Reversible deactivation of higher-order posterior parietal areas. I. Alterations of receptive field characteristics in early stages of neocortical processing.

Somatosensory processing in the anesthetized macaque monkey was examined by reversibly deactivating posterior parietal areas 5L and 7b and motor/premotor cortex (M1/PM) with microfluidic thermal regulators developed by our laboratories. We examined changes in receptive field size and configuration for neurons in areas 1 and 2 that occurred during and after cooling deactivation. Together the deactivated fields and areas 1 and 2 form part of a network for reaching and grasping in human and nonhuman primates. Cooling area 7b had a dramatic effect on receptive field size for neurons in areas 1 and 2, while cooling area 5 had moderate effects and cooling M1/PM had little effect. Specifically, cooling discrete locations in 7b resulted in expansions of the receptive fields for neurons in areas 1 and 2 that were greater in magnitude and occurred in a higher proportion of sites than similar changes evoked by cooling the other fields. At some sites, the neural receptive field returned to the precooling configuration within 5-22 min of rewarming, but at other sites changes in receptive fields persisted. These results indicate that there are profound top-down influences on sensory processing of early cortical areas in the somatosensory cortex.

Understanding immune-mediated titanium allergy to in situ orthopaedic implants: a narrative review of the current literature.

INTRODUCTION: Clinical recognition of potential immune-mediated allergic responses to implanted metal devices is increasing. For orthopaedic implants, while 'pure' compounds are used in specific circumstances, the majority of components are alloys - a combination of two or more distinct metals. Titanium is found commonly in many orthopaedic devices and is often championed as a 'hypoallergenic' option or inclusion. In the absence of a relevant previously published summary on the topic, this paper explores the current state-of-understanding of titanium allergy and proposes a patient management algorithm whereby such immune reactions are clinically-suggested. METHODS: A structured, systematic literature review was performed following PRISMA search principles to provide a contemporary summary-of-understanding in this area and to highlight clinical and knowledge deficiencies. RESULTS: Thirty-five topic-related articles were identified, the majority reflecting small case series' or proof-of-concept studies. The general standard of scientific evidence available was poor. Justification for arthroplasty utilization of titanium as a 'hypoallergenic' option is largely extrapolated from non-orthopaedic domains. CONCLUSIONS: Both ionic and conjugated titanium particles released from implant surfaces have the potential to trigger innate immune responses and true allergy. There exists no simple, high-sensitivity, screening test for titanium allergy. Conventional skin-patch testing is unreliable due to poor dermal penetration. Given established lymphocyte and macrophage activation pathways for allergy responses, in vitro methods using both cell-types show diagnostic promise. Surgical biopsy analysis from host-implant interfaces remains the contemporary 'gold-standard', however this represents an invasive, costly and highly-specialized approach not readily available in most settings. Further research to establish reliable/accessible diagnostic methods are indicated.

Understanding immune-mediated cobalt/chromium allergy to orthopaedic implants: a meta-synthetic review.

BACKGROUND: The frequency of primary joint replacement surgery continues to increase worldwide. While largely considered biologically inert entities, an increasing body of evidence continues to validate a not insignificant incidence of allergic reactions to such implants. Little previous work has explored genuinely immune-mediated reactivity in this context. In the absence of a contemporary published summary on the topic, this paper explored the current state of understanding of cobalt/chromium allergy and proposes a patient management algorithm whereby such immune reactions are clinically suggested. METHODS: A structured, systematic literature review was performed by following PRISMA search principles to provide an updated review of this area. RESULTS: Thirty-six topic-related articles were identified, the majority reflecting lower tiers of scientific evidence with a lack of homogeneous quantitative data to facilitate valid cohort comparisons. Largely, the available literature represented small case series' or expert opinions. CONCLUSIONS: Despite increasing clinical awareness and acknowledgement of true allergy to joint replacement components, this review highlighted that the evidence base underpinning the diagnosis and management of such patients is limited. Both patient-reported metal allergy or skin patch testing are grossly unreliable methods and show almost no correlation with true immune reactivity. Recent studies suggested a potential role for patient-specific in vitro cellular activation testing and/or targeted genetic testing when cobalt/chromium allergy is clinically suspected. However, while likely representing the contemporary "best available" approaches both can be costly undertakings, are not yet universally available, and still require broader validation in non-research settings before wider uptake can be championed.

The Medicare Care Choices Model was associated with reductions in disparities in the use of hospice care for Medicare beneficiaries with terminal illness.

