visible to near infrared, enabled optical biosensing at different spectral regions with ultra-high spectral sensitivity, and detected 10 pM biotin in phosphate buffered saline (Fig. 9f). Light coupling was achieved with a 2-D gold diffraction grating on top of the multilayer films, eliminating the need for additional optical elements (e.g., prism). Although metamaterial-based biosensors enable label-free detection with high sensitivity, they require multiple fabrication steps and may not be compatible with clinically relevant matrices (i.e., whole blood, urine, and saliva).Overall, the integration of PC structures with emerging technologies is promising for biosensing applications at POC owing to compact, flexible, and easy-to-use platforms. In particular, PC-based biosensors composed of smart materials may create a new class of flexible and wearable POC sensors with high sensitivity.5. Multi-target detection capability for PC-based biosensorsPC-based biosensors have been employed to detect multiple biological targets, such as pathogens, proteins, nucleic acids, and glucose, for the diagnosis of a broad range of diseases, including diabetes and cancer. Here, we provide a broad perspective of using PC structures to quantify various molecular interactions ranging from biotin–streptavidin to cancer biomarkers.1735.1 Protein detectionPC structures have been used to capture and detect numerous proteins, such as protein A, Immunoglobulin Gamma (IgG), bovine serum albumin (BSA), and Protein G.157,174,175Streptavidin is often used in conjugation with biotin in experiments to validate the sensitivity and detection limit of new PC geometries due to the extraordinary affinity of streptavidin for biotin.123,176,177PC structures have been employed to investigate the substrate specificity and catalytic activity of certain enzymes, such as acetyl cholinesterase, pepsin and other proteases.103,178In one study, a porous Si-based PC structure was developed to evaluate proteolytic activities of pepsin and subtilisin proteases down to 7 pmol and 0.37 pM, respectively. When coupled with a fluorescence assay, a PC surface can significantly amplify the fluorophore intensity, increase the signal-to-noise ratio and reduce the detection limits. For example, a PC structure was coupled with fluorescence-labeled secondary antibody to detect TNF-α concentrations at pg mL−1levels.185The ability of an assay to detect disease targets at low concentrations at an early stage is very important. In this research, imaging of the PC spots was performed for the multiplex detection of different proteins.Colloidal PC structures have also been widely employed for protein detection. For instance, arranged colloidal nanoparticles embedded inside a hydrogel were used to visually monitor a reflectance shift in response to protein concentration.157In this study, silica nanoparticles were embedded within a poly(ethylene glycol)-diacrylate hydrogel to generate a PC structure. This system was able to observe IgG proteins bound to protein A on the surfaces of the embedded nanoparticles. A color change from orange to green was observed after exposure to 10 mg mL−1IgG, and the detection limit in the color shift was at the concentration of 0.5 mg mL−1IgG (Fig. 10). Since this procedure uses a self-assembly deposition method and does not require advanced manufacturing technology, it is cost-effective; however, the concentrations necessary to observe a visual change are high, and thus, may not be compatible with sensitive detection applications.Fig. 10PC biosensor for capturing and quantification of protein molecules. (a) Colloid PC structure was used to capture IgG proteins. (b) IgG bound to the colloid PC surface and changed the reflected color. (c) Image of the PC surface. A color shift was observed ...By coupling with fluorescence-labeled secondary antibodies, PC-based biosensors have also been utilized to capture allergen-specific immunoglobulin (IgE) antibodies.110,179,180PC structures can enhance fluorescence signals when the optical resonance of the PC surface overlaps with either the excitation or emission spectra of a fluorophore. This enhanced excitation and emission yielded ~7500-fold increase in fluorescence signals.181In a recent study, a PC-enhanced fluorescence (PCEF) microarray platform was used to detect low concentrations of IgE in human sera with a limit of detection of 0.02 kU L−1, which was comparable to current blood-based IgE detection methods.110However, current PC-based allergen platforms rely on fluorescence detection, which limits their use at the POC due to the requirements for labeling, additional instrumentation, and multiple assay preparation steps.5.2 Nucleic acid detectionBiosensing of DNA, RNA, and DNA–protein interactions using PC-based platforms has been studied for various applications, including the determination of infectious agents, identification of genetic disorders,182–185and monitoring of DNA–protein interactions.97,173,186For instance, DNA and protein interactions were evaluated using a 1-D PC slab structure with a TiO2layer over a low index material, and DNA was detected down to nanomolar concentrations.173In this study, a panel of 1000 compounds were screened on a microplate-integrated PC-based biosensing platform (Fig. 11a–c). This platform uses multiple fibers, a motorized stage, and a coupled readout system (SRU Biosystems Bind Reader) capable of recording simultaneous readings from 384-wells. This platform has significant potential for drug-screening studies at the POC in resource-constrained settings since it incorporates a disposable and inexpensive 384-well microplate. The platform can further be utilized for the detection of RNA–protein and protein–protein interactions, and may shed light on gene expression at the cellular and molecular levels.187In addition to 1-D PC slab structures, colloid PCs have also been utilized for nucleic acid detection. In this study, self-assembled polystyrene beads were utilized to fabricate a colloidal PC structure that could detect hybridized DNA down to 13.5 fM.188In another study, a planar waveguide was employed for the detection of single-stranded DNA at a concentration of 19.8 nM.98The use of PC structures is a promising alternative to the conventional polymerase chain reaction (PCR) techniques for nucleic acid detection due to their low cost, ease-of-use, rapid response, and high detection capacities.Fig. 11Monitoring DNA–protein interaction using a PC biosensor. (a) Image of a 384-well plate integrated with a PC platform for drug screening. (b) Drug screening for protein–DNA binding inhibition. An outstanding molecule was recorded using ...5.3 Applications in cancerBiosensors are widely employed in the detection of biomarkers for diagnosis and prognosis of cancer. Currently, various bio-markers, such as epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), tumor necrosis factor-α (TNF-α), and calreticulin (CRT), are under clinical study for diagnosis of cancer.189–191Detecting these biomarkers at an early stage of malignancy can contribute to better treatment outcomes and significantly increase the quality of life for cancer patients.Recently, PC-based biosensors have been employed in diagnosis and early detection of cancer.189,192,193In one study, a waveguide integrated with a cavity was employed for the detection of CEA protein for the diagnosis of colon cancer (Fig. 11d–f).192This platform provided a detection limit for CEA protein down to the 0.1 pg mL−1level. In another study, a cavity and a line defect were fabricated on the surface of a silicon substrate to capture lung cancer cells.189In another study, 1-D PC slabs obtained from quartz materials were fabricated via