The Impact of Activating Agents on Non-Enzymatic Nucleic Acid Extension Reactions.

Non-enzymatic template-directed primer extension is increasingly being studied for the production of RNA and DNA. These reactions benefit from producing RNA or DNA in an aqueous, protecting group free system, without the need for expensive enzymes. However, these primer extension reactions suffer from a lack of fidelity, low reaction rates, low overall yields, and short primer extension lengths. This review outlines a detailed mechanistic pathway for non-enzymatic template-directed primer extension and presents a review of the thermodynamic driving forces involved in entropic templating. Through the lens of entropic templating, the rate and fidelity of a reaction are shown to be intrinsically linked to the reactivity of the activating agent used. Thus, a strategy is discussed for the optimization of non-enzymatic template-directed primer extension, providing a path towards cost-effective in vitro synthesis of RNA and DNA.

Electrospinning Triboelectric Laminates: A Pathway for Scaling Energy Harvesters.

Herein, a new paradigm of triboelectric polymers-the triboelectric laminate-a volumetric material with electromechanical response comparable to the benchmark soft piezoelectric material polyvinylidene difluoride is reported. The electromechanical response in the triboelectric laminate arises from aligned dipoles, generated from the orientation of contact electrification in the laminates bulk volume. The dipoles form between sequential bilayers consisting of two different electrospun polymer fibers of different diameter. The loose interface between the fiber bilayers ensures friction and triboelectric charging between two polymers. The electric output from the electrospun triboelectric laminate increases with increasing density of the bilayers. This system design has clear benefits over other flexible devices for mechanical energy harvesting as it does not require any poling procedures, and the electromechanical response is stable over 24 h of continuous operation. Moreover, the electromechanically responsive electrospun laminate can be made from all types of polymers, thus providing ample room for further improvements or functionalities such as stretchability, biodegradability, or biocompatibility. The concept of a triboelectric laminate can be introduced into existing triboelectric nanogenerator form factors, to dramatically increase charge harvesting of a variety of devices.

Role of helicity in the nonenzymatic template-directed primer extension of DNA.

Complexing a DNA primer with an RNA template showed improved nonenzymatic template-directed primer extension, attributed to a shift in the DNA helicity from a B-type towards an A-type helix. A 2-fold (deoxyadenosine) and 4.5-fold (deoxycytidine) increase in conversion from initial DNA primer to a primer + 1 nucleotide product was observed.

Biofunctionality with a twist: the importance of molecular organisation, handedness and configuration in synthetic biomaterial design.

The building blocks of life - nucleotides, amino acids and saccharides - give rise to a large variety of components and make up the hierarchical structures found in Nature. Driven by chirality and non-covalent interactions, helical and highly organised structures are formed and the way in which they fold correlates with specific recognition and hence function. A great amount of effort is being put into mimicking these highly specialised biosystems as biomaterials for biomedical applications, ranging from drug discovery to regenerative medicine. However, as well as lacking the complexity found in Nature, their bio-activity is sometimes low and hierarchical ordering is missing or underdeveloped. Moreover, small differences in folding in natural biomolecules (e.g., caused by mutations) can have a catastrophic effect on the function they perform. In order to develop biomaterials that are more efficient in interacting with biomolecules, such as proteins, DNA and cells, we speculate that incorporating order and handedness into biomaterial design is necessary. In this review, we first focus on order and handedness found in Nature in peptides, nucleotides and saccharides, followed by selected examples of synthetic biomimetic systems based on these components that aim to capture some aspects of these ordered features. Computational simulations are very helpful in predicting atomic orientation and molecular organisation, and can provide invaluable information on how to further improve on biomaterial designs. In the last part of the review, a critical perspective is provided along with considerations that can be implemented in next-generation biomaterial designs.

A bright future for engineering piezoelectric 2D crystals.