OBJECTIVE: To assess the effects of the Medicare Care Choices Model (MCCM) on disparities in hospice use and quality of end-of-life care for Medicare beneficiaries from underserved groups-those from racial and ethnic minority groups, dually eligible for Medicare and Medicaid, or living in rural areas. DATA SOURCES AND STUDY SETTING: Medicare enrollment and claims data from 2013 to 2021 for terminally ill Medicare fee-for-service beneficiaries nationwide. STUDY DESIGN: Through MCCM, terminally ill enrolled Medicare beneficiaries received supportive and palliative care services from hospice providers concurrently with curative treatments. Using a matched comparison group, we estimated subgroup-specific effects on hospice use, days at home, and aggressive treatment and multiple emergency department visits in the last 30 days of life. DATA COLLECTION/EXTRACTION METHODS: The sample included decedent Medicare beneficiaries enrolled in MCCM and a matched comparison group from the same geographic areas who met model eligibility criteria at time of enrollment: having a diagnosis of cancer, congestive heart failure, chronic obstructive pulmonary disease, or HIV/AIDS; living in the community; not enrolled in the Medicare hospice benefit in the previous 30 days; and having at least one hospital stay and three office visits in the previous 12 months. PRINCIPAL FINDINGS: Eligible beneficiaries from underserved groups were underrepresented in MCCM. MCCM increased enrollees' hospice use and the number of days at home and reduced aggressive treatment among all subgroups analyzed. MCCM also reduced disparities in hospice use by race and ethnicity and dual eligibility by 4.1 (90% credible interval [CI]: 1.3-6.1) and 2.4 (90% CI: 0.6-4.4) percentage points, respectively. It also reduced disparities in having multiple emergency department visits for rural enrollees by 1.3 (90% CI: 0.1-2.7) percentage points. CONCLUSIONS: MCCM increased hospice use and quality of end-of-life care for model enrollees from underserved groups and reduced disparities in hospice use and having multiple emergency department visits.

Silicon on ultra-low-loss waveguide photonic integration platform.

We demonstrate a novel integrated silicon and ultra-low-loss Si3N4 waveguide platform. Coupling between layers is achieved with (0.4 ± 0.2) dB of loss per transition and a 20 nm 3-dB bandwidth for one tapered coupler design and with (0.8 ± 0.2) dB of loss per transition and a 100 nm 3-dB bandwidth for another. The minimum propagation loss measured in the ultra-low-loss waveguides is 1.2 dB/m in the 1590 nm wavelength regime.

Incidental DCIS within a fibroadenoma.

A female in her early 20s was referred to the breast-endocrine surgeons with a self-detected tender left breast lump on the background of a family history of breast cancer. A physical examination revealed a rubbery and mobile mass in the left upper breast. Ultrasound demonstrated a solid hypoechoic mass with a likely differential diagnosis of fibroadenoma, with a subsequent core needle biopsy (CNB) confirming a fibroadenoma. Given the size and tenderness of the lump, an excisional biopsy was performed. Histology revealed a fibroadenoma with components of low-grade ductal carcinoma in situ, contained within the fibroadenoma and excised with clear margins.Following surgical excision, a multidisciplinary review determined that no further local therapy was required and recommended a genetics referral. This case was interesting as it raised important questions, including what the best surveillance strategies are for female patients with breast cancer within fibroadenoma and determining the risk and probability of missing epithelial atypia via CNB.

Optimizing clinical guidelines to address antimicrobial-resistant infections: A conceptual framework reflecting stakeholder perspectives.

Objectives: Clinical guidelines or guidance is an important tool for preventing and treating antimicrobial-resistant (AMR) infections. We sought to understand and support the effective use of guidelines and guidance for AMR infections. Methods: Key informant interviews and a stakeholder meeting on the development and use of guidelines and guidance for management of AMR infections; the interview findings and meeting discussion informed a conceptual framework for AMR infection clinical guidelines. Participants: Interview participants included experts with experience in guidelines development and physician and pharmacist hospital leaders and antibiotic stewardship program leaders. Stakeholder meeting participants included federal and nonfederal participants involved in research, policy, and practice related to prevention and management of AMR infections. Results: Participants described challenges related to timeliness of guidelines, methodologic limitations of the development process, and issues with usability across a range of clinical settings. These findings, and participants' suggestions for mitigating the challenges identified, informed a conceptual framework for AMR infection clinical guidelines. The framework components include (1) science and evidence, (2) guideline and guidance development and dissemination, and (3) implementation and real-world practice. These components are supported by engaged stakeholders whose leadership and resources help to improve patient and population AMR infection prevention and management. Conclusions: Use of guidelines and guidance documents for management of AMR infections can be supported through (1) a robust body of scientific evidence to inform guidelines and guidance; (2) approaches and tools to support timely, transparent guidelines that are relevant and actionable for all clinical audiences; and (3) tools to implement guidelines and guidance effectively.