NIL. This PC-based platform was used to detect 21 different cancer biomarkers, including HER2, EGFR, and prostate-specific antigen (PSA) with a detection range from 2.1 pg mL−1to 41 pg mL−1.193This multiplexed cancer biomarker platform can function in both fluorescence and non-fluorescence modes, providing flexibility to work with labelled and non-labelled biotarget sensing.5.4 Pathogen detectionRapid identification and quantification of pathogens, such as bacteria and viruses, is important for diagnosis and prognosis in the POC environments at resource-constrained settings. Recently, PC structures have been deployed at the POC for diagnoses of infectious diseases caused by pathogenic agents and toxins.92,109,194For instance, 2-D PC pillars, fabricated on polymer substrates using NIL, were used for the detection of human influenza virus (H1N1) in human saliva. This platform can detect H1N1 antigens at a concentration as low as 1 ng mL−1.93In another study, polymer-2-D pillar PC structures were used to detect L. pneumophila bacteria down to 200 cells per mL.96PC-based platforms can also be used for the detection of viruses such as rotavirus, HIV-1, and human papilloma virus-like particles.92,94,195To detect HIV-1, a PC surface was functionalized with anti-gp120 antibody for capturing HIV-1 ranging from 104copies per mL to 108copies per mL (Fig. 11g–i). In another study, silica microspheres were used to fabricate colloidal PC structures for the detection of multiple mycotoxins in cereal samples.201Although microspheres are fabricated inexpensively as droplets in water–oil two-phase flow, this system still depends on fluorescence measurements and may be subject to undesirable background variation due to the inherent labelling procedure.1965.5 Glucose sensingDetection of glucose holds significant importance in POC diagnostics for diabetics.197,198Although glucose sensors are globally available as POC tools, there is still a need for non-invasive glucose biosensing using new and advanced technology sensing platforms, including PC-based biosensors.199,200Non-invasive monitoring can be achieved by collecting samples other than blood such as sweat, tear fluid, and urine. For instance, a hybrid photonic structure (1-D Bragg gratings) was fabricated from silver nanoparticles and a hydrogel to detect glucose, fructose, and lactate. This platform was tested with urine samples from diabetes patients with a detection limit of 90 μM.41In another study, the poly(hydroxyethyl methacrylate)-based (pHEMA) matrix was UV cross-linked, and silver nanoparticles were dispersed in this hydrogel. A pulse laser was then used to align the silver particles in confined regions creating a periodic structure, which ultimately provided PC properties.201Furthermore, the platform was also tested in artificial tear fluid for accurate glucose sensing (Fig. 12). This platform is unique because it employs inexpensive hydrogels and can be linked to biomolecules by easy conjugation with carboxylic groups. In this study, PC structures were fabricated from polystyrene colloidal spheres integrated with hydrogel for glucose sensing at 50 μM.Fig. 12Glucose sensing from urine using a PC biosensor. (a) Scheme of Ag incorporated hydrogel PC structure. (b) Simulation of a PWS as a result of the pH change. (c) The PWS at varying pH values and its corresponding observable color code. Reproduced from ref. ...Overall, although PC-based platforms have been employed for the detection of glucose with encouraging results, their widespread utilization for glucose sensing and diabetes diagnosis needs to be evaluated for reliable and accurate sensing.6. Surface chemistry approaches in PC-based biosensing applicationsPC-based biosensing platforms consist of an optically active layer and immobilized binder molecules, such as affibodies, nanobodies, peptides, antibodies, and antibody fragments to ensure biotarget capture.157,158,202Depending on the material type used for the optically active layer, binder molecules can be immobilized using various functionalization strategies, including physical adsorption (physisorption), covalent binding, and affinity-assisted coupling. Furthermore, anti-fouling agents play an important role in reducing the non-specific interactions and improving the sensitivity and specificity. In this section, we discuss surface chemistry approaches for TiO2-, Si-, and SiO2- based PC sensors, as well as anti-fouling agents to minimize non-specific binding.Physical adsorption strategies are used to accumulate bio-targets onto optically active layers via hydrogen bonds and van der Waals interactions. By applying plasma techniques, the net charge on a surface can be changed to increase the surface coverage of a biotarget.203For instance, PC waveguide structures with a Si layer were employed to monitor the physisorption of bovine serum albumin (BSA).35In this study, a BSA solution was directly applied to the PC waveguide surface and non-specific physical adsorption of BSA molecules was monitored. Although physisorption is simple, easy-to-apply, and does not require any wet-chemistry or laborious modification steps, it can interfere with other biomolecules in the detection buffer. Furthermore, physisorption is based on weak interactions between the surface and the biotarget, and is therefore not stable and can easily detach when surface charge is altered by changes in pH, ionic content, and temperature.Covalent binding is one of the standard methods for immobilization approaches using the strong chemical linkage that forms between a sensor surface and binder molecules. TiO2and SiO2surfaces are common substrates for optical sensors; however, performing coupling on these surfaces is laborious since it requires layer-by-layer surface functionalization including surface activation, functional group generation, and binder immobilization. Silane-based molecules with a variety of functional groups are commonly used to immobilize biomolecules onto glass surfaces. A standard protocol for silanizing a surface begins with cleaning the surface using a strong oxidizing agent, such as piranha solution (a mixture of H2O2and H2SO4) to increase the density of silanol groups exposed on a surface, which also increases the hydrophilicity of the sensor surface. Then, a silanization agent, such as (3-aminopropyl)triethoxysilane (APTES) or (3-aminopropyl)trimethoxysilane–tetramethoxysilane (MPTMS or 3-MPS), is applied to generate a self-assembled monolayer (SAM), which consists of hydroxyl groups, alkyl backbone chains, and functional tail groups.204,205Alkyl chains enable the height of captured biotargets to be adjusted from the sensor surface, and can also contain active tail groups, such as amine, carboxyl, and succinimide esters to tether binder molecules (Fig. 13).Fig. 13Surface chemistry approaches for PC-based biosensors. Initially, the PC surface (i.e., TiO2) is treated with piranha solution and/or oxygen plasma to increase the hydrophilicity by exposing polar molecules on the surface. The surface is then immersed ...The latter surface functionalization approach provides affinity-based interactions at specific regions on binders and anchor molecules.206However, clinical samples have a complex composition including proteins, lipids, and sugar units that can non-specifically adhere to a sensor surface. Non-specific binding can occur at active, passivated, and untreated areas on the sensor. Anti-fouling agents, including chemical modifiers, proteins, and polymeric substances, serve to prevent non-specific binding and increase the detection accuracy of target molecules. Furthermore, working with biospecimens requires sample preparation steps to avoid signal fluctuations and inaccuracies, considerably