Ceas Iii: Practice & Management Of Occupational Ergonomics: Fill & Download for Free

Even though Raghuram Rajan has become a sort of a controversial figure in the recent times, unnecessarily delving into political statements in the last couple of years (Today is Nov 06, 2019), but after a careful analysis, I must say he has been one of the best Governors the RBI has ever seen, and let me tell you why.Dr. Raghuram Rajan, Governor, RBI - Sept 04, 2013 to Sept 04, 2016.First, let’s set the context of early 2013 so that you can appreciate Rajan much better.UPA Government was undergoing lots of scams, including 2G, commonwealth and what not. The Government had lost its credibility and people had become restless.Anti-Corruption Movement of Anna Hazare was going on for the Lokpal, and the entire country was on the streets, marching for a clean Government.The rupee was at its lowest ever. (Rs. 69 per dollar, which was shocking at that point of time)The Indian economy was named one of the “Fragile Five” and was seeing a downward sloping trend.Retail inflation was touching 9.84% in mid-2013. (It was way too damn high)Our ForEx reserves were at a 03-year low, bare minimum.The Indian banking system was rotting.RBI was just another Government body of boring bankers and old bureaucrats. The Indian youth didn’t care much about politics or banks at that time (when the scams were about to break).The tenure of all RBI Governors was 05 years, and it was a post given to almost retired bureaucrats, usually a resting retirement spot of old IAS officers.There was no much sheen for RBI, it was like the current CSO or the CAG. CAG rose to prominence after the 2G scam, and RBI was seen as a dull boring numbers job. (The way we see CSO now as, just statistics, blah)Raghuram Rajan then was an internationally famed finance wizard, the youngest Chief Economist at IMF, on his way to get a Nobel Prize, the only one to predict the 2008 financial crisis, a widely respected figure teaching away at Chicago Booth.India was restless, PM Modi was not yet made the Prime Ministerial candidate yet, he was in competition with Nitish Kumar (NDA was actually considering Nitish Kumar for the job, this was way before Modi became famous) - I had written an article in April 2013 on this - Akand Sitra's 2013 postWith no answer in sight, us 90s kids were restless due to the incompetence of the Indian Government, a drowning economy in 2012, so many scams, falling rupee, no Modi in sight yet, and all hopes were lost.This was when PM Manmohan Singh went to Rajan in early 2013 and asked to come back to India to join as the RBI Governor.Rajan was already the CEA to the Singh Government and was happily teaching and writing research papers for the IMF, but he agreed to take on the job and wanted to bring a lot of structural reforms to the Indian economy.It was announced in early August 2013 that Rajan would become the next RBI Governor.We were preparing for UPSC Civil Services examination then, so we were following the economic and political news very very closely then, and I distinctly remember the Sensex and Nifty jumping by over 10% just by the announcement of this News.The famous US-based Rajan, a renowned economist of IMF was coming to work for India in a full-time capacity. All of us waited with our bated breaths to see what magic this man could do. And we started following all RBI circulars and all RBI notifications very closely.Sept 04, 2013 - Raghuram Rajan takes over.He brought charisma and sheen to the other-wise boring RBI job. He was called the rockstar Governor, right from his first day. Rajan, with his suits, new fresh western ideas, and intellectual lingo made us common Indians look at him with wonder.But we were no fools. All show and pomp was over, now we needed raw actions, we were a bit skeptical what this westerner would do to India, without really understanding or knowing the ground realities? What would this IMF fellow do to the traditional RBI?We watched his every move with suspicion and were ready to critique every single this he did. Not just us UPSC aspirants, but the entire media, and the entire country indeed. All cameras were on RBI.And then his magic began.In his 36-month tenure, he brought a new fresh idea almost every two months. His RBI circulars and notifications would be in such detail that the idea was so well-refined and it stood out like poetry. I will give a list of all new reforms he brought in, and all of us studied each of them in detail to understand how they would have consequences on the Indian economy.Sept 2013 - From the moment he became the captain of the ship, his first duty was to stabilize the Indian economy - Fight rising inflation and falling rupee first.He announced the sole duty of RBI from now on would be complete focus on “monetary policy” and his goal would be to contain the inflation within the range of (2 to 6%) or more famously, the (4 +/- 2) rule.Oct 2013 - He started his tenure with an out of the box solution to enable banks to convert their FCNR deposits into rupees at a much lower cost, which allowed the inflow of foreign exchange into India, thereby braking the falling rupee effectively.It is not simple to counter such challenges in any economy that was