In bi- and monolingual children, nonword repetition tasks (NWRTs) differentiate between typically developing (TD) and children with Developmental Language Disorder (DLD). Language specificity is a crucial factor in nonword construction especially for multilingual children. While language-specific nonwords seem less artificial than non-specific nonwords, the application of language-specific phonemes may be less suitable for bilingual children who are exposed to the target language less than monolingual peers. This study evaluates the concurrent and predictive value of a novel, computerized NWRT implemented in the MuLiMi web-platform and its potential in the discrimination of bilingual children with and without DLD, investigating the role of nonwords’ language specificity. Thirty-seven children  with at least one Italian-speaking parent, living and attending kindergartens in Germany were tested with the MuLiMi NWRT and German standardized language tests. Caregivers and kindergarten teachers filled in questionnaires. Fourteen of the children were re-tested after 8–12 months. The results suggest that the new test’s concurrent and discriminative validity are good. Analysis of variance revealed highly significant differences between children with and without (an objective risk of) phonological disorders and a significant interaction between nonword specificity and risk group. Significant correlations of initial scores with follow-up scores collected after 8–12 months were also found, as well as correlations with improvements in language abilities. In conclusion, although both language-specific and language-non-specific nonword repetition can support DLD risk identification in bilingual children, language-specific stimuli appear to be particularly sensitive indicators. This is interpreted as confirming DLD children’s reduced sensitivity to frequent, familiar characteristics of the linguistic stimuli. The test’s discriminative and concurrent validity showed to be robust to various potentially influencing factors like patterns of language exposure. The adequate identification of Developmental Language Disorder (DLD) in bilingual children has been described as a serious diagnostic challenge  with conNWRTs are considered increasingly relevant for the identification of DLD in bilingual children as children’s phonological processing abilities can be assessed directly and—at least compared to other tasks—relatively independently of their prior vocabulary knowledge that might be reduced compared to their monolingual peers due to variations in language input and exposure. Being less subject to the influence of language experience in the language of assessment , they woThe extant literature provides controversial evidence as to which type of NWs  yield the optimal discriminative power for differentiating between weak language performance due to underexposure and actual language impairment in bilingual children. No effects of language experience and dominance were found on the repetition performance of bilingual TD and DLD children with either Arabic, European-Portuguese, or Turkish as their L1 (family or heritage language) who used the French and the German versions of the LITMUS NWRT —not distThe number of conclusions to be drawn from previous research is limited, especially because findings on the relationships and interactions between language experience and repetition performance on language-specific NWs are mixed. In this study we compare NWs that take into account the characteristics of both languages and NWs that are relatively free (or freer) from such language-specific attributes in order to establish which NWs are more useful (discriminant) for the language assessment of bilingual children.Indeed, a prominent issue concerns the need or usefulness of administering NWRTs in the L1, in the L2 or in both languages for the diagnosis of DLD. This heterogeneity in findings may be explained by the great variability in methodological approaches that were applied in these studies, such as differences in the construction of the NWRTs, the characteristics of the NWs, the targeted language of assessment (the children’s L2 or L1) and the children’s age and patterns of language dominance.via questionnaires) has proven to be a sound method  language-specific (LS) items that take children’s language experience/dominance into account and (2) language-non-specific (LNS) items that are intended to assess children’s language abilities regardless of their language background. In order to avoid circular procedures, we will address diagnostic accuracy, taking into account information deriving from alternative tests of phonological ability and information collected through parental and kindergarten teachers’ questionnaires, including active use of language in addition to passive exposure. Finally, the goal of this study is to assess the validity of the “MultiMind Nonword Repetition Task,” which is part of a web-platform .The differences emerging between the groups of children with and without an objective risk of having DLD  based on pre-existing diagnoses and/or standardized language tests scores .The correlations between NWRT scores at T1 and follow-up (T2) scores .In order to identify the type or the types of NWs that have the best discriminative power we pose the following research questions (RQs):RQ1: Is MuLiMi NWRT repetition accuracy valid and reliable in the identification of DLD  as assessed by children’s risk status based on German standardized test scores? If yes, is performance in repeating LS items or LNS items more discriminant? And are accuracy scores on the (various types of) NWRT in accordance with parental questionnaires and kindergarten teachers’ subjective ratings?RQ2: Are there any advantages in using a bilingual NWRT over a monolingual one?RQ3: Is children’s language dominance correlated with children’s NW repetition accuracy and does language experience (dominance and exposure) influence improvement in NW repetition accuracy?RQ4: Does NW repetition accuracy at T1 predict improvement in overall language performance?M = 59.05, SD = 8.56) participated in this study. For the purpose of this study, two participants were excluded because of contradictory information in their parental questionnaires concerning whether or not they had an official diagnosis of DLD. At the time of testing, out of the 37 children, seven had already been diagnosed with DLD by German Speech and Language Therapists and were receiving treatment in Germany, 13 were considered TD, and 17 had neither been diagnosed nor treated for DLD but were identified as being at-risk for language impairment because they scored below a t-score of 40 in at least one of the standardized tests applied in this study (see section “German Standardized Tests”). Due to the phonological nature of the NWRT, a more specific type of “phonological risk” was identified for appropriate comparisons. This group comprised children who scored below a t-score of 35 in the German standardized NWRT (Mottier-test). According to this criterion, 10 children did, and 27 children did not, present with phonological risk. When participating in this study, all children were living in Germany. They all had at least one native Italian-speaking parent and were exposed to Italian—even though to varying degrees—on a daily basis. Participants with two Italian-speaking parents had been exposed to the German language for at least 2 years. While eight of the children were attending a German kindergarten, 31 were enrolled in a bilingual Italian-German kindergarten program. A subset of the children  participated in a follow-up study (T2) that occurred 8–14 months after the first evaluation (T1) repeating both standardized and experimental tests. Participant recruitment took place through either kindergartens or Speech and Language Therapy clinics. The study was approved by the institutes’ Ethical Committees and all parents signed informed consent according to the Declaration of Helsinki.Thirty-nine simultaneous or early-sequential bilingual Italian-German speaking children aged from 3;10 to 6;1 years  and an additional experimental protocol constituting a novel, web-based set of screening tasks for the assessment of risk of DLD . The Italian-German NWRT that is reported in this study is part of this experimental battery. Furthermore, caregivers were asked to complete a language background questionnaire providing information about their children’s language experience and exposure patterns and an extensive questionnaire on pregnancy, general and language development. Finally, kindergarten teachers were asked to complete a short survey on the children’s language skills across linguistic areas.n = 6; the other set is specific with respect to German ones, LS German, n = 6), recorded by expert native speakers of the respective language, and one set of LNS NWs . To make sure that the LS NWs complied with the phonotactic constraints of the respective language, phonemes and consonant clusters specific to each language were identified and used  or incorrect . As noted before, variations in accent or in the phonetic realization of single phonemes depending on language-specific features  were considered acceptable as long as the phoneme was clearly identifiable. The raw scores obtained in the MuLiMi NWRT reflect the number of NWs that were correctly repeated by each child  in the garbage can]. By contrast, an utterance such as “Weil ist traurig” with the verb in second position is considered level 3. A level is considered mastered if the child produces at least three utterances corresponding to that level throughout the entire test. As for Subject-verb-agreement, scores are calculated by first identifying all utterances that contain a subject and a verb and in a next step counting all the utterances with correct subject-verb agreement. Finally, the ratio between the number of occasions for subject-verb-agreement and the correctly realized instances is calculated. For instance, a common, correct response to the question elicitation “Was passiert hier?” [What is happening (in this picture)?] is “Die (Kinder) spielen Fußball.” [They are playing football.] By comparison an utterance such as “Spielen Fußball” is not included in the analysis as it is missing the subject. The maximum score is 1.0, children’s performance again is represented on a four-point scale.Children’s morpho-syntactic abilities in German were assessed using the elicited production task of the Linguistische Sprachstandserhebung Deutsch als Zweitsprache  was used to assess children’s language background. Depending on the families’ preference, the questionnaire was provided either in German or in Italian. The questionnaire included 34 questions concerning what language(s) children hear and speak on a daily basis. Children’s main caregivers were asked to use a seven-point scale using a combination of frequency adverbs and a percentage scale to estimate the proportion of their children’s Italian compared to German exposure in different contexts (one example for language input in the home: “What language(s) does the child hear from his/her mother” (1) only German; 100% German, 0% Italian, (2) predominantly German, hardly any Italian; 90% German, 10% Italian, (3) mostly German, sometimes Italian; 75% German, 25% Italian, (4) the same amount of German and Italian; 50% German, 50% Italian, (5) sometimes German, mostly Italian; 25% German, 75% Italian, (6) hardly any German, predominantly Italian; 10% German, 90% Italian, and (7) only Italian; 0% German, 100% Italian). Based on this information, an individual input  the child hears on a daily basis) and output  the child speaks on a daily