The piezoelectric effect, mechanical-to-electrical and electrical-to-mechanical energy conversion, is highly beneficial for functional and responsive electronic devices. To fully exploit this property, miniaturization of piezoelectric materials is the subject of intense research. Indeed, select atomically thin 2D materials strongly exhibit the piezoelectric effect. The family of 2D crystals consists of over 7000 chemically distinct members that can be further manipulated in terms of strain, functionalization, elemental substitution (i.e. Janus 2D crystals), and defect engineering to induce a piezoelectric response. Additionally, most 2D crystals can stack with other similar or dissimilar 2D crystals to form a much greater number of complex 2D heterostructures whose properties are quite different to those of the individual constituents. The unprecedented flexibility in tailoring 2D crystal properties, coupled with their minimal thickness, make these emerging highly attractive for advanced piezoelectric applications that include pressure sensing, piezocatalysis, piezotronics, and energy harvesting. This review summarizes literature on piezoelectricity, particularly out-of-plane piezoelectricity, in the vast family of 2D materials as well as their heterostructures. It also describes methods to induce, enhance, and control the piezoelectric properties. The volume of data and role of machine learning in predicting piezoelectricity is discussed in detail, and a prospective outlook on the 2D piezoelectric field is provided.

A single peri-sciatic nerve administration of the adenosine 2A receptor agonist ATL313 produces long-lasting anti-allodynia and anti-inflammatory effects in male rats.

Neuropathic pain is a widespread problem which remains poorly managed by currently available therapeutics. Peripheral nerve injury and inflammation leads to changes at the nerve injury site, including activation of resident and recruited peripheral immune cells, that lead to neuronal central sensitization and pain amplification. The present series of studies tested the effects of peri-sciatic nerve delivery of single doses of adenosine 2A receptor (A2aR) agonists on pain and neuroinflammation. The data provide converging lines of evidence supportive that A2aR agonism at the site of peripheral nerve injury and inflammation is effective in suppressing ongoing neuropathic pain. After A2aR agonism resolved neuropathic pain, a return of pain enhancement (allodynia) was observed in response to peri-sciatic injection of H-89, which can inhibit protein kinase A, and by peri-sciatic injection of neutralizing antibody against the potent anti-inflammatory cytokine interleukin-10. A2aR agonist actions at the nerve injury site suppress neuroinflammation, as reflected by decreased release of interleukin-1ß and nitric oxide, as well as decreased sciatic expression of markers of monocytes/macrophages and inducible nitric oxide synthase. Taken together, the data are supportive that A2aR agonists, acting at the level of peripheral nerve injury, may be of therapeutic value in treating chronic pain of neuroinflammatory origin.

Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation.

Opioid use for pain management has dramatically increased, with little assessment of potential pathophysiological consequences for the primary pain condition. Here, a short course of morphine, starting 10 d after injury in male rats, paradoxically and remarkably doubled the duration of chronic constriction injury (CCI)-allodynia, months after morphine ceased. No such effect of opioids on neuropathic pain has previously been reported. Using pharmacologic and genetic approaches, we discovered that the initiation and maintenance of this multimonth prolongation of neuropathic pain was mediated by a previously unidentified mechanism for spinal cord and pain-namely, morphine-induced spinal NOD-like receptor protein 3 (NLRP3) inflammasomes and associated release of interleukin-1ß (IL-1ß). As spinal dorsal horn microglia expressed this signaling platform, these cells were selectively inhibited in vivo after transfection with a novel Designer Receptor Exclusively Activated by Designer Drugs (DREADD). Multiday treatment with the DREADD-specific ligand clozapine-N-oxide prevented and enduringly reversed morphine-induced persistent sensitization for weeks to months after cessation of clozapine-N-oxide. These data demonstrate both the critical importance of microglia and that maintenance of chronic pain created by early exposure to opioids can be disrupted, resetting pain to normal. These data also provide strong support for the recent "two-hit hypothesis" of microglial priming, leading to exaggerated reactivity after the second challenge, documented here in the context of nerve injury followed by morphine. This study predicts that prolonged pain is an unrealized and clinically concerning consequence of the abundant use of opioids in chronic pain.

Sustained reversal of central neuropathic pain induced by a single intrathecal injection of adenosine A2A receptor agonists.