struggling to move ahead. Clearly, it was time for some radical movements. This is exactly what Rajan proved by his announcements.Nov 2013 - Rajan took complete control of the interest rates (repo, reverse repo, MSF etc) to control the rising inflation. He started increasing the repo rates.Narrowing the LAF facility (Liquidity Adjustment Facility) ratios to further control the inflation crises.Till 2013, there was a 30-year old tradition that the difference between the repo and reverse repo rate would be 100 basis points exactly. Noone knew why. We were byhearting the rates, saying if repo was 5%, then reverse repo would be 4%, and the MSF would be 6%. Rajan asked why?Dec 2013 - He said why such a huge difference of 100 basis points even existed, and we need to start narrowing this width. From then on the difference between the repo and reverse repo started decreasing further. (Currently, repo is 5.15 and reverse repo is 4.90 - A difference of 25 basis points). This changed the traditions forever, he questioned the prevailing thinking which most of us took for granted.NPA Problem - Asked the banks to start cleaning up their NPAs. Till now, no one cared about the bad loans that the banks were holding, and not many were even aware of it. He brought the term “ever-greening” of loans to India, and I remember editorial articles on this new term, and it was shocking to see such practices.Identification of the problem itself and bringing the news to the public was a huge impact Rajan had.Jan 2014 - AQR - Asset Quality Review - As RBI is a regulatory body, Rajan said that all the banks would get their assets checked and they would be classified properly. Many banks especially Public Sector Banks had given loans to politicians, crony-capitalists, PSL lending, high NPAs and were structurally very ill.By bringing AQR, by classifying them into standard, sub-standard, doubtful, loss, NPA, SMA1, SMA2, SMA3 and many more such terms, Rajan brought clarity and discipline into banks.Banks started showing more and more NPAs on their books. Till now people thought the banks were doing fine, but this cleaning up of banks showed that the loans which were bad were not even being identified properly.Mar 2014 - Gold Bonds - Many Indians buy gold, lots of it and store it in their homes. RBI has to import gold to satisfy the Indians' demand for gold. This was lowering our ForEx and in return, the gold wasn't being used, it was just stored. This was a huge issue that we didn't even know we had. Rajan identified this and brought about something called the Gold bonds. We could buy the bonds instead and store it, and the RBI need not really import gold for it, and we could be safe as well.The Gold bonds move reduced our imports, and saved some ForEx and strengthened the rupee directly.May 2014 - Inflation-Indexed Bonds - Most of the bonds are not usually indexed to the inflation, so during a slump, noone would buy bonds and the economic activity would stall. By indexing the bonds to the inflation rate, Rajan would stimulate investments, bring out idle money sitting in the lockers and start fuelling the economy.May 26, 2014 - Narendra Modi becomes the Prime Minister of India.July 2014 - Bring in international best practices to Indian RBI so as to increase RBI’s compliance with the Basel III norms (Learn about Basel III) - This would increase RBI’s stature in the international economy as the central bank gets more standardized.August 2014 - Asset Restructuring Companies - RBI has given more power to ARCs to buy NPAs from the corporate banks, modify them and then sell them at a profit. This way the bad loans are removed from the bank’s balance sheet and they become healthy.October 2014 - First Modi - Rajan Clash. Modi Government asks Rajan to reduce the interest rates so that the growth can be given a boost by cheaper loans. Rajan disagreed. He had said that if he reduces the interest rates now, and the loans get cheaper, then the inflation will rise rapidly again. Any growth-related measure in this current situation should come from the fiscal policy of the Government, and not from the monetary policy of the RBI. Growth would be sustainable if it comes from investments, and not by giving cheaper loans.Rajan’s logic made perfect sense, but nobody stands up to Modi. Especially not a lowly RBI banker, and definitely not some foreign-studied super-hero. And Rajan was gaining too much attention and the common citizens were hailing him as a messiah of the poor.November 2014 - Banks Boards Bureau - An independent body should be constituted which selects the heads of the PSBs’ board members. This way no politician or businessmen can have their men on the board of banks. That way no bad corporate loans can be given easily. This was an attack on the so-called “phone banking”, where a politician or a businessman would call up a PSB and coerce them to give large loans to themselves. This would solve nepotism and favoritism in appointing Bank Chairmen.Guess who would hate such a bold move? Politicians and Businessmen, yes.No RBI Governor till now in the history of India had the balls to stand up to politicians, corporates, businessmen and criminals - All at once. Rajan did.Rajan wins the Central Banker of the Year