increasing the complexity of biosensing assays.207,2087. Current challenges and limitations for biosensors at the POCIn this section, we discuss a number of emerging technologies with respect to challenges associated with current biosensors at the POC. These criteria include label-free sensing, assay complexity, assay time, multi-target detection, read-out mechanisms, fabrication methods, and applicability for clinical testing. We compare PC-based biosensing platforms with up-to-date bio-sensing technologies: nanomechanical sensors, plasmonics tools, electrical sensing platforms, and magnetosensors (Table 2).7.1 Label-free biosensingLabeling of biotargets, often with fluorescence molecules, has been extensively utilized in biosensing applications to enhance signal readout for improving measurements. However, introducing a label potentially adds complexity, increases experimental errors, and presents additional inefficiencies and uncertainties, such as quenching effects and photobleaching.209Additionally, labeling a biomolecule can significantly alter its characteristic properties (conformation, solubility, and affinity).210Considering the challenges associated with labeling, label-free assays can reduce cost, complexity, and time for POC tests by eliminating the use of labels, dyes, and high-volume of reagents.211–213Therefore, there is a demand for label-free, rapid, sensitive and accurate bio-sensing platforms at the POC, which will address the challenges associated with current label-based biosensor strategies. In this regard, PC structures represent a new class of biosensors that hold promise for label-free biosensing with potential applications at the POC.7.2 Assay timeTo be sustainable, emerging technologies need to provide rapid, inexpensive, and multiplexed solutions over existing assays and methods. Some platforms require filtration-type sample preparation steps to concentrate targets in the sample, which also increases assay complexity and time.214From a POC perspective, biosensing platforms need to be fabricated with inexpensive materials and methods using simple and inexpensive production techniques. For instance, some of the biosensing platforms require clean room facilities and multiple chemical etches for their fabrication, which may significantly increase the total assay cost.214The read-out mechanism is another pivotal criterion to obtain reliable measurements at the POC. For instance, nano-mechanical platforms, including quartz crystal microbalance and piezoelectric sensors, are affected by multiple external parameters such as temperature and vibration and require additional equipment (e.g., vibration insulation and temperature control systems) to minimize these external interferences to ensure reliable measurements.215This additional equipment limits the portability and may also increase the cost, thus not satisfying some of the key requirements for a POC device.7.3 Multiplexing capabilityAn ideal biosensing platform needs to detect multiple targets. This feature will provide a wide window to evaluate different targets on a single platform, increasing its applicability for versatile POC testing. To immobilize various antibodies/binders onto a single sensor surface, PC-based biosensor platforms can benefit from antibody printing technologies (Table 2).1937.4 Clinical validationBiological specimens, such as blood, saliva, urine, and sweat, have distinct characteristics. These matrices have various ionic content, ionic strength, pH, and a diverse makeup comprised of cells, proteins, and lipids. Detecting biotargets in biological matrices constitutes one of the major challenges for biosensing. For instance, electrical-based sensing platforms measure electrical potential via different modalities, such as amperometry, potentiometry, and capacitance read-outs. Most of these platforms require replacing the biological matrix with non-ionic fluids, and therefore multi-step flow or centrifugation is required to minimize or eliminate interfering factors for read-out.115,216Ultimately, biosensors need to undergo extensive clinical validation before they can be used at the POC.8. Future outlook for PC-based biosensors at POC diagnosticsThe global biosensor market is valued at approximately US$ 13 billion in 2013 and projected to grow substantially to US$ 22 billion by 2020.217On-site (bedside) biosensors at the POC are poised to transform the healthcare industry as invaluable tools for the diagnosis and monitoring of diseases, infections, and pandemics worldwide. Advances in flexible, wearable, and implantable sensing technologies integrated with responsive materials can potentially connect patients to the clinic, thus providing continuous monitoring, such as glucose sensing for the patients with diabetes at the point-of-need.218,219Due to their characteristics including flexibility (e.g., hydrogels) and integration capability with smart materials (e.g., CNTs and graphene), PC-based sensors will be an asset to the current wearable continuous monitoring tools and sensors.A color shift that can be observed with the naked eye or with the help of a color legend is valuable at the POC. One interesting potential application for PC-based structures is to dynamically change the optical properties in response to environmental parameters, such as geometry, pH, and temperature. An example can be found in nature as suggested by a recent study on chameleon skin, which revealed the presence of guanine pillar-like nanocrystal PC structures.220When relaxed, crystals were randomly distributed, but changed to a square or hexagonally-packed lattice geometry when excited, thereby changing the skin’s visible colors (Fig. 14). Inspired by this example, PC structures could also be fabricated as simple diagnostic tools to produce a color shift against an external stimulus with a subsequent change in geometry. This method may potentially eliminate the need for large and expensive optical devices for biosensors in the POC applications.Fig. 14Spatial arrangements of PC structures in chameleon’s body. (a) The color change of two male chameleons. The left column indicates the relaxed state; the right column indicates the excited state. (b) TEM images of these two states. In the relaxed ...PC structures with more complicated geometries, such as 2-D PCs, are sensitive to changes in the refractive index in nano-and micro-scale volumes. Large wavelength shifts were experimentally observed after binding single sub-micron sized metallic and polymeric nanoparticles.122,221–224Detection of virus particles using these structures are highly promising, since viruses strongly interact with light, and can be easily captured on top of or inside photonic crystals.34,194However, biological detection of viral particles using 2-D PC structures has been difficult due to the low refractive index contrast between water and biological targets. Recent work with human papillomavirus-like particles spiked into serum has suggested that the detection of biologically relevant particles is possible, with a detection limit in the nanomolar range.929. ConclusionDetection of biomolecules at the POC faces multiple challenges, including the lack of centralized labs, limited technical capabilities, the absence of skilled staff, and poor health care management systems (particularly in resource-limited settings). PC-based biosensors represent a novel class of advanced optical biosensors that readily address these drawbacks. PC structures are used as biosensors for cells, bacteria, viruses, and numerous biomolecules, such as proteins, cancer biomarkers, allergens, DNAs, RNAs, glucose, and toxins. These structures can be manufactured with metals, oxides, plastics, polymers, and