basis) score were calculated for each language. The values obtained reflect the children’s current language experiences at the time of their participation in this study.A further questionnaire was completed by the child participant’s kindergarten teacher concerning the presence of difficulties in the domains of phonology, lexicon, morphosyntax and pragmatics. Each domain was judged according to a four-level scale .via the Mozilla Firefox web browser. For a subset of children (n = 14), follow-up (T2) data was collected between 8 and 14 months after the initial evaluation (T1). Parents and teachers’ questionnaires were filled individually on printed forms and returned to the researchers after a few days.Each child was tested individually in a quiet room by well-trained researchers either in one of the kindergartens or one of the Speech and Language Therapy clinics where they were recruited. In the few cases where this was not possible due to COVID-19 contact restrictions, children were tested in a quiet room in their homes. The test battery was administered in two separate sessions lasting between 40 and 50 min each. The NWRT was carried out using a Lenovo laptop, model YOGA 720-15IKB under the Windows 10 Pro operating system. The online screening platform MuLiMi was accessed Children were assigned to one of three groups  based on the information about a pre-existing diagnosis of DLD (DLD group) and whether they had obtained a t-score below 40 in at least one of the standardized tests applied in the study’s test protocol but without a pre-existing diagnosis of DLD (at-risk group). A further, more specific criterion for classifying children at-risk for phonological problems was applied dividing the group with respect to a cut-off of 35  for the t-score in the Mottier test .A variable expressing linguistic dominance was created based on parental reports, estimating the average number of hours each child is exposed to/actively speaks Italian during a regular week. Then, the number of hours was converted into a percentage in order to express the ratio between children’s weekly language input and output in Italian vs. German. A compound score for language dominance in which the input and output scores of both languages were merged was created based on the following equation:Based on the resulting score, children’s language dominance was assigned. The variable displaying dominance ranges from −1 (German dominant) to 1 . Children with a score of −1 to −0.16 were considered German dominant; −0.15 to 0.15 balanced; 0.16 to 1 Italian dominant.t-scores). Point-biserial correlations were computed for the association with dichotomous variables , whereas Spearman’s correlations were used in the case of three- or four-levels variables . In all other cases Pearson’s correlations were computed, under the condition that the variables’ distributions satisfied all requirements for such analyses. Nonparametric tests were used for the comparisons of small groups  or for non-continuous variables. Repeated-measures ANOVAS were performed on continuous, close-to-normally distributed variables (the scores obtained on various subsets of the NWRT) with Specificity (LS vs. LNS) and (after excluding LNS NWs) Language  as within-subject factors and Phonological risk (with vs. without) as a between-subjects factor. The effects of dominance as a covariate were also assessed. Nonverbal intelligence and age were added as covariates  whenever they had been found to correlate with the variables under exam.Data were analyzed by means of IBM SPSS Statistics v.26. The association between children’s NW repetition performance and their linguistic profile was assessed through partial correlation analyses, controlling for children’s language dominance, age (in months), and nonverbal intelligence . While the TD children leaned more towards the German-dominant end of the continuum compared to the DLD children who as a group were rather dominant in Italian, the children in the at-risk group represented a greater variety of experience patterns. Even though the difference in dominance patterns did not reach significance across the three groups , pairwise comparisons showed a significant difference in language dominance between the TD and the DLD group , whereas for the TD vs. at-risk group and the at-risk vs. DLD group no significant differences emerged (sp > 0.05).2χ(2) = 11.232, p = 0.004, with a mean rank of 26.46 for TD, 16.69 for at-risk and 10.50 for DLD children]. A Mann–Whitney-U-Test confirmed significant differences for TD vs. at-risk children  and TD vs. DLD children  but not for at-risk vs. DLD children (p > 0.05).In both the CPM and the Mottier-test, the TD children scored highest, followed by at-risk and then DLD children (see t(28) = 3.590, p = 0.001], at-risk vs. DLD children  and TD vs. DLD children .Performance (raw scores) in the Mottier-test was normally distributed in the sample. Running pairwise comparisons, significant differences emerged in the Mottier-test raw scores for TD vs. at-risk children . However, there was a significant interaction effect between NW Specificity and children’s Phonological risk status . Post-hoc tests showed that the NW repetition performance was significantly different for children with and without Phonological risk for both types of NWs . The repetition of LS NWs was significantly better than repetition of LNS NWs for the children without risk , whereas no significant difference emerged for the children with Phonological risk, who even performed (non-significantly) better with LNS than with LS NWs , but not for nonverbal intelligence and language dominance (sp > 0.05). No significant interaction between NW Specificity and children’s language dominance (p > 0.05) emerged either. Furthermore, the covariates did not show any significant interaction with Phonological risk.Furthermore, a repeated-measures ANOVA with NW Specificity (LS vs. LNS) as within-subject factors and Phonological risk (with vs. without) as a between-subjects factor and dominance, nonverbal intelligence and age as covariates was performed. There was no significant main effect for Specificity (M = 3.00 for both types) but not on number of phonemes  and this could have affected accuracy, Length in phonemes was set as a covariate in a repeated measures ANOVA with Phonological risk as a within-subject factor (subjects in this case were the NWs) and NW Specificity (LS and LNS) as a between-subject factor. The results showed that the effect of Phonological risk remained significant: F = 6.965, p = 0.017, η2 = 0.279 as well as the interaction between Phonological risk and Specificity: F = 8.954, p = 0.008, η2 = 0.332. Also the effect of Length almost reached significance, F = 4.372, p = 0.051, η2 = 0.195, but its interaction with Phonological risk did not, p = 0.327. When repeating the analysis with the three-level variable Clinical status as a within-subject factor , Specificity as a between-subject factor  and Length as covariate , the results clearly showed (see sp ≤ 0.001), the discriminative power  of LS turned out to be significantly higher (covarying for Length) than that of LNS for the comparisons between DLD and the other two groups, ps ≤ 0.036, and higher for LNS than LS for the comparison between TD and at-risk children (p = 0.025).Since LS and LNS nonwords were matched on number of syllables  = 8.028, p = 0.008] and a significant effect of Phonological risk status , but no significant interaction effect between Language and Phonological risk status (p > 0.05). Among the covariates, only age , but neither nonverbal intelligence, nor language dominance showed a significant effect on repetition performance. Moreover, a highly significant interaction emerged between age and language  = 19.385, p < 0.001), due to performance on LS-German NWs being rather stable at different ages, but performance on LS-Italian NWs increasing with age.A second repeated-measures ANOVA on LS items with Language  as within-subjects factor and Phonological risk (with vs. without) as between-subject factor, covarying for age, nonverbal intelligence, and language dominance, yielded a significant main effect of Language [ps ≤ 0.001). A cut-off of 12.5 would allow for a sensitivity of 0.800 and a specificity of 0.815 in identifying phonological risk, and a sensitivity of 0.857 and a specificity of 0.767 in identifying DLD. When comparing LS and LNS NWs according to their sensitivity and specificity in identifying children with phonological risk and with DLD, respectively, it can be seen that LS produce better ROC curves (AUC = 0.933 and 0.931) than LNS NWs . Use of LS NWs alone would allow reaching a specificity (with unchanged sensitivity) of 0.900 for DLD identification and 0.963 for phonological risk identification . All ROC curves are presented in In order to confirm the discriminative power of the NWRT, an exploratory analysis of diagnostic accuracy  was performed with respect to the identification of the presence of phonological risk , as well as of DLD (as opposed to TD) in the clinical status classification, in spite of the small sample size. The ROC curves produced by the total NWRT score were very encouraging, with AUC (area under the curve) values as high as 0.917 and 0.898, respectively  and the compound scores LS-total  and LNS-total  and with the NWRT total score . These results remained stable when controlling for age and nonverbal intelligence. Children’s scores obtained in the Mottier-test correlated higher  than with the repetition of LS-German NWs. The comparison of correlation coefficients for LS total and LNS total with Mottier raw scores did not yield fully significant results . For the two categorical variables verb placement and subject-verb agreement based on the LiSe-DaZ German standardized test, Spearman correlations revealed significant associations with NW repetition performance across subcategories and in the total score  except for the association between verb placement in the LiSe-DaZ and LNS-total . All the NWRT scales were also significantly associated with raw scores in the PPVT German standardized vocabulary test . This pattern was substantially maintained when controlling for age and nonverbal intelligence . Repetition performance across all NWRT scales further correlated with the German CLT compound (noun and verb comprehension) score , whereas the Italian CLT compound score was significantly associated only with repetition performance of LS-Italian  and LNS-total  but not with LS-German  nonwords, and thus not significantly associated with the NWRT total score. This pattern of results remained substantially stable when controlling for age and language dominance, but when adding nonverbal intelligence as a control variable no significant associations were found with the CLT Italian compound score .Performance across all NWRT scales was significantly associated with several standardized measures. Most importantly, the raw scores in the Mottier-test were significantly associated with the percentage of correctly repeated LS NWs (n = 36) or output (n = 35) in the two languages correlate with any of the NWRT scales .For one of the children conflicting information between the parental questionnaire and teachers’ reports emerged regarding his/her amount of Italian output. This participant was thus excluded from the analyses on the Italian output variable. No significant correlations emerged between children’s language dominance scores and their performance on any of the subcategories of NWs, nor did children’s language input . Particularly teachers’ judgment of children’s productive phonology skills correlated significantly with children’s NWRT scores across all scales  