Central neuropathic pain is a debilitating outcome of spinal cord injury (SCI) and current treatments to alleviate this pain condition are ineffective. A growing body of literature suggests that activating adenosine A2A receptors (A2ARs) decreases the production of proinflammatory cytokines and increases the production of anti-inflammatory cytokines. Here, the effect of administering intrathecal A2AR agonists on central neuropathic pain was measured using hindpaw mechanical allodynia in a rat model of SCI termed spinal neuropathic avulsion pain (SNAP). Other models of SCI cause extensive damage to the spinal cord, resulting in paralysis and health problems. SNAP rats with unilateral low thoracic (T13)/high lumbar (L1) dorsal root avulsion develop below-level bilateral allodynia, without concomitant motor or health problems. A single intrathecal injection of the A2AR agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido adenosine HCl (CGS21680) reversed SCI-induced allodynia for at least 6 weeks. The reversal is likely in part mediated by interleukin (IL)-10, as intrathecally administering neutralizing IL-10 antibodies 1 week after CGS21680 abolished the anti-allodynic effect of CGS21680. Dorsal spinal cord tissue from the ipsilateral site of SCI (T13/L1) was assayed 1 and 6 weeks after CGS21680 for IL-10, CD11b, and tumor necrosis factor (TNF) gene expression. CGS21680 treatment did not change IL-10 gene expression but did significantly decrease CD11b and TNF gene expression at both timepoints. A second A2AR agonist, 4-(3-(6-amino-9-(5-cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl)prop-2-ynyl)piperidine-1-carboxylic acid methyl ester (ATL313), was also able to significantly prevent and reverse SCI-induced allodynia for several weeks after a single intrathecal injection, providing converging lines of evidence of A2AR involvement. The enduring pain reversal after a single intrathecal injection of A2AR agonists suggests that A2AR agonists could be exciting new candidates for treating SCI-induced central neuropathic pain.

Laying Waste to Mercury: Inexpensive Sorbents Made from Sulfur and Recycled Cooking Oils.

Mercury pollution threatens the environment and human health across the globe. This neurotoxic substance is encountered in artisanal gold mining, coal combustion, oil and gas refining, waste incineration, chloralkali plant operation, metallurgy, and areas of agriculture in which mercury-rich fungicides are used. Thousands of tonnes of mercury are emitted annually through these activities. With the Minamata Convention on Mercury entering force this year, increasing regulation of mercury pollution is imminent. It is therefore critical to provide inexpensive and scalable mercury sorbents. The research herein addresses this need by introducing low-cost mercury sorbents made solely from sulfur and unsaturated cooking oils. A porous version of the polymer was prepared by simply synthesising the polymer in the presence of a sodium chloride porogen. The resulting material is a rubber that captures liquid mercury metal, mercury vapour, inorganic mercury bound to organic matter, and highly toxic alkylmercury compounds. Mercury removal from air, water and soil was demonstrated. Because sulfur is a by-product of petroleum refining and spent cooking oils from the food industry are suitable starting materials, these mercury-capturing polymers can be synthesised entirely from waste and supplied on multi-kilogram scales. This study is therefore an advance in waste valorisation and environmental chemistry.

A DNA Circuit for IsomiR Detection.

A synthetic DNA oligonucleotide has been programmed to function as a biological circuit to detect 5'-IsomiRs. The circuit consists of two integrated DNA switches. The first is "activated" when a DNA probe is enzymatically modified by a reverse transcriptase that incorporates nucleotides complementary to the 5'-region of a microRNA (miRNA). Addition of the correct number and sequence of nucleotides enables the probe to assemble into an asymmetric DNA hairpin. The reconfigured hairpin probe then primes an internal polymerisation reaction, resulting in the synthesis of a symmetrical DNA hairpin. This activates the second switch, which then initiates the amplification of reverse-transcribed miRNA through a continuous cycle of DNA nicking and polymerisation. The DNA circuit enables sensitive and rapid detection of femtomoles of a miRNA transcript under isothermal conditions.

Morphine amplifies mechanical allodynia via TLR4 in a rat model of spinal cord injury.

Central neuropathic pain (CNP) is a pervasive, debilitating problem that impacts thousands of people living with central nervous system disorders, including spinal cord injury (SCI). Current therapies for treating this type of pain are ineffective and often have dose-limiting side effects. Although opioids are one of the most commonly used CNP treatments, recent animal literature has indicated that administering opioids shortly after a traumatic injury can actually have deleterious effects on long-term health and recovery. In order to study the deleterious effects of administering morphine shortly after trauma, we employed our low thoracic (T13) dorsal root avulsion model (Spinal Neuropathic Avulsion Pain, SNAP). Administering a weeklong course of 10mg/kg/day morphine beginning 24h after SNAP resulted in amplified mechanical allodynia. Co-administering the non-opioid toll-like receptor 4 (TLR4) antagonist (+)-naltrexone throughout the morphine regimen prevented morphine-induced amplification of SNAP. Exploration of changes induced by early post-trauma morphine revealed that this elevated gene expression of TLR4, TNF, IL-1ß, and NLRP3, as well as IL-1ß protein at the site of spinal cord injury. These data suggest that a short course of morphine administered early after spinal trauma can exacerbate CNP in the long term. TLR4 initiates this phenomenon and, as such, may be potential therapeutic targets for preventing the deleterious effects of administering opioids after traumatic injury.