glass in mass quantities using NIL technology or wet chemical synthesis of colloidal and polymer structures. Recently, PC structures have been integrated with emerging technologies such as smart-phones, flexible materials, and wearable sensors to enhance their utilization as potential diagnostic tools at the POC. However, clinical specimens may require sample preparation steps such as filtration, which may limit the use of PC-based biosensors at the POC. Additionally, complex biological fluids comprising cells and tissues may interfere with the transducer of biosensors and some of the delicate PC structures might experience challenges with the sensing mechanism including read-out systems. In addition, PC structures have been translated to a few products in biosensing, chemical and humidity sensing. PC-based biosensors represent a new class of advanced technology products that can be good candidates for a wide array of applications at the POC.AcknowledgmentsU. D. is a founder of and has an equity interest in: (i) DxNow Inc., a company that is developing microfluidic and imaging technologies for point-of-care diagnostic solutions, and (ii) Koek Biotech, a company that is developing microfluidic in vitrofertilization (IVF) technologies for clinical solutions. U. D.’s interests were viewed and managed in accordance with the conflict of interest policies. U. D. would like to acknowledge National Institutes of Health (NIH) R01 A1093282, R01 GM108584, R01 DE02497101, NIH R01 AI120683.BiographiesHakan InanHakan Inan is a postdoctoral research fellow at the Canary Cancer Early Detection Center at the Medicine Faculty, Stanford University. He is working on microfluidics and nanotechnology-based diagnostic devices and techniques for cancer diagnosis and prognosis for point-of-care applications. He obtained his Master and PhD degrees in nanotechnology. He joined Professor Utkan Demirci’s lab at Stanford University in 2014 as a visiting graduate student and has performed his research in the same group since then. He has 12 years of teaching experience at high school and undergraduate level, where he taught chemistry and biochemistry.Muhammet PoyrazMuhammet Poyraz is a PhD student in electrical engineering at Stanford University and a graduate researcher at the Canary Center at Stanford for Cancer Early Detection. He received his BS degree from Bilkent University, Turkey, in electrical and electronics engineering. He joined Professor Utkan Demirci’s lab at Stanford University in 2016 as a graduate student. He is currently working on photonic crystal and plasmonic based biosensing technologies for point-of-care applications.Fatih InciFatih Inci received the PhD degree from Istanbul Technical University (Turkey), focusing on biosensor design and development for clinical and pharmaceutical applications. He was then appointed as a Postdoctoral Research Fellow at Harvard Medical School and Stanford University School of Medicine. Dr Inci is currently working as a Basic Life Science Research Scientist at Stanford University School of Medicine, Canary Center at Stanford for Cancer Early Detection. His research is focused on creating point-of-care diagnostic technologies, lab-on-a-chip platforms, nanoplasmonic biosensors, and surface chemistry approaches for medical diagnostics. Dr Inci’s work has been highlighted in the NIH–NIBIB, Boston University, Canary Center at Stanford, Johns Hopkins University, JAMA, Nature Medicine, AIP, Newsweek, and Popular Science.Mark A. LifsonMark Lifson is a biomedical and computer engineer currently working as a postdoctoral research fellow at Stanford. He obtained his Bachelor of Science in computer engineering from the Rochester Institute of Technology, and his Master of Science and Doctorate from the University of Rochester in biomedical engineering. His research interests include developing ultra-sensitive sensors for biomarker detection. He has expertise in photonic crystals, microfluidics, localized surface plasmon resonance, and smart colloidal nanoparticles.Brian T. CunninghamBrian T. Cunningham is the Willett Professor of Engineering in the Department of Electrical and Computer Engineering at the University of Illinois at Urbana-Champaign, where he also serves as the Director of the Micro and Nanotechnology Laboratory. His research interests include the development of biosensors and detection instruments for pharmaceutical high throughput screening, disease diagnostics, point-of-care testing, life science research, and environmental monitoring. He has published 160 peer-reviewed journal articles, and is an inventor on 83 patents. Prof. Cunningham was a co-founder of SRU Biosystems in 2000, and founded Exalt Diagnostics in 2012 to commercialize photonic crystal enhanced fluorescence technology for disease biomarker detection. Acoustic MEMS biosensor technology that he developed at the Draper Laboratory has been commercialized by Bioscale, Inc. Prof. Cunningham’s work was recognized with the IEEE Sensors Council Technical Achievement Award and the IEEE Engineering in Medicine and Biology Technical Achievement Award. He is a member of the National Academy of Inventors and a Fellow of IEEE, OSA, and AIMBE.Utkan DemirciUtkan Demirci is an Associate Professor at the School of Medicine, Department of Radiology, Canary Center at Stanford for Cancer Early Detection. His research interests involve the applications of microfluidics, nanoscale technologies and acoustics in medicine, especially portable, inexpensive, disposable technology platforms in resource-constrained settings for global health problems and 3-D biofabrication and tissue models including 3-D cancer and neural cultures. Dr Demirci has published over 120 peer-reviewed publications, over 150 conference abstracts and proceedings, 10 book chapters, and edited four books. His work has been recognized by numerous awards including the NSF Faculty Early Career Development (CAREER) Award and the IEEE-EMBS Early Career Achievement Award. He was selected as one of the world’s top 35 young innovators under the age of 35 (TR-35) by the MIT Technology Review. His patents have been translated into start-up companies including DxNOW and Koek Biotech. Some of these technologies are clinically available across the globe.

Original Question: The egyptologists [sic] were debunked in 2014. Why are the anti-Mormons still saying Joseph Smith mistranslated the characters?Answer: On doing some further research, and asking questions as part of said research, the person asking the above question was referring to the understanding of the situation by one Paul Gregerson, who came up with it back in 2014. The short answer is that few critics have watched that YouTube video. Those who have done so do not appear to accept the information presented as a refutation, and that would appear to be the reason why anti-Mormons still are saying Joseph Smith mistranslated the characters. But here is the thing. A number of Anti-Mormons I have known, and/or with whom I have had personal conversations, over the years have turned out to be quite dishonest. Many years ago, I was privy to a conversation between a Latter-day Saint and Dick Baer (an anti-Mormon with a flair for the sensational). It was a rather lengthy discussion over the phone, with back and forth argumentation between the two of them (though not at all heated discussion as one might think would be the case). Unfortunately, this phone call was not recorded so I cannot give more than anecdotal information regarding it.But, after over an hour of back and forth argumentation, Dick Baer actually came out and admitted to the person with whom he was discussing his questions on “Mormonism” (in my hearing) that his questions