except for LS German .Teachers’ global evaluation of children’s language performance correlated significantly with children’s clinical/risk status , risk score  and family global input score . Furthermore, children’s performance in all NWRT scales was significantly associated with the scores in the parental questionnaire with the exception of the QUIR-DC FIGS (see t-scores).One of the children had to be excluded from the analysis concerning parental questionnaires since her/his parents never returned the QUIR-DC questionnaire. Children’s clinical/risk status was significantly associated with the responses of their parents in the QUIR-DC general score  and for LNS-total . Language dominance was not significantly associated with improvement in NWRT scores from T1 to T2 . However, an interesting, negative association was found between the amount of Italian output at T1 and the improvement of LS-German scores  as assessed by children’s risk status based on German standardized test scores? If yes, is performance in repeating LS items or LNS items more discriminant? And are accuracy scores on the (various types of) NWRT in accordance with parental questionnaires and kindergarten teachers’ subjective ratings?t-scores). The same results emerge from the correlations between the children’s scores on the NWRT and their position within the classifications expressing clinical status or phonological risk. They further highlight that LS NWs are more discriminant than LNS NWs, especially when the goal is to discriminate between TD and both at-risk and DLD children, or children with phonological risk. ROC curves  confirm that the NWRT, and especially LS NWs, may allow the identification of children with either phonological risk or DLD with very good sensitivity and specificity figures.Reliability of the MuLiMi NWRT was assessed both in terms of inter-rater reliability and of internal consistency. Both indexes were found to be satisfactory. For what concerns validity, children’s performance across all NWRT scales was significantly associated with a wide range of standardized test results. The significant correlations between children’s performance on the MuLiMi nonwords and their scores on further standardized language tests indicate that the task can support the identification of bilingual children’s risk of DLD, irrespective of children’s nonverbal intelligence  is positively associated with most language tests  influence improvement in NW repetition accuracy?Similar to what has been found in previous studies e.g., , TD chilEven though dominance differed significantly between the TD and DLD group , no significant association between children’s language dominance and their repetition performance in any of the nonword subcategories was found. Moreover, a measure of German input quality in children’s homes collected through parents’ questionnaires did not correlate significantly with children’s nonword performance in any of the scales cf. . NonetheThe absence of any influence of language experience on nonword repetition may also suggest that the bilingual children included in this study had already acquired sufficient experience with both of the languages to perform equally well (or badly) on German and Italian language-specific nonwords cf.  and thusRQ4: Does NW repetition accuracy at T1 predict improvement in overall language performance?Overall, the significant associations between nonword repetition performance at T1 and T2 across subcategories suggests that the MuLiMi NWRT scores are sufficiently stable across time. Since several months passed between T1 and T2 and since some of the children received Speech and Language Therapy treatment during this period, these correlations cannot be considered as proper measures of test–retest reliability.Notably, significant associations of children’s nonword repetition accuracy at T1 and their improvement of NWRT scores were found for LNS nonwords but not LS nonword repetition performance. Since performance on LNS at T1 was generally lower than performance on LS nonwords, it is likely that this difference indicates a larger space for improvement for the former than for the latter. Nonetheless, a negative correlation of LNS nonwords at T1 with improvement on the same measure was found. Also, we found greater discriminative power for LS compared to LNS items with respect to phonological risk status. This could indicate that a low performance on LNS items (compared to low performance on LS items) is less likely to reflect a specific impairment of phonological skills. In other terms, there is a greater probability for the repetition of LNS items to improve with time, possibly regardless of clinical intervention.The main limitation of the study, due to the difficulty of finding children with DLD belonging to this particular language combination and to limited access to kindergartens and clinical structures during COVID-19-related restrictions, is a relatively small sample size and unequal number of TD children and children with (risk of) DLD. Moreover, the children included in this study do not sufficiently represent the great heterogeneity of language experience scenarios in the bilingual population. Participants were predominantly early sequential or simultaneous bilinguals who most likely had already had sufficient exposure in both languages to perform equally well on LS-German and LS-Italian nonwords. This might be due to the recruitment method with the help of  bilingual kindergartens where children receive dual language input. It was therefore not possible to examine how later onset of exposure and acquisition of a second language would influence performance on LS vs. LNS nonwords. The fact that all DLD children were Italian-dominant is also remarkable. This might be a random effect due to small sample size for the DLD group, but it may also suggest that insufficient language exposure to the societal language can be a possible confound in diagnosis, or that it could interact with neurobiological risk factors making the language impairment in the L2 more evident  and thus enhancing the probability of early diagnosis and treatment. Other possible explanations may call socio-cultural factors into play, the analysis of which is beyond the scope of the present study. These issues could be addressed in future studies where a greater heterogeneity of  acquisition patterns is represented in the sample, including simultaneous, early as well as later sequential bilinguals. It would also be interesting to include monolingual participants in order to examine how repetition is affected by the presentation of nonwords whose characteristics go against the phonotactic constraints of their native language.Furthermore, even if whole word scoring is sufficient to discriminate DLD from TD children, in how far in-depth analyses on syllable- & phoneme-level as well as error analyses could provide additional, useful information will need to be addressed in future studies.A more general methodological issue and characteristic of most studies on DLD in bilingual population is the circularity between classification and verification. In fact, the classification of children into risk groups is largely based on the results of standard test procedures whose informative value and application with multilingual children is limited. This limitation applies not only to the test procedures with monolingual norms  but also to tests with norms for the bilingual population, which (like the LiSe-DaZ) normally refer to a large variety of L1s and to certain bilingual acquisition scenarios only. In this perspective, it would be useful if future studies could incorporate phonological and articulatory tests in both the L1 and the L2.Finally, the effect of “neutral” intonation in the presentation of LNS nonwords needs to be investigated in more detail since this type of presentation while avoiding language-specific prosodic features on the one hand, on the other hand makes the stimuli sound rather unnatural, a characteristic that might influence repetition performance.Summarizing the results of the study with respect to the research questions that were initially raised, it can be concluded that children’s repetition accuracy in the MuLiMi NWRT differs according to their risk status , confirming the task’s discriminative validity, with a stronger capacity of LS than LNS nonword repetition accuracy to discriminate between children with and without a phonological risk (RQ1). Furthermore, MuLiMi nonword repetition performance is associated with German standardized test scores, confirming the task’s concurrent validity (RQ1). Both teachers’ subjective ratings of children’s language performance and parental reports about children’s language development are largely associated with NW repetition accuracy (RQ1). For bilingual children, the bilingual MuLiMi NWRT is more informative than the monolingual Mottier-test (RQ2). Neither nonword specificity nor children’s language dominance had an impact on NWRT (RQ3), but improvement in NW repetition performance from T1 to T2 did show an effect of language use (RQ4). Preliminarily investigating the MuLiMi NWRT’s predictive validity, children’s repetition performance at T1 correlated significantly with repetition performance at T2 (pointing to stability of the measure) and with improvement (RQ4) which for certain nonword subscales was significantly associated with children’s language use (RQ3).Thus, in line with previous research e.g., , a combiDue to the independence of repetition performance from language dominance, a combination of LS and LNS items provides a satisfactory solution for the identification of language disorders despite the great variety of language experience patterns present in the bilingual population. The present results also suggest that the task is sufficiently robust with respect to the possible impact of nonverbal intelligence and age (within the kindergarten and preschool age range) variations, beyond different language dominance patterns.For clinical purposes of DLD risk identification and in order to plan and design appropriate intervention strategies, LS nonword repetition performance is the most suitable measure. Repetition of LNS nonwords seems to be more informative with respect to possible improvement in performance, probably due to less specific, more exposure-related impairments. It is thus suggested that a comprehensive assessment should comprise both LS as well as LNS items: the reduction of the items to a relatively small amount of nonwords very carefully selected from the initial list so as to maximize item distinctiveness while preserving validity and reliability allows for relatively fast but highly reliable and informative testing outcomes.The raw data supporting the conclusions of this article are available on the Zenodo repository, DOI: 10.5281/zenodo.6519135. Personal data concerning participant children will be made available upon request to the corresponding author. Access will be granted to named individuals in accordance with ethical procedures upon completion of a formal data sharing and collaboration agreement, and approval by the ethics committee and legal authority.The studies involving human participants were reviewed and approved by Ethics Committee of the Scientific Institute Eugenio Medea, scientific section of the association “La Nostra Famiglia,” via Don Luigi Monza 20, Bosisio Parini (LC) 23842, Italy on 17 June 2019 (no. 43/19); Ethics Committee of the Catholic University Eichstätt-Ingolstadt, Ostenstraße 26, 85072 Eichstätt, Germany, on 21 January 2020 (no. 009-19). Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.ME and TB contributed to the conception of the study, definition of the experimental materials for German and Italian, performed data collection, processing and analyses for the study, and contributed to the interpretation of results. ML took care of the conception and definition of the experimental design, assisted in the definition of experimental materials, participated in the interpretation of results, performed statistical analyses, and supervised the whole study. All authors contributed to writing the manuscript, read, and approved the submitted version.This project has received funding from the European Union’s Horizon 2020 program for research and innovation under the Marie Skłodowska Curie Grant Agreement No. 765556  and by the Italian Ministry of Health, Grant RC2021 to ML. The APC was funded by the IRCCS E. Medea, Bosisio Parini, Italy.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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The study of neurotransmitters and stress hormones allowsthe determinationof indicators of the current stress load in the body. These speciesalso create a proper strategy of stress protection. Nowadays, stressis a general factor that affects the population, and it may causea wide range of serious disorders. Abnormalities in the level of neurohormones,caused by chronic psychological stress, can occur in, for instance,corporate employees, health care workers, shift workers, policemen,or firefighters. Here we present a new nanomaterials-based sensorstechnology development for the determination of neurohormones. Wefocus on fluorescent sensors/biosensors that utilize nanomaterials,such as quantum dots or carbon nanomaterials. Nanomaterials, owingto their diversity in size and shape, have been attracting increasingattention in sensing or bioimaging. They possess unique properties,such as fluorescent, electronic, or photoluminescent features. Inthis Review, we summarize new trends in adopting nanomaterials forapplications in fluorescent sensors for neurohormone monitoring. Neurohormones, which are themain regulators of the stress response, are physiologically activesubstances produced by the nervous system.8 As very often the first symptoms of stress-induced diseases  areunderestimated, the development of biosensors that would enable themonitoring of parameters related to exposure to stressful conditionsis extremely important. Knowledge about the level of neurohormonesis an essential factor in modern medicine; however, there is no availablemethod for accurate, sensitive, fast, and direct analysis that wouldallow monitoring the concentration of these species.Nowadays, stress is ageneral factor affecting the population,and it may cause a wide range of serious disorders. Chronic stresscan have a large pathophysiological impact on neuroendocrine12 The employment of nanomaterials (NMs) in biosensors permits theuse of many new signal transduction technologies in their manufacturing.Nanomaterials, e.g., nanoparticles (NPs), nanotubes, nanofibers (NFs),nanorods, or quantum dots (QDs), have large possible application inthe construction of biosensors.13 Thesematerials possess a wide range of different properties, and thereforethey are included in functional materials , which can be bound to the biological molecules and usedin biosensors to determine or amplify different signals.14 The unique optical properties of NMs, especiallyquantum dots, make the NMs attractive fluorophores that can be usedboth in vitro and in vivo in various biological studies, where traditionalfluorescent labels based on organic molecules do not provide long-termstability or high enough intensity or where a simultaneous detectionof many signals is needed.15 In sensors,the signal detection is based on the registering of a change in oneof the physical properties  of sensing materials induced by the interaction withthe analyte. The main advantages of using the nanoparticles, e.g.,changing their optical properties, such as emission color, intensity,polarization, or emission kinetics, can be used as the principle inoptical sensors systems.13 The use of carbon-and cadmium-based nanomaterials for the construction of sensors requiresadjusting their properties  adequately to the needs thatarise. Moreover, to obtain specificity of NMs in their sensing action,the surface modification, called functionalization, must be appliedfirst.17 There are several methods for detectingan analyte with NPs, e.g., emission quenching from NPs, increase inNPs’ emission due to passivation of the NPs’ surfaceby the analyte, and nonradiative Förster resonance energy transfer(FRET).18 Nanostructured materials withgreat potential for the easy identification of individual chemicalcompounds with minimized sample volumes and their treatment are particularlypromising in the process of biosensors development. Such materialsinclude, e.g., carbon nanotubes (CNTs), graphene, and quantum dots,which very often are combined in optical sensor/biosensor detectionsystems. Optical biosensors represent a common type of biosensors,where the detection is based on the interaction of the optical fieldwith a biorecognition element.19 Thesetools are stable owing to their resistance to radio interference andother electromagnetic waves. It is worth mentioning that they usuallyshow high sensitivity, while simultaneously measuring without causingcontamination of the sample with the reaction product.20The evolutionof biosensors was driven by the need for faster andmore versatile analytical methods for application in important areasincluding clinical diagnostics, food analysis, environmental monitoring,and industry analysis in complex sample matrices , with minimal sample pretreatment. Nowadays, an increasing interestin combining nanotechnology with biosensor construction is observed.Here, an overview of the recent developmentsin the field of nanomaterials-basedoptical sensors and biosensors that showed suitable detection limitsto determine neurohormones in biological fluids is presented 1.222 The most commonly useddetection methods in optical sensors are based on fluorescence andabsorption phenomena.Many various detection methods  can be utilized in the design of sensors and biosensors.One of the most accurate and at the same time versatile methods isthe optical one. The operating principle of sensors using this methodis based on several optical phenomena which can be divided into twogroups–luminescent  and nonluminescent .2.123 The quantity describing the ability of a substance to absorblight of a specific wavelength is absorbance. According to the well-knownLambert–Beer’s law, it is possible to determine analyteconcentration based on absorbance measurements. The absorbance magnitude(A) can be expressed as the logarithm of the ratioof the incident light intensity (I0) andthe light transmitted to the detector (I).25–1 M–1), l is the optical path length (in cm), and c is the concentration of the analyte (in M).Absorption is a phenomenonin which the photon energy of incident electromagnetic radiation isabsorbed partially or in total by the examined analyte. As a result,the valence electrons of the atom are excited to higher energy levels,and subsequently absorbed energy may be transformed into heat or emittedas other electromagnetic radiation .26 Its length may be extended by incorporating,e.g., optical mirrors.27In absorptionspectroscopy, a light source of a given wavelength or selected spectrumis positioned opposite to a sensor. The key element in absorbancemeasurements is the selection of an optical path length that willprovide an adequate signal-to-noise ratio. Depending on the designof the sensor and the nature of the performed measurements, the opticalpath may follow either perpendicular or parallel to the fluidic channel.2.228 Thisradiation has a longer wavelength than the excitation one. The photonenergy (E) is expressed as the product of Planck’sconstant (h) and the frequency of the wave (ν),which can be presented as the ratio of the speed of light (c) and the wavelength (λ).The phenomenon in whichelectromagnetic radiation is emitted as a result of exposure to radiationof a different, shorter wavelength is called fluorescence. A fluorophoreor a fluorescent dye absorbs the energy of incident photons and isexcited to a higher energy level as a result of radiation-free transitions.Over a short period of time, called the excited state lifetime, avibrational relaxation of the fluorophore occurs. As a result, itsenergy is decreased, and eventually the electrons return to theirvalence band radiating photons.ex) and emission (λem) radiation is known as the Stokes shift and can range from 10 to150 nm. The fluorophore can be excited numerous times, and the fluorescentemission can be obtained repeatedly before it is no longer able tofluoresce. This process is also known as photobleaching.29 The efficiency of the fluorescence process isdetermined by the quantum yield of the fluorophore and is a ratioof the emitted to the absorbed number of photons.23 Most commonly, fluorescence measurements are performedutilizing radiation in the range from 250 to 750 nm.28 Selected common fluorescent labels along with their excitationand emission wavelengths are presented in 30The wavelength difference between theexcitation , and the photodetector that recordsthe light intensity and produces a measurable value.Novel optical-basedbiosensors utilize relatively small-sized lightsources that are based on semiconductor compounds (mainly from theIII-V and II-VI groups). The most popular light sources are semiconductorlasers, superluminescence diodes, and light-emitting diodes (LEDs).Light emissions for different semiconductor compounds that are usedfor the fabrication of light sources are presented in 38 The base materialsused to fabricate these devices are, e.g., silicon, germanium, indiumgallium arsenide, and lead sulfide. The wavelength ranges of exemplarysemiconductors and semiconductor compounds that are used for photodetectorsare presented in As a photodetector, mainly a photodiode, phototransistor,or charge-coupleddevice (CCD) is used. In addition, CMOS-type  detectors  and mini-spectrometers have increasingly been used in sensingapplications in recent years.As can be seen in In fluorescence spectroscopy, we observe the lightemitted by thetested object; therefore, the light source should be positioned perpendicularto the photodetector or be separated by a set of mirrors and filters.Possible configurations of the light source with respect to the photodetectorare shown in 4amaterial with any external dimension in the nanoscale (length rangeapproximately from 1 to 100 nm) or having internal structure or surfacestructure in the nanoscale”.40 Nanomaterials possess specific chemical, physical, and biologicalproperties.41 They are characterized bylarge surface area to volume ratio, ease of functionalization, porosity,and therefore high loading capacity, and in some cases unique opticalproperties, thanks to which they find applications in the constructionof optical sensors and biosensors, enabling their miniaturizationand improving their performance, limit of detection, and responsetime.43 Functionalization of nanomaterials may additionallyenhance the binding affinity toward the target, improve the stabilityin aqueous solutions, and give desired properties.44Nanomaterials are promising structures for applicationsin sensors.A nanomaterial, as defined by ISO standards, is “45A variety of nanomaterials have found applicationin the constructionof fluorescent sensors 3. The ch4.1hollow nanofibercomposed of carbon”.79 The tubularshape of CNTs comes from curled-up graphene sheets. Depending on thenumber of cylindrical graphene layers, CNTs can be classified intosingle-walled CNTs or