Medicare Care Choices Model Improved End-Of-Life Care, Lowered Medicare Expenditures, And Increased Hospice Use.

The Medicare Care Choices Model (MCCM) tested a new option for eligible Medicare beneficiaries to receive conventional treatment for terminal conditions along with supportive and palliative care from participating hospice providers. Using claims data, we estimated differences in average outcomes from enrollment to death between deceased MCCM enrollees and matched comparison beneficiaries who received usual services covered by original Medicare. Enrollees were 15 percentage points less likely to receive an aggressive life-prolonging treatment at the end of life and spent more than five more days at home. MCCM also reduced net Medicare expenditures by 13 percent, decreased inpatient admissions by 26 percent, reduced outpatient emergency department visits by 12 percent, and increased hospice use by 18 percentage points. Although the Centers for Medicare and Medicaid Services did not expand the model, given concerns about generalizability, these results provide evidence that MCCM is a promising approach to transforming care delivery at the end of life.

Development of claims-based measures of unplanned acute care with superior power for assessing the effectiveness of interventions following acute care.

OBJECTIVE: To develop outcome measures that are more sensitive than current measures for evaluating primary or transitional care after hospitalizations, emergency department (ED) visits, or observation stays. DATA SOURCES: Medicare claims data from January 1, 2015, to October 31, 2017, for 1 261 707 Medicare fee-for-service beneficiaries served by (a) primary care practices participating in Track 1 of the Comprehensive Primary Care Plus (CPC+) initiative, and (b) their matched comparison practices. STUDY DESIGN: Given the poor statistical power in many studies to detect effects on readmissions, we developed two novel claims-based measures of unplanned acute care (UAC) following an index acute care event. The first measure assesses the proportion of hospitalizations followed by an unplanned readmission, ED visit, or observation stay within 30 days of discharge; the second assesses the proportion of ED visits and observation stays followed by a hospitalization, ED visit, or observation stay within 30 days. We calculate minimum detectable effects (MDEs) for both measures and for a conventional measure of 30-day unplanned readmissions, using CPC+ data. PRINCIPAL FINDINGS: Repeat UAC events are common among Medicare beneficiaries served by the CPC+ practices. In 2017, 22% of discharges and 21% of ED visits and observation stays had a UAC event within 30 days. Readmissions were the most common UAC event following discharge, whereas ED visits were most common following index ED visits or observation stays. MDEs are 25%-40% lower for the new measures than for the standard 30-day readmissions measure, indicating better statistical power to detect impacts of primary or transitional care interventions. CONCLUSIONS: This study introduces two new claims-based measures to assess quality of care during a patient's vulnerable period following acute care. The new measures complement existing measures, covering a broader range of UAC events than the standard 30-day readmissions measure, and yielding greater statistical power.

Effects of care coordination on hospitalization, quality of care, and health care expenditures among Medicare beneficiaries: 15 randomized trials.