Approaches for the detection of harmful algal blooms using oligonucleotide interactions.

Blooms of microscopic algae in our waterways are becoming an increasingly important environmental concern. Many are sources of harmful biotoxins that can lead to death in humans, marine life and birds. Additionally, their biomass can cause damage to ecosystems such as oxygen depletion, displacement of species and habitat alteration. Globally, the number and frequency of harmful algal blooms has increased over the last few decades, and monitoring and detection strategies have become essential for managing these events. This review discusses developments in the use of oligonucleotide-based 'molecular probes' for the selective monitoring of algal cell numbers. Specifically, hybridisation techniques will be a focus.

Planar silver nanowire, carbon nanotube and PEDOT:PSS nanocomposite transparent electrodes.

Highly conductive, transparent and flexible planar electrodes were fabricated using interwoven silver nanowires and single-walled carbon nanotubes (AgNW:SWCNT) in a PEDOT:PSS matrix via an epoxy transfer method from a silicon template. The planar electrodes achieved a sheet resistance of 6.6 ± 0.0 Ω/□ and an average transmission of 86% between 400 and 800 nm. A high figure of merit of 367 Ω-1 is reported for the electrodes, which is much higher than that measured for indium tin oxide and reported for other AgNW composites. The AgNW:SWCNT:PEDOT:PSS electrode was used to fabricate low temperature (annealing free) devices demonstrating their potential to function with a range of organic semiconducting polymer:fullerene bulk heterojunction blend systems.

Sequence selective capture, release and analysis of DNA using a magnetic microbead-assisted toehold-mediated DNA strand displacement reaction.

This paper reports on the modification of magnetic beads with oligonucleotide capture probes with a specially designed pendant toehold (overhang) aimed specifically to capture double-stranded PCR products. After capture, the PCR products were selectively released from the magnetic beads by means of a toehold-mediated strand displacement reaction using short artificial oligonucleotide triggers and analysed using capillary electrophoresis. The approach was successfully shown on two genes widely used in human DNA genotyping, namely human c-fms (macrophage colony-stimulating factor) proto-oncogene for the CSF-1 receptor (CSF1PO) and amelogenin.

Understanding and Controlling Electrostatic Discharge in Triboelectric Nanogenerators.

Triboelectric nanogenerators (TENGs) have been widely used to harness various forms of mechanical energy for conversion to electrical energy. However, the contentious challenge in characterising TENGs is the lack of standard protocols for assessing mechanical-to-electrical energy conversion processes. Herein, macroscopic signal analysis is used to identify three key charging events within triboelectric signals: charge induction (CI), contact electrification (CE), and electrostatic discharge (ESD). By considering two phases of motion during contact-separation (approach and departure of the contact materials), CI arising from the motion of bound surface charge (varying electric field) between opposing contact materials is shown to dominate the measured displacement current signal, rather than the process of CE itself. Furthermore, the conventional signal (i. e., voltage, current, charge) interpretation of CE and CI during approach and departure phases is re-assessed, to indicate that the sudden spike of current often observed immediately prior to contact (or after separation) arises from polarity inverting electrostatic discharge (ESD). This aspect of the measured triboelectric effect, which is often ignored, is crucial for the design of TENGs and hence, techniques to enhance the understanding and control over the stochastic occurrence of ESDs is explored. The methods proposed for the deconvolution of the macroscopic signal components of TENGs, and mitigation of ESD occurrences, will allow for precise quantification of the associated charging events. The applications of this study will template the design and development of future super-TENGs with optimised energy conversion capabilities.

Undiagnosed Cancer Cases in the US During the First 10 Months of the COVID-19 Pandemic.