multiwalled CNTs . The former attractedspecial attention in sensing and biosensing research. SWCNTs can havea zigzag, armchair, or chiral structure, which are then classifiedas semiconducting, metallic, or semimetallic, respectively. The mostadvantageous properties of these one-dimensional structures include,apart from large surface area and mechanical properties, electronic,electrochemical, and photophysical properties, electrochemical stability,and thermal and electrical conductivity. In comparison to other methodsused in biosensors, such as antigen–antibody interactions,CNTs present a stable, low-cost, reproducible material that does notrequire living organisms for production. In addition, their nanoscalesize may lead to precise targeting of the molecules.82According to ISOStandards, a carbon nanotube is a “84The physical construction of SWCNTs defines their opticalproperties. Because of their nanoscale size (ranging from 0.7 to 3nm in diameter), they are subject to the quantum confinement effect,which leads to near-infrared fluorescence in the range of 900–1600nm. This fluorescence is sensitive to its local environment and dependson several factors, such as the diameter and chiral vectors of theCNT, the local dielectric environment, charge transfer, and the presenceof fluorophores or Coulombic interactions. SWCNTs exhibit strong resonanceRaman scattering and possess a broad absorption spectrum, which makesit possible to use them as quenchers for different fluorophores.84 Functionalization creates an organic phase, called a corona, onthe surface of CNTs. A perfect coating should be nontoxic, biocompatible,and stable and possess specific functional groups that allow furthermodification; for example, modification with oxygenated moieties mayleave carboxylate groups on the surface of CNTs. These groups improvewater solubility and can be used for further bioconjugation. Dispersionin aqueous solutions is also possible by using surfactants, such assodium dodecyl sulfate, or soluble molecules, including proteins,nucleic acids, and polysaccharides. In the case of covalent modification,oxidation and cycloaddition are often used.84Initially, SWCNTs are hydrophobic and tend to aggregate. Properlyselected surface modification, covalent or noncovalent, can make themnot only hydrophilic but also biocompatible, adapting them for applicationsin sensors and biosensors. It also tunes the fluorescence propertiesof SWCNTs. Properties, including high photostability, lack of photobleachingand lack of blinking, various chiralities, and biomolecule comparabledimensions, make SWCNTs a good material for sensing applications.83 or glucose levels85), proteins,81 metals,86 or neurotransmitters.67SWCNTs have been applied in opticalsensors for the detection of,e.g., biomarkers  are another promising carbon-basedNM. CDs are nearly spherical, fluorescent carbon materials with onedimension less than 10 nm. Their synthesis is cheap and biofriendly,and they are biocompatible, soluble, and resistant to photobleaching.Because of abundant functional groups, such as hydroxyl, carboxyl,and amine, they can be easily functionalized. They possess high fluorescencestability and strong absorption in the ultraviolet region, expandableto the visible region, they do not blink, and the excitation and emissionwavelengths are adjustable. CDs-based sensors have been developedfor the detection of, for example, metal ions, pesticides, and biomoleculessuch as nucleic acids or for use in food safety.94 In addition, because of their fluorescent properties, granted bythe radiative recombination of electron–hole pairs, they canserve as fluorescent labels or quenchers. The nanoscale allows forthe quantum effects, exciton confinement, and quantum confinementleading to a band gap and edge effects, which lead to optical andelectrical properties unobtainable in classic quantum dots. GQDs canbe easily functionalized, as a large number of sites for potentialmodification is provided by their structure. Functionalization canbe carried out using organic molecules and biomolecules, such as proteins,amines, nucleic acids, or antibodies, or using nanomaterials, creatinghybrid NMs.95Graphenequantum dots (GQDs) are zero-dimensional, fluorescent nanomaterialsconsisting of one or few layers of graphene. As a carbon-based material,GQDs present excellent biocompatibility and low to no toxicity, aswell as good solubility in various solvents, including aqueous solutions.They possess properties characteristic of both graphene and quantumdots. They exhibit good mechanical, electrical, thermal, and opticalproperties, as well as large surface area, chemical inertness, highfluorescence activity, and photoluminescence stability.93 Optical sensors basedon GQDs have been used to detect, for instance, metal ions (such ascopper(II),94 iron(III),96 and mercury(II)97) or organiccompounds .There are two main categories of synthesisof GQDs: the top-downapproach and the bottom-up approach. The first one is a simpler methodthat involves a fragmentation of carbon materials, such as grapheneoxide, CNTs, graphite, or carbon fibers, through, e.g., chemical orelectrochemical oxidation. However, control of the size and morphologyof created GQDs is not possible. The second approach involves severalchemical reactions from smaller precursors, such as citric acid orpolycyclic aromatic hydrocarbon, to create GQDs, e.g., hydrothermaltreatment and chemical vapor deposition. Examples of methods for thesynthesis of GQDs are presented in 4.3crystalline nanoparticles that exhibit size-dependentproperties due to quantum confinement effects on the electronic states”.100 They are semiconducting,inorganic, fluorescent nanocrystals, usually synthesized from elementsof groups II-VI or III-V. Their size is limited by the exciton Bohrradius of the material and usually ranges from 1 to 10 nm. Specialfocus is placed on QDs with the size of 2–6 nm, as they resemblebiomolecules.104 Optical properties, which can be tuned by controlling the size ofQDs, are characterized by narrow emission spectra, broad excitationspectra, long fluorescence decay lifetime, high quantum yield, andlack of photobleaching.105 QDs can have a core–shell-like structure, where the coreis surrounded by another layer, usually made of a different compound.The shell protects the core from photo-oxidation and improves thequantum yield.106Quantum dots are definedas “105 Green synthesis has also been described, where toxic compoundsare replaced with environmentally friendly substances and lower temperaturescan be used.107One of the mostpopular methods of synthesis of QDs is the hot-injection method. Inthis technique, precursors of the core compounds are injected intoa hot surfactant, starting the process of nucleation. Then the temperatureis lowered to let the crystals grow, and the process is stopped whenthe nanocrystals reach the desired size. The surfactant moleculesbecome the ligands on the surface of the NPs.108 The ligands on the surface of QDs affect theirsize, shape, optical and physicochemical properties, colloidal stability,and dispersion in polar and nonpolar environments, as well as furtherbioconjugations.109 The simplest modification methodis ligand exchange, where hydrophobic surface molecules are replacedwith molecules with two functional groups, hydrophobic for the surfacebinding  and hydrophilic  for water solubility. Replacement ligands mayinclude, e.g., 3-mercaptopropionic acid or d-penicillamine.112 Silanization is the synthesis of a siloxane layer around a singlequantum dot, and amphiphilic molecules can create a cross-linked polymerlayer around a single QD.110The organometallicsynthesis of QDs causes the requirement of surfacemodification in order to obtain hydrophilic QDs that could be furtherfunctionalized and applied in biomedicine and sensing. Most commonlyused techniques include ligand exchange, silanization, and amphiphiliccoating 5.108 The13 for instance,in the detection of metal ions,113 pesticides114 or toxins,115 sugars,116 microorganisms,117 and biomolecules, such as proteins,118 nucleic acids,119 neurotransmitters,120 or vitamins.121Because of their unique optical properties, QDshave found applicationin many optical sensors,4.4123Gold nanoparticles(AuNPs), also known as colloidal gold, are stable nanoparticles witha size between 1 and 100 nm. They possess unique optical, physicochemical,electronic, and catalytic properties that make them applicable invarious fields. They are characterized by large surface area, distinctshape, stability, strong adsorption, absorption in the visible spectrumregion (with a possible shift to the UV–visible region dependingon the size and morphology), the possibility of functionalization,and optical properties dependent on the size. They present surfaceplasmon resonance, the ability for fluorescence quenching due to fluorescenceresonance energy transfer, and surface-enhanced Raman scattering (SERS).To improve the properties, stability, dispersity, functionality, andbiocompatibility, surface modification is required. Functionalizationis possible through covalent bonding, electrostatic interactions,and molecules binding.124 anionic contaminants,122 pesticides,and drugs.123Because of thesefeatures, AuNPs can be used in sensing and biosensing technologies,for instance, for the detection of metal ions,4.5nano-objects with two external dimensions in the nanoscaleand the third dimension significantly larger”.78 Various morphologies of NFs can be obtained,depending on the process conditions, e.g., smooth, beaded, hollow,or core–shell structures.125 NFsare characterized by excellent mechanical, physical, and chemicalproperties, including a high surface area to volume ratio and porosity.In addition, they offer flexibility in design, easy and low-cost fabrication,and a wide range of functionalization molecules and approaches.127Nanofibers are one-dimensional“128Electrospinning is one of the simplest and therefore commonlyused techniques for NFs fabrication. In short, after being electrified,a liquid droplet generates a jet, which is then stretched and elongated,creating fibrous structures. The basic setup includes a syringe filledwith a solution of a chosen polymer along with a syringe pump, a spinneret, a conductive collector (plate or rotating), anda high-voltage power supply. Charging of the liquid forces the dropletto form a Taylor cone, and the jet is ejected. The jet, initiallyin a straight line, undergoes whipping motions and stretching, solidifies,and is then collected on the collector in the form of nanofibrousmats or membranes.127 The incorporation of carbon NMs, metallic NPs, semiconducting NPs,conjugated polymers, or organic dyes  makesNFs a promising platform for sensing and biosensing  with polymers,followed by electrospinning of the solution, or through surface modificationof NFs by physical adsorption or suitable chemical reaction. The secondapproach is especially useful in sensing and biosensing, as the largesurface area allows the immobiliation or encapsulation of multiplemolecules, leading to improved sensing performance. Moreover, theuse of NFs does not contaminate the solution, as they can be easilyremoved from the sample after the detection.osensing 6.127,129127 environmental toxicants,134 cancer cells,135 and pH.133Nanofibers were applied in optical sensors forthe detection of,e.g., heavy metals,5137 Abnormal levels of these molecules, such as dopamine, epinephrine,serotonin, cortisol, etc. can be found in response to several conditions,such as emotional state  or inthe presence of various diseases, from neurodegenerative and cardiacpathologies to mental disorders and tumors.143 Therefore, it is very important to determine