CONTEXT: Medicare expenditures of patients with chronic illnesses might be reduced through improvements in care, patient adherence, and communication. OBJECTIVE: To determine whether care coordination programs reduced hospitalizations and Medicare expenditures and improved quality of care for chronically ill Medicare beneficiaries. DESIGN, SETTING, AND PATIENTS: Eligible fee-for-service Medicare patients (primarily with congestive heart failure, coronary artery disease, and diabetes) who volunteered to participate between April 2002 and June 2005 in 15 care coordination programs (each received a negotiated monthly fee per patient from Medicare) were randomly assigned to treatment or control (usual care) status. Hospitalizations, costs, and some quality-of-care outcomes were measured with claims data for 18 309 patients (n = 178 to 2657 per program) from patients' enrollment through June 2006. A patient survey 7 to 12 months after enrollment provided additional quality-of-care measures. INTERVENTIONS: Nurses provided patient education and monitoring (mostly via telephone) to improve adherence and ability to communicate with physicians. Patients were contacted twice per month on average; frequency varied widely. MAIN OUTCOME MEASURES: Hospitalizations, monthly Medicare expenditures, patient-reported and care process indicators. RESULTS: Thirteen of the 15 programs showed no significant (P<.05) differences in hospitalizations; however, Mercy had 0.168 fewer hospitalizations per person per year (90% confidence interval [CI], -0.283 to -0.054; 17% less than the control group mean, P=.02) and Charlestown had 0.118 more hospitalizations per person per year (90% CI, 0.025-0.210; 19% more than the control group mean, P=.04). None of the 15 programs generated net savings. Treatment group members in 3 programs (Health Quality Partners [HQP], Georgetown, Mercy) had monthly Medicare expenditures less than the control group by 9% to 14% (-$84; 90% CI, -$171 to $4; P=.12; -$358; 90% CI, -$934 to $218; P=.31; and -$112; 90% CI, -$231 to $8; P=.12; respectively). Savings offset fees for HQP and Georgetown but not for Mercy; Georgetown was too small to be sustainable. These programs had favorable effects on none of the adherence measures and only a few of many quality of care indicators examined. CONCLUSIONS: Viable care coordination programs without a strong transitional care component are unlikely to yield net Medicare savings. Programs with substantial in-person contact that target moderate to severe patients can be cost-neutral and improve some aspects of care. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00627029.

Estimating the hospital costs of inpatient harms.

OBJECTIVE: To estimate the additional hospital costs associated with inpatient medical harms occurring during an index inpatient admission and costs from subsequent readmissions within 90 days. DATA SOURCE: 2009 to 2011 Healthcare Cost and Utilization Project's State Inpatient Databases from 12 states. STUDY DESIGN: We compare hospital costs incurred by patients experiencing a specific harm during their hospital stay to the costs incurred by similar patients who did not experience that harm. DATA EXTRACTION: We extracted records for adult patients admitted for a reason other than rehabilitation or mental health, were at risk of a harm, and were admitted for less than a year. PRINCIPAL FINDINGS: The costliest inpatient harms, such as surgical site infections and severe pressure ulcers, are associated with approximately $30 000 in additional index stay costs per harm. Less costly harms, such as catheter- or hospital-associated urinary tract infections and venous thromboembolism, can add $6000 to $13 000. Birth and obstetric traumas add as little as $100. CONCLUSIONS: Our analysis represents rigorous estimates of the hospital costs of a variety of inpatient harms; these should be of interest to health care administrators and policy makers to identify areas for cost savings to the health care system.

15-site randomized trial of coordinated care in Medicare FFS.

Medicare beneficiaries in fee-for-service (FFS) who had chronic illnesses and volunteered to participate in 15 care coordination programs were randomized to treatment or control status. Nurses provided patient education (mostly by telephone) to improve adherence and ability to communicate with physicians. Patients were contacted an average of two times per month. The findings after 2 years are not encouraging. Few programs improved patient behaviors, health, or quality of care. The treatment group had significantly fewer hospitalizations in only one program; no program reduced gross or net expenditures. However, effects may be observed when 4 years of followup are available and sample sizes increase.

Impacts of a disease management program for dually eligible beneficiaries.

The LifeMasters Supported SelfCare demonstration program provides disease management (DM) services to Florida Medicare beneficiaries who are also enrolled in Medicaid and have congestive heart failure (CHF), diabetes, or coronary artery disease (CAD). The population-based program provides primarily telephonic patient education and monitoring services. Findings from the randomized, intent-to-treat design over the first 18 months of operations show virtually no overall impacts on hospital or emergency room (ER) use, Medicare expenditures, quality of care, or prescription drug use for the 33,000 enrollees. However, for beneficiaries with CHF who resided in high-cost South Florida counties, the program reduced Medicare expenditures by 9.6 percent.

Manually operatable on-chip bistable pneumatic microstructures for microfluidic manipulations.

Bistable microvalves are of particular interest because of their distinct nature of requiring energy consumption only during the transition between the open and closed states. This characteristic can be highly advantageous in reducing the number of external inputs and the complexity of control circuitries since microfluidic devices as contemporary lab-on-a-chip platforms are transferring from research settings to low-resource environments with high integrability and a small form factor. In this paper, we first present manually operatable, on-chip bistable pneumatic microstructures (BPMs) for microfluidic manipulation. The structural design and operation of the BPM devices can be readily integrated into any pneumatically powered microfluidic network consisting of pneumatic and fluidic channels. It is mainly composed of a vacuum activation chamber (VAC) and a pressure release chamber (PRC), of which users have direct control through finger pressing to switch either to the bistable vacuum state (VS) or the atmospheric state (AS). We have integrated multiple BPM devices into a 4-to-1 microfluidic multiplexor to demonstrate on-chip digital flow switching from different sources. Furthermore, we have shown its clinical relevance in a point-of-care diagnostic chip that processes blood samples to identify the distinct blood types (A/B/O) on-chip.