had been answered completely, and that no “Mormon” ever had been able to answer any of his questions before—until that day. Yet, even after saying that (and having to go to the bathroom, as did the other person on the phone, thus ending said conversation amicably), I became aware that Dick Baer gave one of his signature presentations at a Baptist church in Pomona, California, the next day or so after the phone conversation. And when I watched a recorded video from the said presentation, I saw that he again asked the very same questions that he admitted had been answered, and then once again claimed that “no ‘Mormon’ to date has ever been able to answer these questions.” Hmmm. Well, that is not what I heard him say! So why did he do this?Some anti-Mormons seriously are in it for the money. They don’t care about the truth so long as they can make a buck from their labors. For some of them, the ends justify the means—even the use of deliberate deception! A fellow I know once also had a discussion with Ed Decker, during lunch. He asked Ed how he could continue doing what he did, knowing he was lying about various things. His simple answer said it all: “The end justifies the means.” I was astonished to hear that report, but not entirely surprised by it. Decker probably would deny this ever happened.But many of those concerned for the spiritual health and perceived fate of Latter-day Saints are perfectly happy to fork over much money for the works of such individuals, if they think it can help Latter-day Saints come to their version of Christ (based on their post-Nicene interpretations of the Bible). But I digress. And I found Gregerson’s approach an interesting approach to the subject matter, namely, the idea that Gregerson, as one who believes Gregerson’s presentation says, “debunked the Egyptologists by demonstrating proper interpretation. Proper interpretation is that Joseph Smith translated in reverse back to a biblical text, the original.”However, it seems not quite enough to get the job done, in my opinion. There is far more going on than a putative translation “in reverse back to a biblical text.” I’m not sure I can support the entire content of the video approach because of what I know of the situation from careful study of all the documents in question. Some of his presentation is interesting. He has since apparently deleted his original 2014 video and has updated and expanded his approach, as of last year. See the following video for Gregerson’s current but related and expanded approach to the issue.Let the reader take a look and make up one’s own mind regarding the presentation. My approach is a bit different, of course, being based on the evidence of the documents. But, thing is, many of the critics who adhere to their various approaches to the Book of Abraham aren’t readily going to change their minds. Some have left the Church over their objections regarding the Book of Abraham. A number of those who left, and have decided to stay away, are heavily invested in their primary reason for leaving. Many will not give it up easily. Or, so it seems to me. Their objections also by them have been considered to be among the best evidence against the Book of Abraham, and thus against the Church, for many years. So much so, that some professional critics in recent years have encouraged their adherents in apologetics conferences to focus more on the Book of Abraham to break faith among the Latter-day Saints who may be susceptible to their approach.But they indeed do have serious issues with their various approaches to the Book of Abraham, as recent archaeological and other documentary evidence has begun to show, not the least of which is the fact that they have been relying on portions of documents that they interpret as showing a so-called modus operandi of the “translation process” of the Book of Abraham. And they thereby claim that because Egyptian characters from the Joseph Smith Papyri are those also found in the Document of Breathing (or Book of Breathing Made by Isis), and that Egyptologists have shown that Joseph Smith was “wrong” based on a literal reading of said characters, the Book of Abraham is “fraudulent,” and that because of this the Book of Mormon also cannot be trusted.Above all, they must do all they can to try to dismiss any plausibility of the existence of another portion of scroll that contained the Book of Abraham. Some have come up with a formula that they claim shows that there cannot have been any more scroll, to lend assistance to said claims. But that is not what we see from eyewitnesses to the exhibition of the papyri during and immediately after the Prophet Joseph Smith’s lifetime. The rest of this answer is drawn in large part from comments I have made in replies to others. And herein is a major thorn in the sides of the critics’ claims.According to the combined testimony of four critics of the Church, three in the days of Joseph Smith (Charles Adams and Josiah Quincy together, and a minister whose name escapes me at the moment), and one directly afterward (Charlotte Haven), the fragments that now are extant were mounted under glass, and a long scroll in addition identified as the source of (and as containing) the Book of Abraham, were exhibited separately. This separation of materials had taken place sometime between 1837 and 1841.None of the “nonsense” in the Grammar and Alphabet of the Egyptian Language the critics love to cite in part can be tied directly to Joseph Smith. In the manuscripts that do have his handwriting, it was nothing more than a copy of two prior documents, with some modifications to the material and format, indicating a change of approach. This material was copied in part into the GAEL book, and expanded further, but the material in the separate manuscripts not long afterward was aborted and abandoned in favor of the book (which itself would be aborted and left unfinished not long afterward).The same goes for the Book of Abraham manuscripts from 1835. These also were aborted. English text was copied from them, and then these three manuscripts were set aside as translation continued without the use of Egyptian characters. The so-called “process” (but which itself actually was comprised of two differing methodologies) was abandoned completely. The matching project that had begun during the time of the translation of the Book of Abraham was discontinued.The next three manuscripts (previously thought to be two but now known to be three (or, possibly four), two of which were part of the printer’s manuscript used for the Times and Seasons), had not one Egyptian character on them with English text, whatsoever. Previous Kirtland Egyptian material on the top of one of the pages of these manuscripts was erased before continuing (erasures always are intentional). The book that was titled Grammar and Alphabet of the Egyptian Language also was aborted and left unfinished, with large swaths of blank pages as well as one that was lined but left unfinished.In November of 1843, Joseph Smith again would suggest preparing a Grammar of the Egyptian Language, which never came to fruition. Something had happened in 1843 to cause him to abandon the project and leave it unfinished. There was no way that the material in that volume could have been prepared for publication. And, if he still had accepted it by November 1843, what made him suggest preparing another one if the one already prepared was acceptable to him?Fact is, we also now know that the scroll identified by critics of the Church as containing the Book of Abraham, along with the vignette that became Facsimile 3 still attached at the front of the remaining scroll, really was destroyed in the Great Chicago Fire of 1871. We know