the concentration ofneurohormones in human biofluids  for disease prevention or diagnosis,in order to improve the quality of life and to minimize health risks.Concentrations of neurotransmittersproduced by the nervous systemand of hormones produced by glands are indicators of the body’sstate, and they are related to stress conditions.145 HPLC-MS,147 electrochemical methods,151 and UV–vis spectroscopy,152 have been developed. Despite their selectivityand sensitivity, most of these methods have some non-negligible drawbacks,such as consumption of time, high costs, qualified personnel need,and sometimes the need for additional steps. In this regard, optical(bio)sensors have appeared as promising useful analytical alternatives,possessing a limit of detection in the range of nanomolar or lessand high reproducibility and sensitivity, in addition to rapid response,easy analysis, and low costs. Considering these, fluorescence-based(bio)sensors that use fluorescent nanomaterials are, in general, veryuseful analytical tools thanks to their high sensitivity, biocompatibility,and photostability.141Owing to the low physiological concentrations of these biomarkers,ultrasensitive methods to carry out quantitative analysis in biologicalsamples are necessary. In recent years, numerous analytical strategies,including HPLC,5.1153 In medicine, it is mainly usedin the treatment of heart diseases, bronchial asthma, and anaphylacticshock.56 In free form, EP occurs as anorganic cation in central nervous system tissues and body fluids.154 Many diseases are closely related to changesin adrenaline levels—for example, low levels of adrenalinehave been found in patients with Parkinson’s disease.62 Hence, the quick and sensitive detection ofEP in body fluids is of key importance in medical diagnostics, pharmacology,and the control of nerve physiology.155 Currently, many tests for the determination of EP concentrationsare known, such as electrochemical methods,158 capillary electrophoresis,160 liquid chromatography,162 or chemiluminescence.164 Unfortunately, mostof these methods are limited by high costs, tedious operation, andthe need to prepare the sample for measurements in advance. In thecase of EP, there are almost no existing optical detection systems.It is much more difficult to detect EP because of its rapid metabolism,and in fact, it does not possess any fluorescence properties.155Adrenaline,also known as epinephrine (EP) 7, is one56 For this purpose,water-soluble CuInS2 quantum dots closed with l-cysteine were synthesized. In the next stage, positivelycharged EP was accumulated on the surface of quantum dots throughelectrostatic interactions and hydrogen bonds, resulting in the formationof electrostatic adrenaline–CuInS2 QDs complexes.The constructed system also uses tyrosinase, which can stimulate EPto generate H2O2 and additionally oxidizes adrenalineinto EP quinone. Both H2O2 and epinephrine quinonecan suppress CuInS2 fluorescence through an electron transferprocess. Under optimal conditions, the fluorescence -quenching coefficientwas proportional to the logarithm of the EP concentration in the concentrationrange of 1 × 10–8–1 × 10–4 mol L–1, while the detection limit was 3.6 nM.Z. Liu and S. Liu have developed a simple fluorescencebiosensorfor the detection of EP.153 A miniature biosensor based on low-temperaturecofiring ceramics technology (LTCC) was designed by the immobilizationof enzymes belonging to the class of oxidoreductases on the surface of a semiconducting polymer -4-(5-hexylthiophen-2-yl)pyridine)).The detection procedure was based on the oxidation of the substratein the presence of the enzyme. An alternative enzyme-free system resultedin the formation of a colored complex between Fe2+ ionsand EP molecules. Under optimized conditions, the sensor was characterizedby very high sensitivity and selectivity over a wide range of concentrationswith a detection limit of 0.14–2.10 nM. The constructed systemwas successfully used to determine EP in labeled pharmaceutical samples.Another method of detecting EP was proposed by Baluta and co-workers.2 solution.62 Visual detection was also possible by changingthe color of the solution from pale blue to red-brown. In this case,the CuCl2 solution is used as a probe to simplify the method,and its performance is comparable to that of fluorometric and colorimetricsensors. The created sensor is characterized by simplicity, high selectivity,and repeatable operation. In fluorometric detection, it showed activityin the linear range of 3 × 10–5–5 ×10–7 M, while in colorimetric detection in the rangeof 5 × 10–4–2 × 10–5 M. To confirm the commercial applicability, artificial urine andpharmaceutical preparations were successfully analyzed by the constructedtwo-channel sensor.Sivasankaran and Girish Kumar proposed a new EP detection strategybased on colorimetric and fluorescence measurements resulting fromthe formation of copper nanoparticles from a CuCl67 They selected 10 different DNA sequences tomodify the corona phase of CNTs and used near-infrared microscopyto measure the fluorescence of the obtained probes. In the case ofepinephrine, the limit of detection (LOD) was in the range of 0.5–33.3nM, depending on the oligonucleotide sequence used for the modification.The same experiment was repeated for dopamine and norepinephrine,with the LOD between 0.7 and 9438 nM and 0.5 and 23.7 nM, respectively.In addition, it was found that selected sensors were able to distinguishdifferent neurotransmitters at low concentrations of 50 nM.Mann et al. used SWCNTs functionalized withDNA to create a fluorescentsensor for the detection of catecholamine neurotransmitters.69 and exhibitedblue fluorescence. These NPs were applied for the detection of neurotransmitters,epinephrine, norepinephrine, and dopamine, via fluorescence recovery.In the proposed strategy, the system’s fluorescence intensitywas quenched by MnO4– and recovered withthe help of the analytes. The detection limits were 88, 91, and 140nM for EP, NE, and DA, respectively. Additionally, the system showedgood selectivity toward potential interfering agents and good recoveryvalues in real sample analysis.Highly crystalline nitrogen-doped fluorescent carbon nanoparticles(N-CNPs), synthesized from ethylene glycol and alanine anhydride,were developed by Das and DuttaThe sensor systems for the detectionof EP described above aresummarized in 5.264 Thedetermination of NE concentration is extremely important in modernmedical diagnostics, not only for the determination and study of thephysiological processes of this catecholamine but also for the diagnosisand monitoring of the course of treatment of cardiovascular diseasesand mental disorders.165 Moreover, overexpressionof both NE and EP in blood and urine may indicate the presence ofpheochromocytoma located in the adrenal medulla; however, the overexpressionof only NE suggests the presence of a tumor elsewhere. Hence, testsenabling the simultaneous measurement of NE and EP concentration inblood and urine are extremely useful, as thanks to them it is possibleto quickly diagnose the disease and implement appropriate treatment.166 Many methods for the detection of NE have beendescribed, such as electrochemical detection,168 capillary electrophoresis,169 and HPLC-basedmethods.170 The downside to using thesemethods is the need for expensive equipment and manpower. Therefore,it is necessary to find fast and sensitive methods for the determinationof this catecholamine in biological samples.Noradrenaline,also called norepinephrine (NE) 8, like E64 The basis of the detection strategy is the formation ofbrown silver nanoparticles (AgNPs) in the presence of NE, resultingin a strong fluorescent signal. The designed sensor is characterizedby a linear relationship between the absorbance values and the concentrationof NE in the range 1.00 × 10–6 −6.66× 10–8 M with a detection limit of 1.79 ×10–8 M. Additionally, it was found that the fluorescenceintensity was directly proportional to the concentration of NE inthe range 8.92 × 10–3–5.66 × 10–5 M with a LOD of 5.59 × 10–6 M. The system constructed in this way has been successfully usedto determine NE in synthetic blood serum, which indicates its potentialuse for diagnostic purposes.Menon et al. developed a two-channel colorimetricand fluorometricsensor for the sensitive and rapid detection of NE.48 During single-wavelengthexcitation, the hybrid nanoprobe generated double-emission peaks belongingto CDs and CdTe-QDs. The basis of the action was quenching of fluorescenceby EP or NE due to electron transfer from QDs to the oxidation productsof catecholamines. At the same time, the fluorescence intensity ofthe CDs remained unchanged. The relative ratios of the fluorescenceintensity of CDs and CdTe-QDs were directly proportional to the concentrationof catecholamines. The new fluorescence detection platform was fastand convenient and was used to detect EP and NE in human serum sampleswith satisfactory linear range results for NE from 0.005 to 10 μMand a LOD of 2.1 nM.Zhang and his team proposed a differentstrategy. They constructeda ratiometric fluorescent nanoprobe consisting of water-soluble fluorescentcarbon dots and 3-mercaptopropionic acid-coated cadmium telluridequantum dots (CdTe-QDs).2 quantum dots and molecularlyimprinted polymer (MIP) forsensitive and fast detection of NE.51 Theconstructed matrix was characterized by Fourier transform infraredspectroscopy, transmission electron microscopy, and fluorescence spectroscopy.The newly synthesized system was characterized by high selectivityand affinity for NE. The basis of the sensor operation was the measurementof the fluorescence intensity of CdTe@SiO2@MIP in the presenceof the tested catecholamine. The fluorescence intensity of the systemdecreased linearly with the increase of NE concentration in the rangeof 0.04–10 μM. The limit of quantification was set at8 nM. The constructed MIP-based nanoplatform was successfully usedin the analysis of NE concentration in the plasma of rats. Becauseof the simplicity and speed of the gun, it can potentially be usedto determine NE in medical diagnostics.Wei et al. designed a molecular imprintedsensor based on CdTe@SiO52 Forthis purpose, they carried out a MIP-anchoring process on the surfaceof two different colored quantum dots. The platform made of CdTe@SiO2 and CdTe/CdS/ZnS/SiO2 QDs was modified with templatesfrom NE and EP to obtain two matrices, NE-QD@MIP (for NE) and E-QD@MIP(for EP). Such constructed nanosensors were characterized by selectivityand high binding affinity to the appropriate matrix molecule. Thematrix mixture could be excited at the same excitation wavelength,and simultaneous detection of NE and EP could be accomplished by monitoringtwo different color fluorescence signals without spectral overlap.Under optimal conditions, the fluorescence intensity of the systemdecreased linearly with increasing concentration of the standard moleculein the linear range of 0.08–20 μM with a detection limitof 9 nM for NE and 12 nM for EP.Wei et al. also proposedanother MIP-based method for the sensitiveand rapid detection of NE and EP.171 developed astrategy based on excitation–emission fluorescence spectroscopyusing glutathione-capped CdSeS/ZnS quantum dots (QDs-GSH) for thedetection of various neurotransmitters, including EP, NE, GABA, andmore, because of the cross-affinity of the modified nanocrystals towarddifferent chemical structures of neurotransmitters. The proposed assayallowed the quantification of catecholamine neurotransmitters  at the micromolar concentration range.However, in the case of other tested neurotransmitters , the analysis of only specific compoundswas possible, limiting the future use of this method. The authorsstate that further research regarding the LOD, selectivity, and realsample analysis must be done.Głowacz et al.The sensor systems for the detectionof norepinephrine describedabove are summarized in 5.3180Dopamine (DA)9 is an e182 As the concentration of DA in real samples is very low, its determinationrequires very sensitive methods.In agreement with the Human Metabolome Database,the physiologicalconcentration of DA varies in different biofluids: in blood it isless than 130 pM, whereas in human cerebrospinal fluid and urine thelevels of dopamine are ≈5 nM and less than 1 μmol/mmolof creatinine, respectively.65 who realized a fluorescent biosensor based onin situ bifunctionalized carbon dots with boronic acid and amino groups(B–N-CDs). 