Award.The Friction - 2015Rajan still had considerable political pressure to toe the line, and to reduce the RBI’s interest rates. As Rajan had complete control on the rates, he did not budge. He said the economy is just getting its inflation under control, we need this just for a little while to completely make it stable.Feb 2015 - Creation of the Bharat Bill Payments Systems. And start working on the UPI (Unified Payments Interface) - Works starts now and gets formally launched a year later, in April 2016. Rajan said the future of the country would be in digital payments and in a cashless society. He brought in important people like Urijit Patel (then RBI Deputy Governor, goes on to become next RBI Governor) to work on NPCI’s UPI and also Viral Acharya.Rajan expanded payment modes to everyone by introducing payments through mobile phones. The UPI will soon revolutionize M2M payments in this country. the BHIM App gets into design mode.Rajan inspired a lot of western Indian-origin economists to come back and work for the country. His good friend Aravind Subramanian has been the CEA, Urijit Patel, Viral Acharya, and many more such private corporate stalwarts took lateral positions in the Government bodies. So, automatically, it would create resentment amongst the career-bureaucrats of those organizations who have worked for decades to reach that position. Jealousy starts creeping in.April 2015 - Niche Banks - Small Banks and Payment Banks - To create further penetration of the banking system, Rajan brought in new types of banks into the Indian system. He started giving licenses to private players to start banking practices in an innovative and safe way. This could have been a blockbuster pill to the ailing economy, and combined with the PM Jan Dhan Yojana, could have penetrated banking services to all the rural parts of the country.May 2015 - Strategic Debt Restructuring - In the last 12 months or so, banks started cleaning up their books and started identifying new NPAs. To help them with this issue, Rajan started the SDR on the lines of the CDR, but ensuring that the banks get equity in the companies’ exchange of loan. This ensured that the banks would have majority rights in the companies who have taken large bad loans. Another brilliant tactic, on paper.August 2015 - Modi Government asks Rajan about the SDR, NPA, BBB issue and again asks him to reduce the interest rates. Rajan says, not yet, monsoons have ended, and there is a flood of crops right now, so economic activity is in full swing. If he reduces the interest rates now, inflation will spiral up again.This pisses off Modi further. Enough is enough. Noone disobeys the Prime Minister, and especially not Modi. So, he decides to remove Rajan’s power of handling interest rates.The Monetary Policy Committee plan is ready. But Modi cannot implement it yet, as Rajan would just gain more sympathy. Till now only the RBI Governor had the power to change the interest rates. With the MPC in place, a team of 07 (03 Government nominees, 03 RBI nominees and RBI Governor) would take the decision together. RBI’s 70-year-old independence would finally be hampered by making the Government of India an integral part of the monetary policy.RBI’s independence starts to hamper.October 2015 - S4A - Scheme for Sustainable Structuring of Stressed Assets - To further help the NPA crisis, an innovate way to restructure only the sustainable part of the loans was thought of and was implemented.India’s ForEx Reserves under Raghuram Rajan almost doubles within a span of 03 years. (See chart - July 2013 to July 2017)The CPI inflation rate which touched 12% when Rajan took over, saw that it decreased to 4% by the time he left.The Tough Year - 2016Erosion of RBI’s IndependenceThe MPC Discussion - The Modi Government wanted 4 : 3 members (4 from the Government and 3 from RBI). Rajan said no. The discussion went forth and back for a few months and finally (3 : 3 with RBI Governor as a tie-breaker) was agreed upon.Modi extended Deputy Governor H R Khan’s term without even consulting with the RBI Governor. This was a severe breach of protocol.Modi announced that the Cabinet Secretary will head the interview panel to select RBI’s new Deputy Governors. Till now this was an internal matter, and the panel was always headed by the Governor. The Government started interfering in internal appointments matters also.Forced cooperation between the monetary and fiscal policy. The Government’s budget allocation and the RBI’s interest rate framework were made to align to the Finance Minister’s whims and fancies. Another breach of protocol.Attack from the media as Rajan made a political statement on Hindutva.Attack from Subramanian Swamy, where he said Rajan was not fit to be a Governor.Attack from internal RBI career-bureaucrats. It is difficult for anybody to put up a fight against an institution that does not want you to do your job, but still accuses you of not doing the job properly.It is ironical that the blame for growth is on Rajan when he actually did his prime job of keeping the foreign exchange and the currency in line.Feb 2016 - Developed CRILR - A large loan database to improve the mapping of loan distress and better access to information in this