this from the testimony of the last Egyptologist to see the remaining scroll, as well as museum manifests. And there is yet another issue.The following is a Document of Breathing Made by Isis of the type owned by Joseph Smith. This example now is known as the Lafayette College Papyrus. It belonged to a person named Her-Nuty.If the vignette that was at the end truly was the end of the scroll of the Document of Breathing in the case of the example owned by Joseph Smith, as critics have long maintained, there would be absolutely no way at all that there could be additional scroll if the Document of Breathing (also known as Book of Breathing) was the only document on the scroll. Yet, a separate scroll was identified as a scroll by three hostile eyewitnesses (all three combined stating that Mother Smith and Joseph Smith both told them that the separated scroll was the source of the Book of Abraham), as well as by the last Egyptologist who laid his eyes on it in 1856, before its move to the Wood’s Museum, in Chicago.Only the fragments formerly mounted under glass, along with a handful of other fragments, now are extant. And not even all of those fragments are any longer extant. Sections of even the Document of Breathing text now are missing. And there is even more interesting evidence that has come to light over the years regarding these Egyptian-related materials among the Kirtland Egyptian Papers.And, actually, the documents were damaged when they were opened, which was before Joseph Smith had them. They were damaged further from use. What I mentioned above about the “nonsense” was with respect to the Grammar and Alphabet of the Egyptian Language. It is a mix of some interesting things with a lot of “rambling nonsense.”As to Theodul Deveria, one the critics’ favorite old Egyptologists, he never saw the Papyri nor any of the Kirtland Egyptian Papers. His arguments were based on his opinions regarding the printed Facsimiles, combined with his own assumptions from previous experiences with inscriptions and other documents only tangentially connected to the Book of Breathing. He himself got a number of things wrong in the process of pontificating (but that is another conversation for another time and place).The current papyrus fragments, as they are extant, don’t appear to have anything to do with Abraham, it is true—at least on the surface. But the scroll identified as containing the Book of Abraham now is gone, so there is no way to say definitively that this lost document says anything, or even nothing, about Abraham. It gets worse than this, however, for the claims of the critics.You see, dear reader, there was a matching project that involved several people, who attempted to match up Egyptian characters from the papyrus fragments to the English text of the Book of Abraham as the translation proceeded. But this approach was abandoned the same year it started. It didn’t even all start at the same place! But even with that abortion and abandonment of the matching project the Book of Abraham continued to be translated. Thus, it couldn’t possibly have been the modus operandi, or the so-called methodology of translation, as the critics have claimed. Otherwise, it would have continued to be the methodology. It gets worse still.Evidence from the Hypocephalus itself seems to imply that Joseph Smith may no longer have considered the Egyptian characters content of the manuscripts of the matching project valid by the time 1841-1842 rolled around and the translation began again. And, in point of fact, only the English text was copied from one of the older 1835 manuscripts, and slightly reworked, into a working manuscript for the Book of Abraham sometime in 1841–1842. Take a look at the following composite graphic of Facsimile 2 and graphic snippets from the longest of the Book of Abraham manuscripts with attempts at matching Egyptian characters.Did you notice the lines of characters from Joseph Smith Papyrus XI? Following are the same characters, as they were written in the 1835 document, alongside English text of the Book of Abraham. (These photographic snippets are borrowed from the fuller photographs at the Joseph Smith Papers Project website.)The above manuscript segments seem to imply that some level of meaning was understood—at least, it would appear so, at first glance. And this forms the entire foundation of the critics’ claims against the Book of Abraham! But then Joseph Smith used characters from the same papyrus fragment section claimed by the critics to be translated previously, and then gives no meaning! If he really had accepted the meanings already given, why use fragments of the same texts, and then give no meaning, and then say that they could not provide the translation thereof until the own due time of the Lord, as he did for the ring of text (figure 18) in Facsimile 2? Didn’t he already have the meanings, if he accepted them? And that is the point.The fuller evidence suggests that Joseph Smith may not have accepted much of the previous work any longer by the time 1841–1842 rolled around. Why? One of the manuscripts from 1835 shows an early abandonment of attempts to match the characters to English text, dropping two sets of Egyptian characters that another manuscript has for similar text. (Again, from the Joseph Papers project website.)This manuscript contains a dittographic text, meaning it was copied from another manuscript, and copied twice during copying. But notice also how the column of Egyptian characters now is ignored and abandoned? Now, compare that to the following, which is the longest matching project manuscript (also from the same site).Notice the difference between the above? Two characters are seen in this manuscript that are omitted from the manuscript page in the photo previous. Unfortunately, the previous document is not complete, and may be missing a page or two. But enough is extant in the example in the photo previous to this one to show the example of the abandonment of the approach by the scribe who worked on that manuscript. This also shows a degree of independence from the other manuscripts, as the scribes appeared to cease working simultaneously during this phase of the translation activity’s failing matching project experimentation. The scribe in the above photo appears to continue the approach after the other scribes stopped participating (as shown in the above snippets from Manuscript C), until work ceases on this manuscript as well, as the following final page of Manuscript C from the Joseph Smith Papers project website also shows.And that was the end of that! That is the end of the use of attempts at matching characters from the papyrus roll of the Document of Breathing to the English text of the Book of Abraham, which ends at Abraham 2:18. And, one of the working manuscripts even has material erased from one of the pages before being used for the working and printer’s manuscripts for the Book of Abraham. This can be seen in a closeup of the working manuscript prior to creation of the printer’s manuscript of the Book of Abraham, as seen from the following closeup photo from the said extant Book of Abraham working manuscript.If the reader looks carefully at the top of this page, the reader can see erased text in the top margin of this page in the manuscript. This paper was repurposed for the working manuscript. It should be remembered that erasures are always purposeful. This above manuscript appears to have been copied from the older, longer 1835 manuscript. Note from the full end page of this working manuscript that no Egyptian characters are used from the older work (also from the Joseph Smith Papers site).The above contains the English text seen in the last page of the abandoned