Stereomask lithography for multi-protein patterning.

The advances of biologically-friendly micropatterning technologies have benefited many areas of biological and medical research, including quantitative biochemical assay, point-of-care devices, biosensing and regenerative medicine. Conventional micropatterning techniques, for example, photolithography and soft lithography, have seen encouraging adaptation to creating biological micropatterns in the last decades. However, they still have not completely addressed the major needs of constructing multi-object biological microarrays with single-cell resolution without requiring cleanroom access. In this chapter, we present a novel versatile biological lithography technique to achieve integrated multi-object patterning with high feature resolution and high adaptability to various biomaterials, referred to as stereomask lithography (SML). A novel three-dimensional stereomask has been developed for successive patterning of multiple objects. The stereomask consists of both patterned through holes, which layout new micropatterns and non-through recesses, which protect pre-existing features on the substrate. Furthermore, high-precision reversible alignment among multiple bio-objects is achieved by adopting a peg-in-hole design between the substrate and stereomasks. As demonstration, we have successfully used the SML technique to construct complex biological microenvironment with various bio-functional components at single-cell resolution.

Smartphone-interfaced lab-on-a-chip devices for field-deployable enzyme-linked immunosorbent assay.

The emerging technologies on mobile-based diagnosis and bioanalytical detection have enabled powerful laboratory assays such as enzyme-linked immunosorbent assay (ELISA) to be conducted in field-use lab-on-a-chip devices. In this paper, we present a low-cost universal serial bus (USB)-interfaced mobile platform to perform microfluidic ELISA operations in detecting the presence and concentrations of BDE-47 (2,2',4,4'-tetrabromodiphenyl ether), an environmental contaminant found in our food supply with adverse health impact. Our point-of-care diagnostic device utilizes flexible interdigitated carbon black electrodes to convert electric current into a microfluidic pump via gas bubble expansion during electrolytic reaction. The micropump receives power from a mobile phone and transports BDE-47 analytes through the microfluidic device conducting competitive ELISA. Using variable domain of heavy chain antibodies (commonly referred to as single domain antibodies or Nanobodies), the proposed device is sensitive for a BDE-47 concentration range of 10(-3)-10(4 ) µg/l, with a comparable performance to that uses a standard competitive ELISA protocol. It is anticipated that the potential impact in mobile detection of health and environmental contaminants will prove beneficial to our community and low-resource environments.

Racial disparities in the use of cardiac revascularization: does local hospital capacity matter?

OBJECTIVE: To assess the extent to which the observed racial disparities in cardiac revascularization use can be explained by the variation across counties where patients live, and how the within-county racial disparities is associated with the local hospital capacity. DATA SOURCES: Administrative data from Pennsylvania Health Care Cost Containment Council (PHC4) between 1995 and 2006. STUDY DESIGN: The study sample included 207,570 Medicare patients admitted to hospital for acute myocardial infarction (AMI). We identified the use of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) procedures within three months after the patient's initial admission for AMI. Multi-level hierarchical models were used to determine the extent to which racial disparities in procedure use were attributable to the variation in local hospital capacity. PRINCIPAL FINDINGS: Blacks were less likely than whites to receive CABG (9.1% vs. 5.8%; p<0.001) and PCI (15.7% vs. 14.2%; p<0.001). The state-level racial disparity in use rate decreases for CABG, and increases for PCI, with the county adjustment. Higher number of revascularization hospitals per 1,000 AMI patients was associated with smaller within-county racial differences in CABG and PCI rates. Meanwhile, very low capacity of catheterization suites and AMI hospitals contributed to significantly wider racial gap in PCI rate. CONCLUSIONS: County variation in cardiac revascularization use rates helps explain the observed racial disparities. While smaller hospital capacity is associated with lower procedure rates for both racial groups, the impact is found to be larger on blacks. Therefore, consequences of fewer medical resources may be particularly pronounced for blacks, compared with whites.