3-Aminophenylboronic acid was used as the uniqueprecursor for modified CDs preparation using a simple hydrothermalapproach. The DA-sensing process was based on the interactions betweenthe amino groups on the CDs and DA, which enable the absorption ofDA onto the surface of the CDs through the formation of hydrogen bondsand on those of the boronic acid group (B(OH)2) with thediol moiety of DA (The best detection limit of0.1 pM with a wide linear range (from1 pM to 1 μM) was achieved by Liu and co-workers,ty of DA 10. Upon 73 using a sensor consisting of polypyrrole/graphenequantum dots (PPy/GQDs) core/shell hybrids , showing very good recovery values (97.6%–103.3%).A sensing process based on similar interactionsbetween oxygen-containinggroups and amino groups with DA was exploited by Zhou et al. hybrids 11, which66 The structure of these materials is still unknown,but their features of photostability, cell permeability, high brightness,and nontoxicity make them particularly suitable for use in sensing.The detection method was based on the quenching of the CNDs fluorescenceat 425 nm when excited at 310 nm. The proposed materials exhibiteda quantum yield up to 58%, allowing the achievement of very good performancesin terms of detection limit .A new class of carbogenic nanomaterials, highlybright multicolorfluorescent sulfur-doped carbon dots (CNDs), obtained by a single-stepreaction, was used for sensitive DA detection by Gupta and Nandi.59 in 2022. In this strategy, dopamine had a doublerole: the analyte and a spacer between Tb(III) and AuNFs, and electrostaticinteractions were mainly responsible for bonding between the Tb3+–DA complex and the NPs. The enhancement of the fluorescencesignal of the system was possible because of the metal-enhanced fluorescence,the Tb3+–DA combination, and the energy transferfrom the analyte to Tb3+. The results showed a wide linearrange (0.80–300 nM), a low LOD of 0.21 nM, and satisfactoryrecovery in serum and DA injection samples.Metal-enhanced fluorescence based on gold nanoflowers(AuNFs) forsensitive and selective DA detection was adopted by Li et al.9 and by Baluta et al.76 It is, in fact, well-known that DA tends to self-polymerize to polydopaminein alkaline conditions, and the polymer possesses fluorescence capability;therefore, it can be used for optical measurements.74 Weng and co-workers in 2015 and Baluta and co-workers in2017 reported rapid and easy fluorescence-sensing strategies basedon the polydopamine thin film formed and absorbed on the surface ofGQDs. In both cases, the detection process was due to the quenchingof fluorescence which occurred through FRET. Baluta and co-workers76 were also responsible for the design and developmentof an enzyme-based fluorescent biosensor consisting of a low-temperaturecofired ceramic platinum electrode (LTCC-Pt) covered with a thin filmof poly(dithienotetraphenylsilane) and GQDs on which laccase had beenimmobilized. The idea to use laccase was derived from the fact thatit catalyzes DA oxidation to dopamine-o-quinone,which is unstable and rapidly polymerizes in an alkaline environmentto polydopamine, which is the desired species for the detection process.Detection limits between 8 and 80 nM were achieved using these strategies.These values do not allow the use of the just-described (bio)sensorsin biological samples, but they are, however, suitable for the analysisof DA-containing drugs .A different sensingprocess approach based on the DA polymerizationwas successfully exploited in different ways by Weng et al.54 in 2016. It is a systembased on [Ru(bpy)2dppz]2+  and thioglycolicacid (TGA)-capped CdTe quantum dots for DA, adenosine, and 17β-estradioldetection. The mechanism was based on the ionic conjugation betweenthe Ru complex and QDs due to their electrostatic attraction in anaqueous solution that causes a decrease in the fluorescent intensityof QDs. After the addition of an adequate aptamer DNA, the fluorescenceof QDs can be recovered thanks to the strong tendency of DNA to bindto the Ru complex. When the aptamer was first incubated with the targetanalyte, it could not bind to the Ru complex, and the fluorescencewas quenched. It is a very highly selective and sensitive method thattakes advantage of the aptamer specificity and the excellent fluorescenceproperties of CdTe-QDs. In addition, the authors declare that thismethod is one of the simplest and one of the first that can detectthese three analytes by one universal system.Anotherbiosensor, specifically a fluorescent aptasensor, was developedby Huang et al.57 who reported the developmentof a nanosensor for DA and glutathione detection in human serum sampleswith satisfactory results. The particularity of this device is thatit can be considered a double sensor: (i) dopamine–quinonederived from the oxidation of DA, adsorbed on the surface of silicadue to hydrogen bonds and electrostatic interactions, can be determinedby the quenching of the photoluminescence of the modified CdTe-QDs,and (ii) glutathione, which is a strong reducing species, can be determinedthrough the restoring of the fluorescence of QDs due to the reductionof dopamine–quinone.CdTe-QDs coatedwith silica were used as fluorescent probes byXiangzhao et al.,55 and Zhao et al.,53 who synthesized, as DA sensors, adenosine-capped CdSe/ZnSquantum dots (A-QDs) and (3-aminopropyl)triethoxysilane (APTES)-cappedZnO-QDs, respectively. In both cases, QDs were water-soluble, andthe sensing processes were based on the fluorescence quenching ofthe QDs caused by an electron transfer. Mu and co-workers55 achieved a detection limit of 29.3 nM, highselectivity, and satisfactory recovery values (94.80%–103.40%)in human urine samples. Likewise, APTES-ZnO-QDs allowed a LOD valueof 12 nM to be obtained with no significant interference effects froma wide plethora of common molecules present in human blood serum.The optimum features of modifiedQDs were also exploited by Muet al.70 described a novel aptamer-basedbiosensor for dopamine determination using fluorescence energy transferbetween a nanomaterial—single-wall carbon nanohorns (SWCNHs)—anda fluorescein derivative. In the proposed strategy, an aptamer waslabeled with 5-carboxyfluorescein (FAM) and, because of π–πinteractions, could be absorbed on the surface of SWCNHs, which ledto a decrease in fluorescence intensity. In contrast, in the presenceof DA, a G-quadruplex formed when the analyte bonded to the labeledaptamer could not interact with the NM surface, resulting in the recoveryof fluorescence. The platform exhibited a linear range of 0.02–2.2mM and a detection limit of 5 μM, and its applicability wasconfirmed by the analysis of dopamine-spiked serum samples.Zhang et al.5.4174 Numerous studies have been conducted to find an effective and efficientmethod of production of this neurotransmitter—currently, GABAis produced in pharmaceuticals and food in sprouted brown rice, anaerobicallyincubated tea leaves, or fermented milk products.176 Unfortunately, owing to the zwitterionic nature of GABA (the aminoand carboxyl groups are adequately protonated and deprotonated), thedetection of these compounds is an extremely difficult task; hence,the design of sensor devices is quite a challenge.177Gamma-aminobutyric acid (GABA) 12 is one183 Usually, serotonin contributes to the feelings of happiness, andfor this reason it is also used as a drug for depression therapy.75 However, the actual biological function of serotonin is complexand multifarious, and its low levels can be synonymous of depression,anxiety neurosis, obsessive–compulsive disorder, and migraines.Conversely, extremely high levels of serotonin could cause fatal serotoninsyndrome because of its toxicity, as well as irritable bowel syndrome.63 A typical concentration of 5-HT in whole blood and in platelet-poorplasma was found at 774 ± 249 and 5.17 ± 4.17 nM, respectively,184 between 0.52 and 1.2 nM in cerebrospinal fluid,185 and in the range 10–78 μmol/molcreatinine in urine.186Serotonin 13, also 187 Anomalous increments in cortisolconcentration can inhibit inflammation, depress the immune system,and increase fatty and amino acid levels in blood. Extremely highlevels can cause Cushing’s disease, while decreased cortisollevels lead to Addison’s disease.188 Levels of this hormone in saliva closely reflect the levels of unboundcortisol in blood; hence, saliva is the most preferred sample foranalysis.189 Cortisol levels in the bodyfluctuate during the day between 5 nM and hundreds of nanomoles, reachinga minimum of <2 nM in the evening or at midnight.46Cortisol 14, also As in the case of DA, researchers are trying todevelop increasinglysensitive methods for the determination of GABA, 5-HT, and cortisol.Compared to what has been observed for DA, nanomaterial-based fluorescent(bio)sensors for the detection of GABA, 5-HT, and cortisol are fewer,and the most recent are reported in the following paragraphs.71 In orderto obtain the detection platform, the functionalization of the CDswas performed with 3-aminophenylboronic acid (APBA) and nicotinamideadenine dinucleotide phosphate (NADP+) by means of an ECD/NHScoupling reaction. The CDs modified in this way, together with theenzyme GABase, were used for the determination of GABA by fluorescencequenching due to electron transfer between the enzyme and the substrate,thanks to the formation of a reduced form of NADPH. The system constructedin this way enabled the determination of the GABA concentration inthe linear range of 0–90 μM with a detection limit of6.46 μM. The performance of the sensor has been confirmed bytesting on biological samples, such as human spinal fluid and serum.Sangubotla and Kim developed a fluorescent enzyme sensor usingnontoxic carbon dots synthesized from corn juice for the sensitiveand rapid detection of GABA.178 The surface of the optical fiberwas modified with QDs via an EDC/NHS coupling reaction. Then, thefunctionalization of the QDs was performed using 3-aminophenylboronicacid and NADP+. The basis of the detection was the measurementof the change in the intensity of the QDs fluorescence, which occursdue to the transfer of electrons from the QDs to NADP+.The use of the GABase enzyme in the system allowed the reduction ofNADP+ to NADPH during the conversion of GABA to succinicacid. The reduction of NADP+ to NADPH made it difficultto transfer electrons, which made it possible to return the fluorescenceintensity of the QDs to the initial state.Zhao et al. constructed a quantum dot fiber optic sensor for thedirect detection of GABA by quenching and fluorescence recovery ofQDs.2+-dopedZnS-QDs modified with silica nanoparticlesbased on molecularly imprinted polymers (SiO2@MIPs) weredesigned and realized by Wang et al.50 Insuch a device, advantages of QDs such as large Stokes shift, low backgroundnoise, and a narrow and symmetric emission spectrum have been combinedwith the peculiar feature of the MIPs to mimic a natural receptor.As a matter of fact, the