matching project manuscript containing the same verses. No Egyptian characters whatsoever are used in this manuscript. After this, no Egyptian characters are matched with Egyptian text in either the working manuscript or the printer’s manuscript of the Book of Abraham, but the translation of the Book of Abraham continued, without any further matching of Egyptian characters after 1835, as shown from the following pages of what appears to be the extant portion of the printer’s manuscript of the Book of Abraham (also borrowed from the Joseph Smith Papers website photo collection).The above manuscript pages contain Abraham 3:18–26. From the above, it can be seen that the translation continued years after the 1835 matching projects and attempted reverse engineering of Egyptian grammar from various characters in the papyri (and from elsewhere, such as a letter from W. W. Phelps that predated the purchase of the papyri by about six months’ time). And again, no Egyptian characters. Just inspired English text.Critics say that “many actual Egyptologists have confirmed the same” claims of the critics. But as mentioned and shown above, there is a rather serious problem. No Egyptologist but one ever has seen the remainder of the scroll that was identified, by Joseph Smith and Lucy Mack Smith, as containing and as being the source of the Book of Abraham. Only one. His name was Gustavus Seyffarth. And he did not translate it. And his identification of the remaining scroll was itself a based on a mistranslation.No, the truth is that many Egyptologists have pontificated on something they have never seen, and based only on what they would see in the Facsimiles, which Facsimiles themselves weren’t actually ever translated! It is true. Joseph Smith never actually translated the contents of the Facsimiles. He did offer explanations but no actual translations. Even the word “translation” used in the explanations of Facsimile 2 has the definition of “explanation,” as can be seen in Definition 7 of the entry “Translate” in the second volume of Webster’s 1828 An American Dictionary of the English Language. Here. See for yourself:But the critics base their primary argumentation on the failed and aborted matching manuscripts, which don’t even agree among themselves as to methodology (one manuscript, Manuscript C, starts out with two differing attempts and methodologies), beginning, ending, and one of which even abandons use of Egyptian characters where another has them! But they generally always seem to ignore the later working translation manuscripts that contain no Egyptian characters in them, whatsoever.But this very foundational evidence they claim is against the Book of Abraham also is based in large part on work that further evidence shows Joseph Smith himself may have rejected after 1837, as shown by the above composite graphic of Facsimile 2 and accompanying photos of manuscript snippets, and possibly also his cutting apart of the long scroll! And, funny thing. One Egyptologist even wrote the following about the overall situation (which is one of a couple reasons why professional critics of the Church eventually stopped using him as a source to attack the Book of Abraham):“A valid counterargument for the faithful would be that we Egyptologists can claim no inspiration. We can only scrape the surface meaning. If Joseph Smith was a prophet, he was an instrument of divine authority, so that he might find the deepest meaning. Although our work deals with fact, we must respect faith. As the Protestant world survived the Higher Criticism of the Bible three generations ago, the Mormons will survive this criticism.”(John A. Wilson, in Thousands of Years: An Archaeologist’s Search for Ancient Egypt (New York: Charles Scribner’s Sons, 1972), 177.)Many questions arise from the state of the materials involved. Critics don’t feel that the 2014 (or 2017-2019 updates and expansions) material in the video refutes anything. But they also continue to rely on old, outdated, and recycled information to form the foundation of their own derivative work. But it was not until fairly recently that some of the additional nuances came to be known, that now appear to be tearing out that foundation. This includes various pieces of archaeological evidence. One would think that if the Book of Abraham were a completely made-up production, no evidence whatsoever supporting the assertions of the English text of the Book of Abraham ever would come forth. Not even a little bit. Not ever.For example, at least one of the old Egyptologists made much of the Book of Abraham having non-Egyptian deities depicted like Egyptian ones, and claiming that Egyptians did no such thing as syncretize the deities of foreigners in the dress of their own gods and goddesses. Some of this evidence has been preserved to our own day. Not only was the patron goddess of Gebla (ancient Byblos) considered by the Egyptians to be “Hathor of the West,” she also was dressed to look like Hathor! And much further evidence has been found that the Egyptians indeed did what the Book of Abraham implied about the practices of Egyptians and others in the Ancient Near East. The Brooklyn Museum has in its collection an inscription of Egyptian pair statues of Ramses II and a goddess he worshipped.One clearly can see the goddess (or, “Lady (of) Heaven”) Anat standing behind Ramses II. The inscription so names her as “Anat Lady (of) Heaven (and) of Ramesessu Meri-Amun.” But the manner of dress she is wearing is that of Osiris! And there are numerous examples of other such happenstances all though later Egyptian history as well, such as the adoption of Resheph as Min-Amonrasonter (of Joseph Smith Papyri and Theban fame).In addition, there is an interesting phrasing in the Book of Abraham. This text is as follows:13 And he said unto me: This is Shinehah, which is the sun. And he said unto me: Kokob, which is star. And he said unto me: Olea, which is the moon. And he said unto me: Kokaubeam, which signifies stars, or all the great lights, which were in the firmament of heaven.(Abraham 3:13, bold and italic emphasis mine)This is one of those things that some critics would like to dismiss as purely a lucky guess on the part of Joseph Smith. Decide for yourself what you make of the following information. Following is an Egyptian phrase-word.This phrase-word can be seen in multiple places in the Coffin Texts, at least three of which examples appear in three variants of Spell 18 of the Coffin Texts alone. I cite one of these below, with one of the three in that one text marked in red (there are many other examples of the same in multiple spells of the Coffin Texts, as stated above, but one should suffice). The following comes from Adriaan De Buck and Alan Gardiner, eds., The Egyptian Coffin Texts (Chicago: University of Chicago Press, 1935), I 53.That is very close to the claim of the Book of Abraham that Shinehah represented the sun. It also is close in sound. The above marked phrase-word is transliterated š(j) nḫꜢ (which would be pronounced something like shi-nehah). And, in point of fact, the above shown Egyptian Hieroglyphic phrase-word actually refers to the path taken by the sun in the watery heavens (lit., “Waterway of the Winding”; see š nḫꜢ in Rami van der Molen, A Hieroglyphic Dictionary of Egyptian Coffin Texts [Brill: Leiden, 2000], 599). Watery heavens, you say? Well, the Egyptians really did think of the skies that way, just as the Book of Abraham stated. I refer the reader to figure 12 in Facsimile 1 and Figure 4 in Facsimile 2. And there is more. We find the solar boat of Horus-Sokar connected with the number 1,000 in Facsimile 2, as well as with the heavens. We see from multiple ancient sources that the Egyptians