Reconfigurable microfluidics combined with antibody microarrays for enhanced detection of T-cell secreted cytokines.

Cytokines are small proteins secreted by leukocytes in blood in response to infections, thus offering valuable diagnostic information. Given that the same cytokines may be produced by different leukocyte subsets in blood, it is beneficial to connect production of cytokines to specific cell types. In this paper, we describe integration of antibody (Ab) microarrays into a microfluidic device to enable enhanced cytokine detection. The Ab arrays contain spots specific to cell-surface antigens as well as anti-cytokine detection spots. Infusion of blood into a microfluidic device results in the capture of specific leukocytes (CD4 T-cells) and is followed by detection of secreted cytokines on the neighboring Ab spots using sandwich immunoassay. The enhancement of cytokine signal comes from leveraging the concept of reconfigurable microfluidics. A three layer polydimethylsiloxane microfluidic device is fabricated so as to contain six microchambers (1 mm × 1 mm × 30 µm) in the ceiling of the device. Once the T-cell capture is complete, the device is reconfigured by withdrawing liquid from the channel, causing the chambers to collapse onto Ab arrays and enclose cell/anti-cytokine spots within a 30 nl volume. In a set of proof-of-concept experiments, we demonstrate that ∼90% pure CD4 T-cells can be captured inside the device and that signals for three important T-cell secreted cytokines, tissue necrosis factor-alpha, interferon-gamma, and interleukin-2, may be enhanced by 2 to 3 folds through the use of reconfigurable microfluidics.

Three-dimensional fit-to-flow microfluidic assembly.

Three-dimensional microfluidics holds great promise for large-scale integration of versatile, digitalized, and multitasking fluidic manipulations for biological and clinical applications. Successful translation of microfluidic toolsets to these purposes faces persistent technical challenges, such as reliable system-level packaging, device assembly and alignment, and world-to-chip interface. In this paper, we extended our previously established fit-to-flow (F2F) world-to-chip interconnection scheme to a complete system-level assembly strategy that addresses the three-dimensional microfluidic integration on demand. The modular F2F assembly consists of an interfacial chip, pluggable alignment modules, and multiple monolithic layers of microfluidic channels, through which convoluted three-dimensional microfluidic networks can be easily assembled and readily sealed with the capability of reconfigurable fluid flow. The monolithic laser-micromachining process simplifies and standardizes the fabrication of single-layer pluggable polymeric modules, which can be mass-produced as the renowned Lego(®) building blocks. In addition, interlocking features are implemented between the plug-and-play microfluidic chips and the complementary alignment modules through the F2F assembly, resulting in facile and secure alignment with average misalignment of 45 µm. Importantly, the 3D multilayer microfluidic assembly has a comparable sealing performance as the conventional single-layer devices, providing an average leakage pressure of 38.47 kPa. The modular reconfigurability of the system-level reversible packaging concept has been demonstrated by re-routing microfluidic flows through interchangeable modular microchannel layers.

Fit-to-Flow (F2F) interconnects: universal reversible adhesive-free microfluidic adaptors for lab-on-a-chip systems.

World-to-chip (macro-to-micro) interface continues to be one of the most complicated, ineffective, and unreliable components in the development of emerging lab-on-a-chip systems involving integrated microfluidic operations. A number of irreversible (e.g., adhesive gluing) and reversible techniques (e.g., press fitting) have attempted to provide dedicated fluidic passage from standard tubing to miniature on-chip devices, none of which completely addresses the above concerns. In this paper, we present standardized adhesive-free microfluidic adaptors, referred to as Fit-to-Flow (F2F) Interconnects, to achieve reliable hermetic seal, high-density tube packing, self-aligned plug-in, reworkable connectivity, straightforward scalability and expandability, and applicability to broad lab-on-a-chip platforms; analogous to the modular plug-and-play USB architecture employed in modern electronics. Specifically, two distinct physical packaging mechanisms are applied, with one utilizing induced tensile stress in elastomeric socket to establish reversible seal and the other using negative pressure to provide on demand vacuum shield, both of which can be adapted to a variety of experimental configurations. The non-leaking performance (up to 336 kPa) along with high tube-packing density (of 1 tube/mm(2)) and accurate self-guided alignment (of 10 µm) have been characterized. In addition, a 3D microfluidic mixer and a 6-level chemical gradient generator paired with the corresponding F2F Interconnects have been devised to illustrate the applicability of the universal fluidic connections to classic lab-on-a-chip operations.