area.April 2016 - Rupee Stabilizes in the last 24 months at around 62 Rs. At mid 2013, as seen in the graph, the Rupee goes on a free-fall from 55 to 65, when Rajan takes over, and it still falls till 69, after which due to Rajan’s quick measures he brings the rupee back down to 62, and then keeps it hanging there continuously for the next 02 years till late 2015. After which the Rupee again starts weakening and starts touching 65.5. May 2016 - Modi talks about his dream with Rajan - The Demonetization. Rajan says no. He says it would create a lot of chaos and would not really remove the black money much.6. June 2016 - Modi decides not to give Rajan a second term. He does not announce anything though. He waits for 02 months for his tenure to get over silently.7. July 2016 - India is no more a “Fragile Five” economy announcement is made. It has been named one of the fastest-growing large economies of the world with a stable exchange rate, stable ForEx reserves and a stable inflation rate. Rajan gives a speech on this achievement. He is finally satisfied.7. August 2016 - Rajan decides to get back to academia.Sept 04, 2016 - Dr. Raghuram Rajan leaves RBI as its Governor.8. October 2016 - Modi installs the Monetary Policy Committee and takes the interest rates decision-making into his hands.9. November 08, 2016 - Two months after Raghuram Rajan leaves, Modi announces demonetization.Rajan didn’t step down.He was pushed out of RBI in one of the most unfortunate and horrifying decisions of the Modi administration.Unlike the past RBI governors who were given 5-year terms, Rajan was only given a 3-year term by Manmohan Singh as he didn't know how the public would perceive a foreign-studied RBI Governor, and the present government used that loophole to deny him a second term.While there were tensions even in the past amongst the RBI Governors and the Prime Ministers, they were quite less. The RBI governors have usually been mellowed bureaucrats who are honest and smart but will quickly back down from a conflict. They are typically old too, almost retired civil servants, chosen carefully to not have too much energy.Rajan, on the other hand, is among the youngest RBI Governors and is a man with lots of energy. He has an international reputation no other RBI Governor ever had.Within his 40s, he has seen some of the world’s best economics-related posts - including being the youngest Chief Economist of the IMF (International Monetary Fund).He doesn’t require a job.India required him.He was brought in as a desperate move in the last days of the Manmohan Singh government which had lost all its credibility due to the scams and needed something to restore India’s credibility in the financial and banking markets.Raghuram Rajan 's lethal combination of superior performance plus charisma has made him the most famous central banker ever in India. And easily, with his policies, one of the best.The problem lies in the system where the heads of key institutions are not expected to stay independent.The appointment of a bunch of yes-men to the most prestigious institutions, be it FTII, ICHR (Indian Council of Historical Research), NMML (Nehru Memorial Museum and Library), NIFT or even to the Censor Board shows a bad precedent for the country’s benefit.Every independent institution is losing its independence.And we need to realize that sooner or later.Rajan’s story is just one of many. A story where a strong, independent, intellectual man wanted to do some good for the country, but the system kicked him out.It is the country’s loss.

Neo-Riemannian music theory is an atonal triadic music theory that codifies maximally smooth voiceleading possibilities between triads. It is used to model chord progression in the so-called “second practice” of late 19th-ct. chromatic harmony (Liszt, Wagner, etc.). Loosely derived from Hugo Riemann’s tonal theories, it is a method for understanding late romantic harmony as a series of “operators” or “functions.” Two are familiar from basic tonal theory, but the third, the “leading tone exchange,” or Leittonwechsel, is a little more unusual:P (or parallel) = CEG - CEbGR (or relative) = CEG - CEAL (leading tone exchange) = CEG - BEGNote how each of these functions changes a single note in the chord, how each function changes a different scale degree (1, 3, or 5) and how that change is always by a single step (½ or 1 semitone).Using just these the operations, one can construct orderly progressions that move freely between implied key centers, or so freely that the only thing holding the music together is the smooth voiceleading.Try chaining the operators:RL = CEG - CEA - CFAPR = CEG - CEbG - BbEbGPL = CEG - CEbG - CEbAbPRL = CEG - CEbG - BbEbG - BbDGPLPL etc. = CEG - CEbG - CEbAb - CbEbAb/BD#G# - EG#B, etc.Note, finally how what in traditional tonal theory were “mixed” or “chromatic” progressions (I - bIII, I - bVI, I -III) etc.) are now explainable without resorting to imposing root progression on chromatic voiceleading patterns.Add an operators for tonic - dominant - subdominant moves (D), and you can model almost anything that happens in a Wagner opera or tone poem by Liszt or Rimsky Korsakoff.Hope this helps!

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.