actually thought of the skies as a watery place, and that they even used nautical terms for the movements of the sun, stars and planets through the skies. But things get even more interesting than the above.The solar boat also was known as the “ship of 1,000 cubits” by the Egyptians, or as one of the Coffin Texts puts it: “ship of 1,000 cubits from end to end, and he sails it to the stairway of fire” (Coffin Text 162 (II, 403-404)), or, as Faulkner renders it: “a bark of 1000 cubits over all, I will navigate in it to the Stairway of Baking…” (R. O. Faulkner, The Ancient Egyptian Coffin Texts, 3 vols [Warminster: Aris & Phillips Ltd., 1973–1978], 1:140). Either way, it really was connected with the number of 1,000 by the Egyptians. Where on earth did Joseph Smith get something like that? The Coffin Texts weren’t published until many years after Joseph Smith’s death. No Dictionary of the Egyptian Language contained such information until very recently, at least, long after the death of Joseph Smith. And we know Joseph Smith couldn’t read Egyptian on his own. So, where did he get it, and how did he get so close?I’ll have much more information than the above in my forthcoming book on the subject of the Book of Abraham and the Kirtland Egyptian Papers.{Note: Someone calling himself “Ray Watson” suggested that I edit my answer to add information about deciphering the Egyptian language, and included in his edit suggestions a series of paragraphs headed by the word “Except” to imply that I was wrong, and that Joseph Smith could have known the above information from the Coffin Texts I mentioned. I rejected his edit suggestions upon the following grounds:Apparently, the person making the edit suggestions did not appear to know the differences between the Coffin Texts and the popularly so-called Book of the Dead. Even if Joseph Smith had somehow come across knowledge of how to translate the “Book of the Dead” the hard way via the use of a dictionary, it would not been of help to Joseph Smith in dealing with the Coffin Texts (see points 5 and 6, below).As to Joseph Smith knowing the above information, the same person also claimed that the Egyptian language was easily deciphered by the 1850s, and the person suggesting the edits supplied a link to information on a person (Emmanuel de Rougé) who had made it so, and also named Lepsius and his work. Here is the problem with part of said assertions. Joseph Smith was martyred in 1844.Here is another problem. The Book of Abraham was dictated, in part, to scribes in 1835, and the portion containing the word in 1841–1842. The Book of Abraham originally was published in March of 1842, in the Times and Seasons. The earliest known appearance of the word Shinehah as a code name (along with Enoch) was in 1835, in Revelation Book 2 and published in the 1835 first edition of the Doctrine and Covenants. (But it was not defined as having connection to the sun until 1842.) All still well before any published work of the 1850s, and the phrase-word in question does not appear in the 1842 work of Lepsius.Another problem is that the contents of the Coffin Texts have quite a number of differences from the content of the Book of the Dead, so any limited vocabulary of the “Book of the Dead” available at the time in question would not have been helpful in deciphering the Coffin Texts and picking a word to use. While the content differs substantially there still are some parallels in a number of the texts, as the Coffin Texts are ancestral to the “Book of the Dead” and stand between the Pyramid Texts and the “Book of the Dead.” However, these don’t contain the phrase-word in question (see chart at bottom of these points that is part of a work in progress [based on earlier comparative work] and formatted as code to preserve the layout).And, if the words in the phrase-word in question above had been known in that form in the time of Joseph Smith, they would have been in Egyptian Lexicons and Dictionaries from the period, as well as in the standard Lexicon, WÖRTERBUCH DER AEGYPTISCHEN SPRACHE, that was published later. De Buck did not publish his Coffin Texts volumes in seven of the eight volumes until 1961 (with the first volume published in 1935, still far too late to have been of use to Joseph Smith), and the WÖRTERBUCH had already been published in the five main volumes of the twelve volumes before that year, in October of 1931. In point of fact, the phrase-word was not found in the expected locations in the WÖRTERBUCH for the above reasons. I know because I have a complete set of the print volumes, and consulted said work prior to writing my previous comments upon which my answer was based.The vocabulary of the Coffin Texts, in point of fact, finally was published by Brill on February 9, 2000, as Rami Van Der Molen, A Hieroglyphic Dictionary of Egyptian Coffin Texts, in Series Probleme Der Agyptologie, 15. Before that time, a lexicon that included the full vocabulary of The Egyptian Coffin Texts did not yet exist in the public consciousness where Joseph Smith could have gotten access to said knowledge. More information about said volume can be seen at A Hieroglyphic Dictionary of Egyptian Coffin Texts | Brill.Coffin Texts correlated to Book of the Dead Texts relative to the phrase-word š(j) nḫꜢ (Book of Abraham: "Shinehah"):  Coffin Texts Book of the Dead ________________________________________  CT 18 (I 53) BD None Extant CT 61 (I 259) BD None Extant CT 62 (I 270) BD None Extant (except misplaced title of CT Spell 93 (phrase-word not present in title; BD 2, 65a (phrase-word not present) CT 163 (II 405) BD None Extant CT 214 (III 174) BD None Extant CT 241 (III 326) BD None Extant CT 268 (IV 1) BD None Extant CT 285 (IV 35) BD None Extant CT 305 (IV 59)* BD 164 (apparently composed and used during the Late Period (Ptolemaic), but published by Lepsius in 1842; phrase-word not present) CT 347 (IV 380) BD None Extant CT 393 (V 67) BD None Extant CT 418 (V 253) BD None Extant CT 473 (VI 15) BD 153 (phrase-word not present) CT 474 (VI 26) BD 153 (phrase-word not present) CT 479 (VI 42) BD 153 (phrase-word not present) CT 582 (VI 199) BD None Extant CT 905 (VII 111) BD None Extant CT 987 (VII 194) BD None Extant CT 1129 (VII 458) BD None Extant  *Attested as mr nḫꜣ (but may be badly written). There simply was no way that Joseph Smith could have had access to said material by the standard means available at the time. Nor had he any possible access to the Egyptian Coffin Texts, from which he could have obtained the phrase-word in question. And, had he been able to do so, he would not have been able to use any printed source to help him pick the phrase-word in question, as he could not read Egyptian on his own and works that could have been helpful to him in that endeavor were not published until after publication of the Book of Abraham. Anyone claiming to the contrary easily can submit source and page number, and I happily will reexamine the matter further.And one final thing. It seems that critics of the Church and of the Book of Abraham have gotten so uppity over the above information, and other data like it, that they have attempted to get the information deleted, collapsed, and have vandalized the question by merging it with unrelated questions, and failing that thus far, some of the more vocal have resorted to the only thing they have left in their arsenals: argumentum ad hominem. Yes. We all know what that means regarding their arguments. Rather than engage the arguments themselves, and attempt to refute them, they instead handwave and merely engage in logical fallacies.Also: Edited answer to reflect the most up-to-date information and transliteration regarding the phrase-word in question in the above.}