Importance: The COVID-19 pandemic disrupted the normal course of cancer screening and detection in the US. A nationwide analysis of the extent of this disruption using cancer registry data has not been conducted. Objective: To assess the observed and expected cancer rate trends for March through December 2020 using data from all 50 US states and the District of Columbia. Design, Settings, and Participants: This was a population-based cross-sectional analysis of cancer incidence trends using data on cases of invasive cancer diagnosis reported to the US Cancer Statistics from January 1, 2018, through December 31, 2020. Data analyses were performed from July 6 to 28, 2023. Exposure(s): Age, sex, race, urbanicity, and state-level response to the COVID-19 pandemic at the time of cancer diagnosis. Main Outcomes and Measures: Used time-series forecasting methods to calculate expected cancer incidence rates for March 1 through December 31, 2020, from prepandemic trends (January 2018-February 2020). Measured relative difference between observed and expected cancer incidence rates and numbers of potentially missed cancer cases. Results: This study included 1 297 874 cancer cases reported in the US from March 1 through December 31, 2020, with an age-adjusted incidence rate of 326.5 cases per 100 000 population. Of the observed cases, 657 743 (50.7%) occurred in male patients, 757 106 (58.3%) in persons 65 years or older, and 1 066 566 (82.2%) in White individuals. Observed rates of all-sites cancer incidence in the US were 28.6% (95% prediction interval [PI], 25.4%-31.7%) lower than expected during the height of the COVID-19 pandemic response (March-May 2020); 6.3% (95% PI, 3.8%-8.8%) lower in June to December 2020; and overall, 13.0% (95% PI, 11.2%-14.9%) lower during the first 10 months of the pandemic. These differences indicate that there were potentially 134 395 (95% PI, 112 544-156 680) undiagnosed cancers during that time frame. Prostate cancer accounted for the largest number of potentially missed cases (22 950), followed by female breast (16 870) and lung (16 333) cancers. Screenable cancers saw a total rate reduction of 13.9% (95% PI, 12.2%-15.6%) compared with the expected rate. The rate of female breast cancer showed evidence of recovery to previous trends after the first 3 months of the pandemic, but levels remained low for colorectal, cervical, and lung cancers. From March to May 2020, states with more restrictive COVID-19 responses had significantly greater disruptions, yet by December 2020, these differences were nonsignificant for all sites except lung, kidney, and pancreatic cancer. Conclusions and Relevance: This cross-sectional analysis of cancer incidence trends found a substantial disruption to cancer diagnoses in the US during the first 10 months of the COVID-19 pandemic. The overall and differential findings can be used to inform where the US health care system should be looking to make up ground in cancer screening and detection.

Trends in Oral Tongue Cancer Incidence in the US.

Importance: Oral tongue cancer (OTC) incidence has increased rapidly among young (<50 years) non-Hispanic White individuals in the US during the past 2 decades; however, it is unknown if age-associated trajectories have persisted. Objective: To examine US trends in OTC incidence and project future case burden. Design, Setting, and Participants: This cross-sectional analysis of OTC incidence trends used the US Cancer Statistics Public Use Database, which covers approximately 98% of the US population, and included individuals with an OTC diagnosis reported to US cancer registries between January 1, 2001, and December 31, 2019. Exposures: Sex, race and ethnicity, and age. Main Outcomes and Measures: Estimated average annual percentage change in OTC incidence from 2001 to 2019. Given the substantial incidence rate increases among non-Hispanic White individuals compared with those of racial and ethnic minority groups, subsequent analyses were restricted to non-Hispanic White individuals. Forecasted OTC incidence trends and case burden among non-Hispanic White individuals to 2034. Results: There were 58 661 new cases of OTC identified between 2001 and 2019. Male individuals (57.6%), non-Hispanic White individuals (83.7%), those aged 60 years or older (58.0%), and individuals with localized stage disease at diagnosis (62.7%) comprised most cases. OTC incidence increased across all age, sex, and racial and ethnic groups, with marked increases observed among non-Hispanic White individuals (2.9% per year; 95% CI, 2.2%-3.7%). Increases among female individuals aged 50 to 59 years were most notable and significantly outpaced increases among younger non-Hispanic White female individuals (4.8% per year [95% CI, 4.1%-5.4%] vs 3.3% per year [95% CI, 2.7%-3.8%]). While all non-Hispanic White birth cohorts from 1925 to 1980 saw sustained increases, rates stabilized among female individuals born after 1980. Should trends continue, the burden of new OTC cases among non-Hispanic White individuals in the US is projected to shift more toward older individuals (from 33.1% to 49.3% among individuals aged 70 years or older) and female individuals (86% case increase vs 62% among male individuals). Conclusions and Relevance: The results of this cross-sectional study suggest that the period of rapidly increasing OTC incidence among younger non-Hispanic White female individuals in the US is tempering and giving way to greater increases among older female individuals, suggesting a birth cohort effect may have been associated with previously observed trends. Recent increases among non-Hispanic White individuals 50 years or older of both sexes have matched or outpaced younger age groups. Continuing increases among older individuals, particularly female individuals, may be associated with a shift in the OTC patient profile over time.