sensing process was based on the formationof a complex between the amino group present in QDs@SiO2@MIPs and the hydroxyl group of 5-HT, which led to the quenchingof the QD fluorescence  was instead employed by Zhao and co-workers63 Gold nanoclustersas well as QDs possess a large Stokes shift, good photostability,and ultrasmall size. In particular, the system developed by Sha etal. is based on the use of transferrin-encapsulated gold nanoclusters(Tf–Au-NCs) because of the well-known high affinity betweensialic acid (SA) and 5-HT,191 due to the presenceof SA residues in transferrin. Moreover, transferrin, with 40 cysteineand 26 tyrosine fragments in its chain, is a very suitable reducingand stabilizing agent for gold nanoclusters. The obtained biosensoris a turn-on type device, as it showed an aggregation-enhanced emissionof Tf–Au-NCs in the presence of 5-HT. With a detection limitof 0.049 μM and a linear range of 0.2–50 μM, itwas applied for 5-HT quantification in human serum.A devicefor the highly selective detection of 5-HT, based on anew class of nanomaterials, gold nanoclusters (AuNCs), was developedin 2019 by Sha and co-workers.50 the advantageous feature of the molecular imprintingtechnology to obtain a tailor-made specific binding cavity for a certaintarget molecule was also exploited by Murase and co-workers192 in the construction of a sensor for cortisoldetection. They reported the synthesis of a fluorescence polarizationassay platform based on core–shell-type molecularly imprintedpolymer particles (MIP-NPs) using cortisol-21-monomethacrylate asa template agent. The sensing process was based on the competitivebinding of dansyl-labeled cortisol and cortisol against the cortisol-imprintednanocavities. The just-mentioned device exhibited a detection limitof ca. 80 nM, and it showed no effects of progesterone interference.Similarlyto the 5-HT sensor developed by Wang et al.,46 reported instead two new fluorescence biosensors,one based on cortisol-selective aptamers conjugated on the CdSe/ZnScore–shell QDs surfaces and the other on anticortisol antibodiesconjugated to the same ones. In both cases, the modified QDs werecarried by magnetic nanoparticles in order to facilitate probe conjugationand cortisol detection in saliva samples. In the presence of cortisol,the authors observed fluorescence quenching of QDs sensorics development from a construction pointof view are presented.193 The most approachable in this context are microfluidicdevices, which often are used in miniaturized optical bioanalyticalsystems. Microfluidic approaches, which can be compared to miniaturizedforms of biochemical laboratories, allow the execution of many analysesat the same time, mixing or separation of reagents, biochemical reactionmonitoring, and signal output.195 However, despite theseadvantages, as well as many available sources describing the operationof miniaturized optical sensors/biosensors, also based on microfluidicplatform-assisted miniaturized biosensing systems, there is stilla problem with many analysis steps and with the integration of samplepretreatment. Microfluidic systems could overcome these problems tosome extent; however, the main challenge still remains—to developa fully integrated detection system in a solid and approachable format.Apart from the most important workingparameters of biosensorsfor diagnostic application, which are sensitivity and selectivity,devices for clinical application should allow miniaturization withsimultaneous integration, automatization, and multiplex detectionwithout the need for sophisticated apparatus and trained personnel.197 Additionally, biosensors canbe combined with smartphones as their cameras, light sources, imageprocessing, and communication possibilities can lower costs and simplifydistribution on a large scale and reduce the time of work.198 Such types of chips can be used to measuresignals directly from patient samples, analyze data with personalizedapplications, and wirelessly send the results for interpretation.199 With the use of microfluidic-based biodevices,costs could be reduced thanks to using low-cost material and small-volumereagent requirements.Another important issue is cost-effectiveness. It is importantin sensor development to use ecofriendly, nontoxic, and relativelycheap components. Solutions may be to use stable mass production thatwill reduce costs or to focus on inexpensive disposable chips withreplaceable components that can avoid cross-contamination problemsand complicated cleaning procedures when handling biological samples,i.e., integration schemes that enable disposable cartridges and stand-alonereaders.To summarize, apart from manipulationswithin sensitive and selectivedetection , integration,coherence, and miniaturization are the most important challenges facingbiosensors in the context of their commercialization. The use of fluorescentmethods for the determination of medically important neurohormonesdescribed in this Review only highlights the need to introduce suchdevices to the market as soon as possible, as neurohormones are indicatorsof the body’s homeostasis.


Since the advent of semiconductor detectors, they have been developed for several generations, and their performance has been continuously improved. In this paper, we propose a new silicon drift detector structure that is different from the traditional spiral SDD structure that has a gap between the cathode ring and the width of cathode ring, increasing gradually with the increase of the radius of the cathode ring. Our new structure of spiral SDD structure has equal cathode ring gap and a given surface electric field, which has many advantages compared with the traditional structure. The novel SDD structure controllably reduces the area of silicon oxide between the spiral rings, which in turn reduces the surface leakage current due to the reduction of total oxide charge in the silicon oxide and electronic states on the silicon/silicon oxide interface. Moreover, it has better controllability to adjust this spiral ring cathode gap to achieve better surface electric field distribution, thus realizing the optimal carrier drift electric field and achieving the optimal detector performance. In order to verify this theory, we have modeled this new structure and simulated its electrical properties using the Sentaurus TCAD tool. We have also analyzed and compared different spiral ring cathode gap structures (from 10 µm to 25 µm for the gap). According to the simulation results of potential, electric field, and electron concentration, we have obtained that a spiral ring cathode gap of 10 µm has the best electrical characteristics, more uniform distribution of potential and surface electric field, and a more smooth and straight electron drift channel. Since the concept of silicon drift detector (SDD) was first proposed by E. Gatti and P. Rehak in the 1980s ,3,4, nucTo optimize the drift behavior of carriers in SDDs and reduce their surface leakage current, we propose a new detector structure based on controlling spiral ring cathode gap, namely, to keep it small and unchanged. Relative to the traditional design that the gap gradually increases with ring radius, this new structure will greatly reduce the silicon oxide area. This in turn can greatly reduce surface leakage current caused by the electronic states in silicon oxide and on the silicon/silicon oxide interface. At the same time, in the design, we can reasonably adjust the given surface electric field according to the actual application to achieve better carrier drift electric field and minimize surface current of the detector, so as to form a fully depleted detector region and realize a high-quality SDD. In this paper, simulations and performance comparisons are performed using the technical computer aided design (TCAD) tool for spiral ring cathodes with equal gaps of 10 µm and 25 µm, respectively, for a given surface electric field. Systematic comparative analysis can also be performed for surface electric fields in subsequent work.Considering the dead space and the symmetry of the physical structure of the detector when it is made into an array, we chose a double-sided hexagonal detector structure in our case of simulation. The shape of the detector is hexagonal, with a diagonal length of 3000 µm and a thickness of 300 µm. The detector bulk is lightly doped N-type silicon substrate with a doping concentration of An appropriate potential gradient is established for the carrier drifting from the position of incident particle to the collection anode by adjusting the cathode gap effectively and controllably to divide the voltage and to fully deplete the detector. Given the surface electric fields on both surfaces, the depletion region within SDD forms a transverse drift electric field that generates a drift channel. When the incident particle induced free carriers enter the drift channel, they drift to the collection anode through the transverse drift electric field, converting the energy of the incident particle into an electrical output signal. This output signal may be used to detect or identify the incident particle or light.Between each neighboring two spiral rings at a radius of geometry , for a hHere, the helix satisfies the following conditions:Given the surface electric field and equal (constant) gap, the formula of pitch The angle eference :(7)φ(r)=Here, Let:Let:Then If Here, Since, Since:Surface potential Let:Then If Again, if In this paper, the purpose is reducing the surface current and obtaining the minimum leakage current by effectively and controllably adjusting the cathode gap One can solved For the case of The detector structure used in this paper can be derived from calculations using Equation (29) and related parameters in the design. It was mentioned in  that the silicon , and d iUsing this set of bias voltages, we have simulated this structure using the Sentaurus TCAD tool with results shown in Shown in The thick black line in According to the basic principles of physics, we know that the electric field is the gradient of the electric potential, so we can roughly judge the distribution of the electric field according to the potential distribution in The entire detector is in a non-zero electric field environment and is completely depleted. From As shown in The two-dimensional position resolution sensitivity in the detector is achieved by using the timing of electrons arriving at the collection anode to determine one of the dimensions of position, since the distance of arriving electrons to the collection anode is simply the drift time (timing) times the drift velocity (= electron mobility times drift field In this study, we proposed a new semiconductor detector structure of helical silicon drift detector with equal cathode ring gap and given surface electric field. This new structure reduced detector surface area, which in turn reduced the detector surface leakage current and made the detector internal electric field more uniform. We simulated and analyzed the internal characteristics of the detector with different spiral ring cathode gaps. We obtained the potential, electric field, and electron concentration distribution in order to determine the optimal detector parameters. Simulations were performed to compare two detectors with different spiral ring cathode gaps, and we determined that the performance of the spiral ring cathode gap of 10 µm was superior to the spiral ring cathode gap of 25 µm.This study provides strong theoretical support for practical fabrication of the detector. The new detector structure can be applied to the fields of space physics and photon science, such as pulsar X-ray detection and X-ray fluorescence spectrometers.