COVID-19 and Rates of Cancer Diagnosis in the US.

Importance: US cancer diagnoses were substantially lower than expected during the COVID-19 pandemic in 2020. A national study on the extent to which rates recovered in 2021 has not yet been conducted. Objective: To examine observed vs expected cancer rate trends for January 2020 to December 2021. Design, Setting, and Participants: This cross-sectional, population-based study of cancer incidence trends used the Surveillance, Epidemiology, and End Results 22 (SEER-22) Registries Database, which covers 47.9% of the US population. Included individuals were those with an invasive cancer diagnosis reported to registries included in SEER-22 between January 1, 2000, and December 31, 2021. Exposures: Age, sex, race and ethnicity, urbanicity, and stage at diagnosis. Main Outcomes and Measures: Expected cancer incidence rates were measured for the COVID-19 pandemic years of 2020 and 2021 from prepandemic trends using ensemble forecasting methods. Relative difference between observed and expected cancer incidence rates and numbers of potentially missed cases were measured. Results: The SEER-22 registries reported 1 578 697 cancer cases in 2020 and 2021, including 798 765 among male individuals (50.6%) and 909 654 among persons aged 65 years or older (57.6%). Observed all-sites cancer incidence rates were lower than expected by 9.4% in 2020 (95% prediction interval [PI], 8.5%-10.5%), lower than expected by 2.7% in 2021 (95% PI, 1.4%-3.9%), and lower than expected by 6.0% across both years combined (95% PI, 5.1%-7.1%), resulting in 149 577 potentially undiagnosed cancer cases (95% PI, 126 059-176 970). Of the 4 screening-detected cancers, only female breast cancer showed significant recovery in 2021, exceeding expected rates by 2.5% (95% PI, 0.1%-4.8%), while significant reductions remained for lung cancer (9.1% lower than expected; 95% PI, 6.4%-13.2%) and cervical cancer (4.5% lower than expected; 95% PI, 0.4%-8.0%), particularly for early stage at diagnosis. Rates of all-sites cancer incidence returned to prepandemic trends in 2021 among female individuals, persons aged younger than 65 years, and persons of non-Hispanic Asian and Pacific Islander race and ethnicity. Conclusions and Relevance: This population-based cross-sectional study of US cancer incidence trends found that rates of diagnosis improved in 2021 but continued to be lower than expected, adding to the existing deficit of diagnosed cases from 2020. Particular attention should be directed at strategies to immediately increase cancer screenings to make up lost ground.

Toehold-mediated nonenzymatic DNA strand displacement as a platform for DNA genotyping.

Toehold-mediated DNA strand displacement provides unique advantages in the construction and manipulation of multidimensional DNA nanostructures as well as nucleic acid sequence analysis. We demonstrate a step change in the use of toehold-mediated DNA strand displacement reactions, where a double-stranded DNA duplex, containing a single-stranded toehold domain, enzymatically generated and then treated as a molecular target for analysis. The approach was successfully implemented for human DNA genotyping, such as gender identification where the amelogenin gene was used as a model target system, and detecting single nucleotide polymorphisms of human mitochondrial DNA. Kinetics of the strand displacement was monitored by the quenched Förster resonance energy transfer effect.

On-chip capacitively coupled contactless conductivity detection using "injected" metal electrodes.

We demonstrate the use of injected gallium electrodes for capacitively coupled contactless conductivity detection (C(4)D) within a microchip electrophoresis device. Evaluation of the electrodes for quantitative detection of electrophoretically separated lithium, sodium and potassium ions showed the system offers competitive detection limits of 6.1 × 10(-6) M, 6.7 × 10(-6) M and 8.5 × 10(-6) M, respectively. The fabrication process is fast, highly reproducible, and eliminates difficulties with electrode alignment. Using this approach C(4)D can be readily achieved in any microchip by simply adding extra 'electrode' channels to the microchip design.